Ada 2010 full
Upcoming SlideShare
Loading in...5
×
 

Ada 2010 full

on

  • 1,272 views

 

Statistics

Views

Total Views
1,272
Views on SlideShare
1,272
Embed Views
0

Actions

Likes
0
Downloads
4
Comments
0

0 Embeds 0

No embeds

Accessibility

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Ada 2010 full Ada 2010 full Document Transcript

    • P O S I T I O N S T A T E M E N TStandards of Medical Care in Diabetes—2010AMERICAN DIABETES ASSOCIATIOND iabetes is a chronic illness that re- more detailed information about manage- by the Executive Committee of ADA’s quires continuing medical care and ment of diabetes, refer to references 1–3. Board of Directors. ongoing patient self-management The recommendations included areeducation and support to prevent acute screening, diagnostic, and therapeutic ac- I. CLASSIFICATION ANDcomplications and to reduce the risk of tions that are known or believed to favor- DIAGNOSISlong-term complications. Diabetes care is ably affect health outcomes of patients A. Classificationcomplex and requires that many issues, with diabetes. A grading system (Table 1), The classification of diabetes includesbeyond glycemic control, be addressed. A developed by the American Diabetes As- four clinical classes:large body of evidence exists that sup- sociation (ADA) and modeled after exist-ports a range of interventions to improve ing methods, was used to clarify and ● type 1 diabetes (results from -cell de-diabetes outcomes. codify the evidence that forms the basis struction, usually leading to absolute These standards of care are intended for the recommendations. The level of ev- insulin deficiency)to provide clinicians, patients, research- idence that supports each recommenda- ● type 2 diabetes (results from a progres-ers, payors, and other interested individ- sive insulin secretory defect on the tion is listed after each recommendationuals with the components of diabetes background of insulin resistance) using the letters A, B, C, or E.care, general treatment goals, and tools to ● other specific types of diabetes due toevaluate the quality of care. While indi- These standards of care are revised annually by the ADA multidisciplinary other causes, e.g., genetic defects invidual preferences, comorbidities, and -cell function, genetic defects in insu-other patient factors may require modifi- Professional Practice Committee, and new evidence is incorporated. Members lin action, diseases of the exocrine pan-cation of goals, targets that are desirable creas (such as cystic fibrosis), and drug-for most patients with diabetes are pro- of the Professional Practice Committee or chemical-induced diabetes (such asvided. These standards are not intended and their disclosed conflicts of interest are in the treatment of AIDS or after organto preclude clinical judgment or more ex- listed in the Introduction. Subsequently, transplantation)tensive evaluation and management of the as with all position statements, the stan- ● gestational diabetes mellitus (GDM)patient by other specialists as needed. For dards of care are reviewed and approved (diabetes diagnosed during pregnancy)● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●Originally approved 1988. Most recent review/revision October 2009. Some patients cannot be clearly classifiedDOI: 10.2337/dc10-S011 as having type 1 or type 2 diabetes. Clin-Abbreviations: ABI, ankle-brachial index; ACCORD, Action to Control Cardiovascular Risk in Diabetes; ADAG, A1C-Derived Average Glucose Trial; ADVANCE, Action in Diabetes and Vascular Disease: Pre- ical presentation and disease progression terax and Diamicron Modified Release Controlled Evaluation; ACE, angiotensin converting enzyme; ARB, vary considerably in both types of diabe- angiotensin receptor blocker; ACT-NOW, ACTos Now Study for the Prevention of Diabetes; BMI, body tes. Occasionally, patients who otherwise mass index; CBG, capillary blood glucose; CFRD, cystic fibrosis–related diabetes; CGM, continuous have type 2 diabetes may present with ke- glucose monitoring; CHD, coronary heart disease; CHF, congestive heart failure; CCM, chronic care toacidosis. Similarly, patients with type 1 model; CKD, chronic kidney disease; CMS, Centers for Medicare and Medicaid Services; CSII, continuous subcutaneous insulin infusion; CVD, cardiovascular disease; DASH, Dietary Approaches to Stop Hyper- diabetes may have a late onset and slow tension; DCCT, Diabetes Control and Complications Trial; DKA, diabetic ketoacidosis; DMMP, diabetes (but relentless) progression despite hav- medical management plan; DPN, distal symmetric polyneuropathy; DPP, Diabetes Prevention Program; ing features of autoimmune disease. Such DPS, Diabetes Prevention Study; DREAM, Diabetes Reduction Assessment with Ramipril and Rosiglita- difficulties in diagnosis may occur in chil- zone Medication; DRS, Diabetic Retinopathy Study; DSME, diabetes self-management education; DSMT, diabetes self-management training; eAG, estimated average glucose; eGFR, estimated glomerular filtration dren, adolescents, and adults. The true rate; ECG, electrocardiogram; EDIC, Epidemiology of Diabetes Interventions and Complications; ERP, diagnosis may become more obvious over education recognition program; ESRD, end-stage renal disease; ETDRS, Early Treatment Diabetic Reti- time. nopathy Study; FDA, Food and Drug Administration; FPG, fasting plasma glucose; GDM, gestational diabetes mellitus; GFR, glomerular filtration rate; HAPO, Hyperglycemia and Adverse Pregnancy Out- B. Diagnosis of diabetes comes; ICU, intensive care unit; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; Look AHEAD, Action for Health in Diabetes; MDRD, Modification of Diet in Renal Disease; MNT, medical Recommendations nutrition therapy; NDEP, National Diabetes Education Program; NGSP, National Glycohemoglobin Stan- For decades, the diagnosis of diabetes has dardization Program; NPDR, nonproliferative diabetic retinopathy; OGTT, oral glucose tolerance test; PAD, peripheral arterial disease; PCOS, polycystic ovarian syndrome; PDR, proliferative diabetic retinop- been based on plasma glucose (PG) crite- athy; PPG, postprandial plasma glucose; RAS, renin-angiotensin system; SMBG, self-monitoring of blood ria, either fasting PG (FPG) or 2-h 75-g glucose; STOP-NIDDM, Study to Prevent Non-Insulin Dependent Diabetes; SSI, sliding scale insulin; oral glucose tolerance test (OGTT) values. TZD, thiazolidinedione; UKPDS, U.K. Prospective Diabetes Study; VADT, Veterans Affairs Diabetes Trial; In 1997, the first Expert Committee on XENDOS, XENical in the prevention of Diabetes in Obese Subjects.© 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly the Diagnosis and Classification of Diabe- cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons. tes Mellitus revised the diagnostic criteria org/licenses/by-nc-nd/3.0/ for details. using the observed association betweencare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S11
    • Standards of Medical CareTable 1 —ADA evidence grading system for clinical practice recommendations be used (an updated list of A1C assays and whether abnormal hemoglobins impactLevel of them is available at www.ngsp.org/prog/evidence Description index3.html). For conditions with abnor- mal red cell turnover, such as pregnancy orA Clear evidence from well-conducted, generalizable, randomized controlled trials that anemias from hemolysis and iron defi- are adequately powered, including: ciency, the diagnosis of diabetes must use ● Evidence from a well-conducted multicenter trial glucose criteria exclusively. ● Evidence from a meta-analysis that incorporated quality ratings in the analysis The established glucose criteria for Compelling nonexperimental evidence, i.e., all or none rule developed by Center the diagnosis of diabetes (FPG and 2-h for Evidence Based Medicine at Oxford PG) remain valid. Patients with severe hy- Supportive evidence from well-conducted randomized controlled trials that are perglycemia such as those who present adequately powered, including: with severe classic hyperglycemic symp- ● Evidence from a well-conducted trial at one or more institutions toms or hyperglycemic crisis can continue ● Evidence from a meta-analysis that incorporated quality ratings in the analysis to be diagnosed when a random (or ca-B Supportive evidence from well-conducted cohort studies: sual) PG of 200 mg/dl (11.1 mmol/l) is ● Evidence from a well-conducted prospective cohort study or registry found. It is likely that in such cases the ● Evidence from a well-conducted meta-analysis of cohort studies health care professional would also con- Supportive evidence from a well-conducted case-control study duct an A1C test as part of the initial as-C Supportive evidence from poorly controlled or uncontrolled studies sessment of the severity of the diabetes ● Evidence from randomized clinical trials with one or more major or three or and that it would be above the diagnostic more minor methodological flaws that could invalidate the results cut point. However, in rapidly evolving ● Evidence from observational studies with high potential for bias (such as case diabetes such as the development of type series with comparison to historical controls) 1 in some children, the A1C may not be ● Evidence from case series or case reports significantly elevated despite frank Conflicting evidence with the weight of evidence supporting the recommendation diabetes.E Expert consensus or clinical experience Just as there is 100% concordance between the FPG and 2-h PG tests, there is not perfect concordance between A1Cglucose levels and presence of retinopa- the A1C test to diagnose diabetes with a and either glucose-based test. Analyses ofthy as the key factor with which to iden- threshold of 6.5%, and ADA affirms this National Health and Nutrition Examina-tify threshold FPG and 2-h PG levels. The decision (6). The diagnostic test should tion Survey (NHANES) data indicate that,committee examined data from three be performed using a method certified by assuming universal screening of the undi-cross-sectional epidemiologic studies that the National Glycohemoglobin Standard- agnosed, the A1C cut point of 6.5%assessed retinopathy with fundus photog- ization Program (NGSP) and standard- identifies one-third fewer cases of undiag-raphy or direct ophthalmoscopy and ized or traceable to the Diabetes Control nosed diabetes than a fasting glucose cutmeasured glycemia as FPG, 2-h PG, and and Complications Trial (DCCT) refer- point of 126 mg/dl (7.0 mmol/l) (E.HbA1c (A1C). The studies demonstrated ence assay. Point-of-care A1C assays are Gregg, personal communication). How-glycemic levels below which there was lit- not sufficiently accurate at this time to use ever, in practice, a large portion of thetle prevalent retinopathy and above for diagnostic purposes. diabetic population remains unaware ofwhich the prevalence of retinopathy in- Epidemiologic datasets show a rela- their condition. Thus, the lower sensitiv-creased in an apparently linear fashion. tionship between A1C and the risk of ret- ity of A1C at the designated cut point mayThe deciles of FPG, 2-h PG, and A1C at inopathy similar to that which has been well be offset by the test’s greater practi-which retinopathy began to increase were shown for corresponding FPG and 2-h PG cality, and wider application of a morethe same for each measure within each thresholds. The A1C has several advan- convenient test (A1C) may actually in-population. The analyses helped to in- tages to the FPG, including greater conve- crease the number of diagnoses made.form a then-new diagnostic cut point of nience, since fasting is not required; As with most diagnostic tests, a test 126 mg/dl (7.0 mmol/l) for FPG and evidence to suggest greater preanalytical result diagnostic of diabetes should be re-confirmed the long-standing diagnostic stability; and less day-to-day perturba- peated to rule out laboratory error, unless2-h PG value of 200 mg/dl (11.1 tions during periods of stress and illness. the diagnosis is clear on clinical grounds,mmol/l) (4). These advantages must be balanced by such as a patient with classic symptoms of ADA has not previously recom- greater cost, limited availability of A1C hyperglycemia or hyperglycemic crisis. Itmended the use of A1C for diagnosing testing in certain regions of the develop- is preferable that the same test be repeateddiabetes, in part due to lack of standard- ing world, and incomplete correlation be- for confirmation, since there will be aization of the assay. However, A1C assays tween A1C and average glucose in certain greater likelihood of concurrence in thisare now highly standardized, and their re- individuals. In addition, the A1C can be case. For example, if the A1C is 7.0% andsults can be uniformly applied both tem- misleading in patients with certain forms a repeat result is 6.8%, the diagnosis ofporally and across populations. In a of anemia and hemoglobinopathies. For diabetes is confirmed. However, there arerecent report (5), after an extensive review patients with a hemoglobinopathy but scenarios in which results of two differentof both established and emerging epide- normal red cell turnover, such as sickle tests (e.g., FPG and A1C) are available formiological evidence, an international ex- cell trait, an A1C assay without interfer- the same patient. In this situation, if thepert committee recommended the use of ence from abnormal hemoglobins should two different tests are both above the di-S12 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementTable 2—Criteria for the diagnosis of diabetes costs of false positives (falsely identifying1. A1C 6.5%. The test should be performed in a laboratory using a method and then spending intervention resources that is NGSP certified and standardized to the DCCT assay.* on those who were not going to develop OR diabetes anyway).2. FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at Linear regression analyses of nation- least 8 h.* ally representative U.S. data (NHANES OR 2005–2006) indicate that among the3. Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT. nondiabetic adult population, an FPG of The test should be performed as described by the World Health 110 mg/dl corresponds to an A1C of Organization, using a glucose load containing the equivalent of 75 g 5.6%, while an FPG of 100 mg/dl corre- anhydrous glucose dissolved in water.* sponds to an A1C of 5.4%. Receiver op- OR erating curve analyses of these data4. In a patient with classic symptoms of hyperglycemia or hyperglycemic indicate that an A1C value of 5.7%, com- crisis, a random plasma glucose 200 mg/dl (11.1 mmol/l). pared with other cut points, has the best combination of sensitivity (39%) and*In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing. specificity (91%) to identify cases of IFG (FPG 100 mg/dl [5.6 mmol/l]) (R.T.agnostic threshold, the diagnosis of dia- or impaired glucose tolerance (IGT) (2-h Ackerman, Personal Communication).betes is confirmed. OGTT values of 140 mg/dl [7.8 mmol/l] Other analyses suggest that an A1C of On the other hand, if two different to 199 mg/dl [11.0 mmol/l]). 5.7% is associated with diabetes risk sim-tests are available in an individual and the Individuals with IFG and/or IGT have ilar to that of the high-risk participants inresults are discordant, the test whose re- been referred to as having pre-diabetes, the Diabetes Prevention Program (DPP)sult is above the diagnostic cut point indicating the relatively high risk for the (R.T. Ackerman, personal communica-should be repeated, and the diagnosis is future development of diabetes. IFG and tion). Hence, it is reasonable to considermade on the basis of the confirmed test. IGT should not be viewed as clinical en- an A1C range of 5.7– 6.4% as identifyingThat is, if a patient meets the diabetes cri- tities in their own right but rather risk individuals with high risk for future dia-terion of the A1C (two results 6.5%) but factors for diabetes as well as cardiovas- betes and to whom the term pre-diabetesnot the FPG ( 126 mg/dl or 7.0 mmol/l), cular disease (CVD). IFG and IGT are may be applied (6).or vice versa, that person should be con- associated with obesity (especially As is the case for individuals found tosidered to have diabetes. Admittedly, in abdominal or visceral obesity), dyslipide- have IFG and IGT, individuals with anmost circumstance the “nondiabetic” test mia with high triglycerides and/or low A1C of 5.7– 6.4% should be informed ofis likely to be in a range very close to the HDL cholesterol, and hypertension. their increased risk for diabetes as wellthreshold that defines diabetes. Structured lifestyle intervention, aimed at as CVD and counseled about effective Since there is preanalytic and analytic increasing physical activity and produc- strategies to lower their risks (see IV. PRE-variability of all the tests, it is also possible ing 5–10% loss of body weight, and cer- VENTION/DELAY OF TYPE 2 DIABETES).that when a test whose result was above tain pharmacological agents have been As with glucose measurements, the contin-the diagnostic threshold is repeated, the demonstrated to prevent or delay the de- uum of risk is curvilinear, so that as A1Csecond value will be below the diagnostic velopment of diabetes in people with IGT rises, the risk of diabetes rises dispropor-cut point. This is least likely for A1C, (see Table 7). It should be noted that the tionately. Accordingly, interventionssomewhat more likely for FPG, and most 2003 ADA Expert Committee report re- should be most intensive and follow-uplikely for the 2-h PG. Barring a laboratory duced the lower FPG cut point to define should be particularly vigilant for thoseerror, such patients are likely to have test IFG from 110 mg/dl (6.1 mmol/l) to 100 with an A1C 6.0%, who should be con-results near the margins of the threshold mg/dl (5.6 mmol/l), in part to make the sidered to be at very high risk. However,for a diagnosis. The healthcare profes- prevalence of IFG more similar to that of just as an individual with a fasting glucose ofsional might opt to follow the patient IGT. However, the World Health Organi- 98 mg/dl (5.4 mmol/l) may not be at negli-closely and repeat the testing in 3– 6 zation (WHO) and many other diabetes gible risk for diabetes, individuals with anmonths. organizations did not adopt this change. A1C 5.7% may still be at risk, depending The current diagnostic criteria for di- As the A1C becomes increasingly on the level of A1C and presence of otherabetes are summarized in Table 2. used to diagnose diabetes in individuals risk factors, such as obesity and family with risk factors, it will also identify those history.C. Categories of increased risk for at high risk for developing diabetes in thediabetes future. As was the case with the glucose Table 3—Categories of increased risk forIn 1997 and 2003, The Expert Committee measures, defining a lower limit of an in- diabetes*on the Diagnosis and Classification of Di- termediate category of A1C is somewhat FPG 100–125 mg/dl (5.6–6.9 mmol/l)abetes Mellitus (4,7) recognized an inter- arbitrary, since risk of diabetes with any IFGmediate group of individuals whose measure or surrogate of glycemia is a con- 2-h PG on the 75-g OGTT 140–199 mg/dlglucose levels, although not meeting cri- tinuum extending well into the normal (7.8–11.0 mmol/l) IGTteria for diabetes, are nevertheless too ranges. To maximize equity and efficiency A1C 5.7–6.4%high to be considered normal. This group of preventive interventions, such an A1C *For all three tests, risk is continuous, extendingwas defined as having impaired fasting cut point, should balance the costs of false below the lower limit of the range and becomingglucose (IFG) (FPG levels of 100 mg/dl negatives (failing to identify those who are disproportionately greater at higher ends of the[5.6 mmol/l] to 125 mg/dl [6.9 mmol/l]) going to develop diabetes) against the range.care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S13
    • Standards of Medical CareTable 4—Criteria for testing for diabetes in asymptomatic adult individuals Recommendations for testing for dia-1. 2 Testing should be considered in all adults who are overweight (BMI 25 kg/m *) and betes in asymptomatic undiagnosed have additional risk factors: adults are listed in Table 4. Testing should ● physical inactivity be considered in adults of any age with ● first-degree relative with diabetes BMI 25 kg/m2 and one or more risk fac- ● members of a high-risk ethnic population (e.g., African American, Latino, Native tors for diabetes. Because age is a major American, Asian American, Pacific Islander) risk factor for diabetes, testing of those ● women who delivered a baby weighing 9 lb or were diagnosed with GDM without other risk factors should begin no ● hypertension ( 140/90 mmHg or on therapy for hypertension) later than at age 45 years. ● HDL cholesterol level 35 mg/dl (0.90 mmol/l) and/or a triglyceride level 250 Either A1C, FPG, or 2-h OGTT is ap- mg/dl (2.82 mmol/l) propriate for testing. The 2-h OGTT identi- ● women with polycystic ovary syndrome fies people with either IFG or IGT and thus ● A1C 5.7%, IGT, or IFG on previous testing more people at increased risk for the devel- ● other clinical conditions associated with insulin resistance (e.g., severe obesity, opment of diabetes and CVD. It should be acanthosis nigricans) noted that the two tests do not necessarily ● history of CVD detect the same individuals (10). The effi-2. In the absence of the above criteria, testing diabetes should begin at age 45 years cacy of interventions for primary preven-3. If results are normal, testing should be repeated at least at 3-year intervals, with tion of type 2 diabetes (11–17) has consideration of more frequent testing depending on initial results and risk primarily been demonstrated among indi- status. viduals with IGT, but not for individuals with IFG (who do not also have IGT) or*At-risk BMI may be lower in some ethnic groups. those with specific A1C levels. The appropriate interval between Table 3 summarizes the categories of who the provider tests because of high tests is not known (18). The rationale forincreased risk for diabetes. suspicion of diabetes, to the symptomatic the 3-year interval is that false negatives patient. The discussion herein is primar- will be repeated before substantial timeII. TESTING FOR DIABETES ily framed as testing for diabetes in indi- elapses, and there is little likelihood thatIN ASYMPTOMATIC viduals without symptoms. Testing for an individual will develop significantPATIENTS diabetes will also detect individuals at in- complications of diabetes within 3 years creased future risk for diabetes, herein re- of a negative test result.Recommendations ferred to as pre-diabetic. Because of the need for follow-up and● Testing to detect type 2 diabetes and discussion of abnormal results, testing assess risk for future diabetes in asymp- A. Testing for type 2 diabetes and should be carried out within the health tomatic people should be considered in risk of future diabetes in adults care setting. Community screening out- adults of any age who are overweight or Type 2 diabetes is frequently not diag- side a health care setting is not recom- obese (BMI 25 kg/m2) and who have nosed until complications appear, and mended because people with positive one or more additional risk factors for approximately one-fourth of all people tests may not seek, or have access to, ap- diabetes (Table 4). In those without with diabetes in the U.S. may be undiag- propriate follow-up testing and care. these risk factors, testing should begin nosed. Although the effectiveness of early Conversely, there may be failure to ensure at age 45 years. (B) identification of pre-diabetes and diabetes appropriate repeat testing for individuals● If tests are normal, repeat testing should through mass testing of asymptomatic in- who test negative. Community screening be carried out at least at 3-year inter- dividuals has not been proven definitively may also be poorly targeted, i.e., it may vals. (E) (and rigorous trials to provide such proof fail to reach the groups most at risk and● To test for diabetes or to assess risk of are unlikely to occur), pre-diabetes and inappropriately test those at low risk (the future diabetes, either A1C, FPG , or diabetes meet established criteria for con- worried well) or even those already diag- 2-h 75-g OGTT are appropriate. (B) ditions in which early detection is appro- nosed (19,20).● In those identified with increased risk priate. Both conditions are common, are for future diabetes, identify and, if ap- increasing in prevalence, and impose sig- propriate, treat other CVD risk factors. nificant public health burdens. There is a B. Testing for type 2 diabetes in (B) long presymptomatic phase before the di- children agnosis of type 2 diabetes is usually made. The incidence of type 2 diabetes in ado-For many illnesses there is a major dis- Relatively simple tests are available to de- lescents has increased dramatically in thetinction between screening and diagnos- tect preclinical disease (9). Additionally, last decade, especially in minority popu-tic testing. However, for diabetes the same the duration of glycemic burden is a lations (21), although the disease remainstests would be used for “screening” as for strong predictor of adverse outcomes, rare in the general pediatric populationdiagnosis. Type 2 diabetes has a long and effective interventions exist to pre- (22). Consistent with recommendationsasymptomatic phase and significant clin- vent progression of pre-diabetes to diabe- for adults, children and youth at in-ical risk markers. Diabetes may be identi- tes (see IV. PREVENTION/DELAY OF creased risk for the presence or the devel-fied anywhere along a spectrum of clinical TYPE 2 DIABETES) and to reduce risk of opment of type 2 diabetes should bescenarios ranging from a seemingly low- complications of diabetes (see VI. PRE- tested within the health care setting (23).risk individual who happens to have glu- VENTION AND MANAGEMENT OF DI- The recommendations of the ADA con-cose testing, to a higher-risk individual ABETES COMPLICATIONS). sensus statement on type 2 diabetes inS14 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementTable 5—Testing for type 2 diabetes in asymptomatic children within ranges previously considered nor-Criteria: Overweight (BMI 85th percentile for age and sex, weight for height mal for pregnancy. For most complica- 85th percentile, or weight 120% of ideal for height) tions there was no threshold for risk.Plus any two of ● Family history of type 2 diabetes in first- or second-degree relative These results have led to careful reconsid- the following ● Race/ethnicity (Native American, African American, Latino, Asian eration of the diagnostic criteria for GDM. risk factors: American, Pacific Islander) The IADPSG recommended that all ● Signs of insulin resistance or conditions associated with insulin women not known to have prior diabetes resistance (acanthosis nigricans, hypertension, dyslipidemia, undergo a 75-g OGTT at 24 –28 weeks of polycystic ovary syndrome, or small for gestational age gestation. The group developed diagnos- birthweight) tic cut points for the fasting, 1-h, and 2-h ● Maternal history of diabetes or GDM during the child’s gestation PG measurements that conveyed an oddsAge of Age 10 years or at onset of puberty, if puberty occurs at a younger ratio for adverse outcomes of at least 1.75 initiation: age compared with women with the meanFrequency: Every 3 years glucose levels in the HAPO study. At the time of this update to the Stan- dards of Medical Care in Diabetes, ADA ischildren and youth, with some modifica- set or first recognition during pregnancy planning to work with U.S. obstetrical or-tions, are summarized in Table 5. (4). Although most cases resolve with de- ganizations to consider adoption of the livery, the definition applied whether the IADPSG diagnostic criteria and to discussC. Screening for type 1 diabetes condition persisted after pregnancy and the implications of this change. While thisGenerally, people with type 1 diabetes did not exclude the possibility that unrec- change will significantly increase thepresent with acute symptoms of diabetes ognized glucose intolerance may have an- prevalence of GDM, there is mounting ev-and markedly elevated blood glucose lev- tedated or begun concomitantly with the idence that treating even mild GDM re-els, and most cases are diagnosed soon pregnancy. This definition facilitated a duces morbidity for both mother andafter the onset of hyperglycemia. How- uniform strategy for detection and classi- baby (27).ever, evidence from type 1 diabetes pre- fication of GDM, but its limitations were Because women with a history ofvention studies suggests that measurement recognized for many years. As the ongo- GDM have a greatly increased subsequentof islet autoantibodies identifies individ- ing epidemic of obesity and diabetes has risk for diabetes (28), they should beuals who are at risk for developing type 1 led to more type 2 diabetes in women of screened for diabetes 6 –12 weeks post-diabetes. Such testing may be appropriate childbearing age, the number of pregnant partum, using nonpregnant OGTT crite-in high-risk individuals, such as those women with undiagnosed type 2 diabetes ria, and should be followed up withwith prior transient hyperglycemia or has increased (24). After deliberations in subsequent screening for the develop-those who have relatives with type 1 dia- 2008 –2009, the International Associa- ment of diabetes or pre-diabetes, as out-betes, in the context of clinical research tion of Diabetes and Pregnancy Study lined in II. TESTING FOR DIABETES INstudies (see, for example, http://www2. Groups (IADPSG), an international con- ASYMPTOMATIC PATIENTS. Informa-diabetestrialnet.org). Widespread clini- sensus group with representatives from tion on the National Diabetes Educationcal testing of asymptomatic low-risk multiple obstetrical and diabetes organi- Program (NDEP) campaign to preventindividuals cannot currently be recom- zations, including ADA, recommended type 2 diabetes in women with GDM canmended, as it would identify very few in- that high-risk women found to have dia- be found at http://ndep.nih.gov/media/dividuals in the general population who betes at their initial prenatal visit using NeverTooEarly_Tipsheet.pdf.are at risk. Individuals who screen posi- standard criteria (Table 2) receive a diag-tive should be counseled about their risk nosis of overt, not gestational, diabetes. IV. PREVENTION/DELAYof developing diabetes. Clinical studies Approximately 7% of all pregnancies OF TYPE 2 DIABETESare being conducted to test various meth- (ranging from 1 to 14% depending on theods of preventing type 1 diabetes or re- population studied and the diagnostic Recommendationsversing early type 1 diabetes in those with tests used) are complicated by GDM, re- ● Patients with IGT (A), IFG (E), or anevidence of autoimmunity. sulting in more than 200,000 cases A1C of 5.7– 6.4% (E) should be re- annually. ferred to an effective ongoing supportIII. DETECTION AND Because of the risks of GDM to the program for weight loss of 5–10% ofDIAGNOSIS OF GDM mother and neonate, screening and diag- body weight and an increase in physical nosis are warranted. Current screening activity of at least 150 min/week ofRecommendations and diagnostic strategies, based on the moderate activity such as walking.● Screen for GDM using risk factor anal- 2004 ADA position statement on GDM ● Follow-up counseling appears to be im- ysis and, if appropriate, an OGTT. (C) (25), are outlined in Table 6. portant for success. (B)● Women with GDM should be screened Results of the Hyperglycemia and Ad- ● Based on potential cost savings of dia- for diabetes 6 –12 weeks postpartum verse Pregnancy Outcomes (HAPO) study betes prevention, such counseling and should be followed up with subse- (26), a large-scale ( 25,000 pregnant should be covered by third-party pay- quent screening for the development of women) multinational epidemiologic ors. (E) diabetes or pre-diabetes. (E) study, demonstrated that risk of adverse ● In addition to lifestyle counseling, met- maternal, fetal, and neonatal outcomes formin may be considered in those whoFor many years, GDM has been defined as continuously increased as a function of are at very high risk for developing di-any degree of glucose intolerance with on- maternal glycemia at 24 –28 weeks, even abetes (combined IFG and IGT pluscare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S15
    • Standards of Medical CareTable 6—Screening for and diagnosis of GDM other drugs, the issues of cost, side effects,Carry out diabetes risk assessment at the first prenatal visit. and lack of persistence of effect in someWomen at very high risk should be screened for diabetes as soon as possible after the studies led the panel to not recommend confirmation of pregnancy. Criteria for very high risk are: use for diabetes prevention. Metformin ● Severe obesity use was recommended only for very- ● Prior history of GDM or delivery of large-for-gestational-age infant high-risk individuals (those with com- ● Presence of glycosuria bined IGT and IFG who are obese and ● Diagnosis of PCOS have at least one other risk factor for dia- ● Strong family history of type 2 diabetes betes) who are under 60 years of age. InScreening/diagnosis at this stage of pregnancy should use standard diagnostic testing (Table addition, the panel highlighted the evi- 2). dence that in the DPP, metformin wasAll women of greater than low risk of GDM, including those above not found to have diabetes most effective compared with lifestyle in early in pregnancy, should undergo GDM testing at 24–28 weeks of gestation. Low- individuals with BMI 35 kg/m2 and risk status, which does not require GDM screening, is defined as women with ALL of those under age 60 years. the following characteristics: ● Age 25 years V. DIABETES CARE ● Weight normal before pregnancy ● Member of an ethnic group with a low prevalence of diabetes A. Initial evaluation ● No known diabetes in first-degree relatives A complete medical evaluation should be ● No history of abnormal glucose tolerance performed to classify the diabetes, detect ● No history of poor obstetrical outcome the presence of diabetes complications,Two approaches may be followed for GDM screening at 24–28 weeks: review previous treatment and glycemic 1. Two-step approach: control in patients with established diabe- A. Perform initial screening by measuring plasma or serum glucose 1 h after a 50-g load tes, assist in formulating a management of 140 mg/dl identifies 80% of women with GDM, while the sensitivity is further plan, and provide a basis for continuing increased to 90% by a threshold of 130 mg/dl. care. Laboratory tests appropriate to the B. Perform a diagnostic 100-g OGTT on a separate day in women who exceed the chosen evaluation of each patient’s medical con- threshold on 50-g screening. dition should be performed. A focus on 2. One-step approach (may be preferred in clinics with high prevalence of GDM): Perform the components of comprehensive care a diagnostic 100-g OGTT in all women to be tested at 24–28 weeks. (Table 8) will assist the health care team to The 100-g OGTT should be performed in the morning after an overnight fast of at least 8 ensure optimal management of the pa- h. tient with diabetes.To make a diagnosis of GDM, at least two of the following plasma glucose values must be found: B. Management ● Fasting 95 mg/dl People with diabetes should receive med- ● 1-h 180 mg/dl ical care from a physician-coordinated ● 2-h 155 mg/dl team. Such teams may include, but are ● 3-h 140 mg/dl not limited to, physicians, nurse practitio- ners, physician’s assistants, nurses, dieti- tians, pharmacists, and mental health other risk factors such as A1C 6%, been shown to decrease incident diabetes professionals with expertise and a special hypertension, low HDL cholesterol, el- to various degrees. A summary of major interest in diabetes. It is essential in this evated triglycerides, or family history of diabetes prevention trials is shown in Ta- collaborative and integrated team ap- diabetes in a first-degree relative) and ble 7. proach that individuals with diabetes as- who are obese and under 60 years of Two studies of lifestyle intervention sume an active role in their care. age. (E) have shown persistent reduction in the The management plan should be for-● Monitoring for the development of di- role of conversion to type 2 diabetes with mulated as a collaborative therapeutic al- abetes in those with pre-diabetes 3 years (29) to 14 years (30) of postinter- liance among the patient and family, the should be performed every year. (E) vention follow-up. physician, and other members of the Based on the results of clinical trials health care team. A variety of strategiesRandomized controlled trials have shown and the known risks of progression of and techniques should be used to providethat individuals at high risk for develop- pre-diabetes to diabetes, an ADA Consen- adequate education and development ofing diabetes (those with IFG, IGT, or sus Development Panel (36) concluded problem-solving skills in the various as-both) can be given interventions that sig- that people with IGT and/or IFG should pects of diabetes management. Imple-nificantly decrease the rate of onset of di- be counseled on lifestyle changes with mentation of the management planabetes (11–17). These interventions goals similar to those of the DPP (5–10% requires that each aspect is understoodinclude intensive lifestyle modification weight loss and moderate physical activ- and agreed to by the patient and the careprograms that have been shown to be very ity of 30 min/day). Regarding the more providers and that the goals and treat-effective (58% reduction after 3 years) difficult issue of drug therapy for diabetes ment plan are reasonable. Any planand use of the pharmacologic agents met- prevention, the consensus panel felt that should recognize diabetes self-manage-formin, -glucosidase inhibitors, orlistat, metformin should be the only drug con- ment education (DSME) and on-going di-and thiazolidinediones, each of which has sidered for use in diabetes prevention. For abetes support as an integral componentS16 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementTable 7—Therapies proven effective in diabetes prevention trials Incidence in 3-Year Mean control Relative risk number age Duration Intervention subjects reduction (%) needed toStudy (ref.) n Population (years) (years) (daily dose) (%/year) (95% CI) treat*Lifestyle Finnish DPS (12) 522 IGT, BMI 25 kg/m2 55 3.2 I-D&E 6 58 (30–70) 8.5 DPP (11) 2,161† IGT, BMI 24 kg/m2, 51 3 I-D&E 10.4 58 (48–66) 6.9 FPG 5.3 mmol/l Da Qing (13) 259† IGT (randomized 45 6 G-D&E 14.5 38 (14–56) 7.9 groups) Toranomon Study (31) 458 IGT (men), BMI 24 55 4 I-D&E 2.4 67 (P 0.043)‡ 20.6 kg/m2 Indian DPP (17) 269† IGT 46 2.5 I-D&E 23 29 (21–37) 6.4Medications DPP (11) 2,155† IGT, BMI 24 kg/m2, 51 2.8 Metformin 10.4 31 (17–43) 13.9 FPG 5.3 mmol/l (1,700 mg) Indian DPP (17) 269† IGT 46 2.5 Metformin 23 26 (19–35) 6.9 (500 mg) STOP NIDDM (15) 1,419 IGT, FPG 5.6 54 3.2 Acarbose 12.4 25 (10–37) 9.6 mmol/l (300 mg) XENDOS (32) 3,277 BMI 30 kg/m2 43 4 Orlistat (360 2.4 37 (14–54) 45.5 mg) DREAM (16) 5,269 IGT or IFG 55 3.0 Rosiglitazone 9.1 60 (54–65) 6.9 (8 mg) Voglibose Ph-3 (33) 1,780 IGT 56 3.0 (1-year Rx) Vogliobose 12.0 40 (18–57) 21 (1-year (0.2 mg) Rx) ACT-NOW (34) 602 IGT or IFG 52 2.6 Pioglitizone 6.8 81 (61–91) 6.3 (45 mg)Modified and reprinted with permission (35). Percentage points: *Number needed to treat to prevent 1 case of diabetes, standardized for a 3-year period to improvecomparisons across studies. †Number of participants in the indicated comparisons, not necessarily in entire study. ‡Calculated from information in the article.ACT-NOW, ACTos Now Study for the Prevention of Diabetes; DPP, Diabetes Prevention Program; DPS, Diabetes Prevention Study; DREAM, Diabetes ReductionAssessment with Ramipril and Rosiglitazone Medication; STOP NIDDM, Study to Prevent Non-Insulin Dependent Diabetes; XENDOS, Xenical in the prevention ofDiabetes in Obese Subjects. I, individual; G, group; D&E, diet and exercise.of care. In developing the plan, consider- tiple insulin injections or insulin pump adherence to ongoing use of the device.ation should be given to the patient’s age, therapy. (A) (C)school or work schedule and conditions, ● For patients using less frequent insulin ● CGM may be a supplemental tool tophysical activity, eating patterns, social injections, noninsulin therapies, or SMBG in those with hypoglycemia un-situation and cultural factors, and pres- medical nutrition therapy (MNT) awareness and/or frequent hypoglyce-ence of complications of diabetes or other alone, SMBG may be useful as a guide to mic episodes. (E)medical conditions. the success of therapy. (E) ● To achieve postprandial glucose tar- The ADA consensus and position state-C. Glycemic control gets, postprandial SMBG may be appro- ments on SMBG provide a comprehensive priate. (E) review of the subject (37,38). Major clin- ● When prescribing SMBG, ensure that ical trials of insulin-treated patients that1. Assessment of glycemic control patients receive initial instruction in, demonstrated the benefits of intensiveTwo primary techniques are available for and routine follow-up evaluation of, glycemic control on diabetes complica-health providers and patients to assess the SMBG technique and using data to ad- tions have included SMBG as part ofeffectiveness of the management plan on just therapy. (E) multifactorial interventions, suggestingglycemic control: patient self-monitoring ● Continuous glucose monitoring (CGM) that SMBG is a component of effectiveof blood glucose (SMBG) or interstitial in conjunction with intensive insulin therapy. SMBG allows patients to eval-glucose and A1C. regimens can be a useful tool to lower uate their individual response to ther- A1C in selected adults (age 25 years) apy and assess whether glycemic targetsa. Glucose monitoring with type 1 diabetes (A). are being achieved. Results of SMBG can ● Although the evidence for A1C lower- be useful in preventing hypoglycemiaRecommendations ing is less strong in children, teens, and and adjusting medications (particularly● SMBG should be carried out three or younger adults, CGM may be helpful in prandial insulin doses), MNT, and more times daily for patients using mul- these groups. Success correlates with physical activity.care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S17
    • Standards of Medical CareTable 8—Components of the comprehensive diabetes evaluation strument and user dependent (43), it isMedical history important to evaluate each patient’s mon- ● Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding) itoring technique, both initially and at ● Eating patterns, physical activity habits, nutritional status, and weight history; growth regular intervals thereafter. In addition, and development in children and adolescents optimal use of SMBG requires proper in- ● Diabetes education history terpretation of the data. Patients should ● Review of previous treatment regimens and response to therapy (A1C records) be taught how to use the data to adjustCurrent treatment of diabetes, including medications, meal plan, physical activity patterns, food intake, exercise, or pharmacological and results of glucose monitoring and patient’s use of data therapy to achieve specific glycemic goals, ● DKA frequency, severity, and cause and these skills should be reevaluated ● Hypoglycemic episodes periodically. ● Hypoglycemia awareness CGM through the measurement of in- ● Any severe hypoglycemia: frequency and cause terstitial glucose (which correlates well ● History of diabetes-related complications with PG) is available. These sensors re- ● Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of quire calibration with SMBG, and the lat- foot lesions; autonomic, including sexual dysfunction and gastroparesis) ter are still recommended for making ● Macrovascular: CHD, cerebrovascular disease, PAD acute treatment decisions. CGM devices ● Other: psychosocial problems*, dental disease* also have alarms for hypo- and hypergly-Physical examination cemic excursions. Small studies in se- ● Height, weight, BMI lected patients with type 1 diabetes have ● Blood pressure determination, including orthostatic measurements when indicated suggested that CGM use reduces the time ● Fundoscopic examination* spent in hypo- and hyperglycemic ranges ● Thyroid palpation and may modestly improve glycemic con- ● Skin examination (for acanthosis nigricans and insulin injection sites) trol. A larger 26-week randomized trial of ● Comprehensive foot examination: 322 type 1 diabetic patients showed that ● Inspection adults age 25 years and older using inten- ● Palpation of dorsalis pedis and posterior tibial pulses sive insulin therapy and CGM experi- ● Presence/absence of patellar and Achilles reflexes enced a 0.5% reduction in A1C (from ● Determination of proprioception, vibration, and monofilament sensation 7.6 to 7.1%) compared with usual in-Laboratory evaluation tensive insulin therapy with SMBG (44). ● A1C, if results not available within past 2–3 months Sensor use in children, teens, and adults ● If not performed/available within past year: to age 24 years did not result in significant ● Fasting lipid profile, including total, LDL- and HDL cholesterol and triglycerides A1C lowering, and there was no signifi- ● Liver function tests cant difference in hypoglycemia in any ● Test for urine albumin excretion with spot urine albumin/creatinine ratio group. Importantly, the greatest predictor ● Serum creatinine and calculated GFR of A1C lowering in this study for all age- ● TSH in type 1 diabetes, dyslipidemia, or women over age 50 years groups was frequency of sensor use,Referrals which was lower in younger age-groups. ● Annual dilated eye exam In a smaller randomized controlled trial of ● Family planning for women of reproductive age 129 adults and children with baseline ● Registered dietitian for MNT A1C 7.0%, outcomes combining A1C ● DSME and hypoglycemia favored the group us- ● Dental examination ing CGM, suggesting that CGM is also ● Mental health professional, if needed beneficial for individuals with type 1 dia- betes who have already achieved excellent* See appropriate referrals for these categories. control with A1C 7.0% (45). Although CGM is an evolving technology, emerging The frequency and timing of SMBG clear. A meta-analysis of SMBG in non– data suggest that it may offer benefit inshould be dictated by the particular needs insulin-treated patients with type 2 appropriately selected patients who areand goals of the patient. SMBG is espe- diabetes concluded that some regimen of motivated to wear it most of the time.cially important for patients treated with SMBG was associated with a reduction in CGM may be particularly useful in thoseinsulin in order to monitor for and pre- A1C of 0.4%. However, many of the stud- with hypoglycemia unawareness and/orvent asymptomatic hypoglycemia and hy- ies in this analysis also included patient frequent episodes of hypoglycemia, andperglycemia. For most patients with type education with diet and exercise counsel- studies in this area are ongoing.1 diabetes and pregnant women taking ing and, in some cases, pharmacologic in-insulin, SMBG is recommended three or tervention, making it difficult to assess the b. A1Cmore times daily. For these populations, contribution of SMBG alone to improvedsignificantly more frequent testing may be control (39). Several recent trials have Recommendationsrequired to reach A1C targets safely with- called into question the clinical utility ● Perform the A1C test at least two timesout hypoglycemia. The optimal frequency and cost-effectiveness of routine SMBG in a year in patients who are meeting treat-and timing of SMBG for patients with type non–insulin-treated patients (40 – 42). ment goals (and who have stable glyce-2 diabetes on noninsulin therapy is un- Because the accuracy of SMBG is in- mic control). (E)S18 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement● Perform the A1C test quarterly in pa- Table 9—Correlation of A1C with average ant, clinicians should consider the possi- tients whose therapy has changed or glucose bilities of hemoglobinopathy or altered who are not meeting glycemic goals. (E) red cell turnover and the options of more● Use of point-of-care testing for A1C al- frequent and/or different timing of SMBG Mean plasma glucose lows for timely decisions on therapy or use of CGM. Other measures of chronic changes, when needed. (E) A1C (%) mg/dl mmol/l glycemia such as fructosamine are avail- 6 126 7.0 able, but their linkage to average glucoseBecause A1C is thought to reflect average 7 154 8.6 and their prognostic significance are notglycemia over several months (43) and 8 183 10.2 as clear as is the case for A1C.has strong predictive value for diabetes 9 212 11.8complications (11,46), A1C testing 10 240 13.4 2. Glycemic goals in adultsshould be performed routinely in all pa- ● Lowering A1C to below or around 7% 11 269 14.9tients with diabetes, at initial assessment 12 298 16.5 has been shown to reduce microvascu-and then as part of continuing care. Mea- These estimates are based on ADAG data of 2,700 lar and neuropathic complications ofsurement approximately every 3 months glucose measurements over 3 months per A1C mea- type 1 and type 2 diabetes. Therefore,determines whether a patient’s glycemic surement in 507 adults with type 1, type 2, and no for microvascular disease prevention,targets have been reached and main- diabetes. The correlation between A1C and average the A1C goal for nonpregnant adults intained. For any individual patient, the fre- glucose was 0.92 (49). A calculator for converting general is 7%. (A) A1C results into estimated average glucose (eAG),quency of A1C testing should be ● In type 1 and type 2 diabetes, random- in either mg/dl or mmol/l, is available atdependent on the clinical situation, the http://professional.diabetes.org/eAG. ized controlled trials of intensive versustreatment regimen used, and the judg- standard glycemic control have notment of the clinician. Some patients with shown a significant reduction in CVDstable glycemia well within target may do porting both an A1C result and an esti- outcomes during the randomized por-well with testing only twice per year, mated average glucose (eAG) result when tion of the trials. Long-term follow-upwhile unstable or highly intensively man- a clinician orders the A1C test. In previ- of the DCCT and UK Prospective Dia-aged patients (e.g., pregnant type 1 dia- ous versions of the Standards of Medical betes Study (UKPDS) cohorts suggestsbetic women) may be tested more Care in Diabetes, the table describing the that treatment to A1C targets below orfrequently than every 3 months. The correlation between A1C and mean glu- around 7% in the years soon after theavailability of the A1C result at the time cose was derived from relatively sparse diagnosis of diabetes is associated withthat the patient is seen (point-of-care test- data (one seven-point profile over 1 day long-term reduction in risk of macro-ing) has been reported to result in in- per A1C reading) in the primarily Cauca- vascular disease. Until more evidencecreased intensification of therapy and sian type 1 participants in the DCCT (50). becomes available, the general goal ofimprovement in glycemic control Clinicians should note that the numbers 7% appears reasonable for many(47,48). in the table are now different, as they are adults for macrovascular risk reduc- The A1C test is subject to certain lim- based on 2,800 readings per A1C in the tion. (B)itations. Conditions that affect erythro- ADAG trial. ● Subgroup analyses of clinical trials suchcyte turnover (hemolysis, blood loss) and In the ADAG trial, there were no sig- as the DCCT and UKPDS, and evidencehemoglobin variants must be considered, nificant differences among racial and eth- for reduced proteinuria in the Action inparticularly when the A1C result does not nic groups in the regression lines between Diabetes and Vascular Disease: Preteraxcorrelate with the patient’s clinical situa- A1C and mean glucose, although there and Diamicron Modified Release Con-tion (43). In addition, A1C does not pro- was a trend toward a difference between trolled Evaluation (ADVANCE) trialvide a measure of glycemic variability or Africans/African Americans participants suggest a small but incremental benefithypoglycemia. For patients prone to gly- and Caucasians that might have been sig- in microvascular outcomes with A1Ccemic variability (especially type 1 dia- nificant had more Africans/African Amer- values closer to normal. Therefore, forbetic patients, or type 2 diabetic patients icans been studied. A recent study selected individual patients, providerswith severe insulin deficiency), glycemic comparing A1C to CGM data in 48 type 1 might reasonably suggest even lowercontrol is best judged by the combination diabetic children found a highly statisti- A1C goals than the general goal ofof results of SMBG testing and the A1C. cally significant correlation between A1C 7%, if this can be achieved withoutThe A1C may also serve as a check on the and mean blood glucose, although the significant hypoglycemia or other ad-accuracy of the patient’s meter (or the pa- correlation (r 0.7) was significantly verse effects of treatment. Such patientstient’s reported SMBG results) and the ad- lower than in the ADAG trial (51). might include those with short dura-equacy of the SMBG testing schedule. Whether there are significant differences tion of diabetes, long life expectancy, Table 9 contains the correlation be- in how A1C relates to average glucose in and no significant CVD. (B)tween A1C levels and mean PG levels children or in African American patients ● Conversely, less-stringent A1C goalsbased on data from the international A1C- is an area for further study. For the time than the general goal of 7% may beDerived Average Glucose (ADAG) trial being, the question has not led to different appropriate for patients with a historyusing frequent SMBG and CGM in 507 recommendations about testing A1C or of severe hypoglycemia, limited life ex-adults (83% Caucasian) with type 1, type different interpretations of the clinical pectancy, advanced microvascular or2, and no diabetes (49). ADA and the meaning of given levels of A1C in those macrovascular complications, and ex-American Association of Clinical Chem- populations. tensive comorbid conditions and thoseists have determined that the correlation For patients in whom A1C/eAG and with longstanding diabetes in whom(r 0.92) is strong enough to justify re- measured blood glucose appear discrep- the general goal is difficult to attain de-care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S19
    • Standards of Medical Care spite diabetes self-management educa- analyses also suggest that further lowering such as stroke. In an epidemiologic anal- tion, appropriate glucose monitoring, of A1C from 7 to 6% is associated with ysis of the study cohort, a continuous as- and effective doses of multiple glucose- further reduction in the risk of microvas- sociation was observed such that for every lowering agents including insulin. (C) cular complications, albeit the absolute percentage point lower median on-study risk reductions become much smaller. A1C (e.g., 8 –7%), there was a statisticallyGlycemic control is fundamental to the The ADVANCE study of intensive versus significant 18% reduction in CVD events,management of diabetes. The DCCT, a standard glycemic control in type 2 dia- again with no glycemic threshold. A re-prospective, randomized, controlled trial betes found a statistically significant re- cent report of 10 years of follow-up of theof intensive versus standard glycemic duction in albuminuria with an A1C UKPDS cohort described, for the partici-control in patients with relatively recently target of 6.5% (achieved median A1C pants originally randomized to intensivediagnosed type 1 diabetes, showed defin- 6.3%) compared with standard therapy glycemic control compared with thoseitively that improved glycemic control is achieving a median A1C of 7.0% (63). randomized to conventional glycemicassociated with significantly decreased Given the substantially increased risk of control, long-term reductions in MI (15%rates of microvascular (retinopathy and hypoglycemia (particularly in those with with sulfonylurea or insulin as initialnephropathy) as well as neuropathic type 1 diabetes, but also in the recent type pharmacotherapy, 33% with metformincomplications (53). Follow-up of the 2 diabetes trials described below), the as initial pharmacotherapy, both statisti-DCCT cohorts in the Epidemiology of Di- concerning mortality findings in the Ac- cally significant) and in all-cause mortal-abetes Interventions and Complications tion to Control Cardiovascular Risk in Di- ity (13 and 27%, respectively, both(EDIC) study has shown persistence of abetes (ACCORD) trial described below statistically significant) (59).this effect in previously intensively and the relatively much greater effort re- Because of ongoing uncertainty re-treated subjects, even though their glyce- quired to achieve near-normoglycemia, garding whether intensive glycemic con-mic control has been equivalent to that of the risks of lower targets may outweigh trol can reduce the increased risk of CVDprevious standard arm subjects during the potential benefits on microvascular events in people with type 2 diabetes, sev-follow-up (54,55). complications on a population level. eral large long-term trials were launched In type 2 diabetes, the Kumamoto However, selected individual patients, es- in the past decade to compare the effectsstudy (56) and the UKPDS (57,58) dem- pecially those with little comorbidity and of intensive versus standard glycemiconstrated significant reductions in micro- long life expectancy (who may reap the control on CVD outcomes in relativelyvascular and neuropathic complications benefits of further lowering glycemia be- high-risk participants with establishedwith intensive therapy. Similar to the low 7%) may, at patient and provider type 2 diabetes. In 2008, results of threeDCCT-EDIC findings, long-term fol- judgment, adopt glycemic targets as close large trials (ACCORD, ADVANCE, andlow-up of the UKPDS cohort has recently to normal as possible as long as significant VADT) suggested no significant reductiondemonstrated a “legacy effect” of early in- hypoglycemia does not become a barrier. in CVD outcomes with intensive glycemictensive glycemic control on long-term Whereas many epidemiologic studies control in these populations. Details ofrates of microvascular complications, and meta-analyses (64,65) have clearly these three studies are shown in Table 10,even with loss of glycemic separation be- shown a direct relationship between A1C and their results and implications are re-tween the intensive and standard cohorts and CVD, the potential of intensive glyce- viewed more extensively in a recent ADAafter the end of the randomized con- mic control to reduce CVD has been less position statement (52).trolled trial (59). The more recent Veter- clearly defined. In the DCCT, there was a The ACCORD study randomizedans Affairs Diabetes Trial (VADT) in type trend toward lower risk of CVD events 10,251 participants with either history of2 diabetes also showed significant reduc- with intensive control (risk reduction a CVD event or significant CVD risk to ations in albuminuria with intensive 41%, 95% CI 10 – 68%), but the number strategy of intensive glycemic control (tar-(achieved median A1C 6.9%) compared of events was small. However, 9-year get A1C 6.0%) or standard glycemicwith standard glycemic control but no post-DCCT follow-up of the cohort has control (A1C target 7.0 –7.9%). Investiga-difference in retinopathy and neuropathy shown that participants previously ran- tors used multiple glycemic medications(60,61). domized to the intensive arm had a 42% in both arms. From a baseline median In each of these large randomized reduction (P 0.02) in CVD outcomes A1C of 8.1%, the intensive arm reached aprospective clinical trials, treatment regi- and a 57% reduction (P 0.02) in the median A1C of 6.4% within 12 months ofmens that reduced average A1C to 7% risk of nonfatal myocardial infarction randomization, while the standard group(1% above the upper limits of normal) (MI), stroke, or CVD death compared reached a median A1C of 7.5%. Otherwere associated with fewer markers of with participants previously in the stan- risk factors were treated aggressively andlong-term microvascular complications; dard arm (66). The benefit of intensive equally in both groups. The intensive gly-however, intensive control was found to glycemic control in this type 1 diabetic cemic control group had more use of in-increase the risk of severe hypoglycemia cohort has recently been shown to persist sulin in combination with multiple oraland led to weight gain (46,60,62). for up to 30 years (67). agents, significantly more weight gain, Epidemiological analyses of the The UKPDS trial of type 2 diabetes and more episodes of severe hypoglyce-DCCT and UKPDS (46,53) demonstrate a observed a 16% reduction in cardiovascu- mia than the standard group.curvilinear relationship between A1C and lar complications (combined fatal or non- In early 2008, the glycemic controlmicrovascular complications. Such anal- fatal MI and sudden death) in the arm of ACCORD was halted on the rec-yses suggest that, on a population level, intensive glycemic control arm, although ommendation of the study’s data safetythe greatest number of complications will this difference was not statistically signif- monitoring board due to the finding of anbe averted by taking patients from very icant (P 0.052), and there was no sug- increased rate of mortality in the intensivepoor control to fair or good control. These gestion of benefit on other CVD outcomes arm compared with the standard armS20 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementTable 10—Comparison of the three trials of intensive glycemic control and CVD outcomes ACCORD ADVANCE VADTParticipant characteristics n 10,251 11,140 1,791 Mean age (years) 62 66 60 Duration of diabetes (years) 10 8 11.5 History of CVD (%) 35 32 40 Median baseline A1C (%) 8.1 7.2 9.4 On insulin at baseline (%) 35 1.5 52Protocol characteristics A1C goals (%) (I vs. S)* 6.0 vs. 7.0–7.9 6.5 vs. “based on local guidelines” 6.0 (action if 6.5) vs. planned separation of 1.5 Protocol for glycemic control (I vs. S)* Multiple drugs in both Multiple drugs added to gliclizide vs. Multiple drugs in both arms arms multiple drugs with no gliclizide Management of other risk factors Embedded blood pressure Embedded blood pressure trial Protocol for intensive and lipid trials treatment in both armsOn-study characteristics Achieved median A1C (%) (I vs. S) 6.4 vs. 7.5 6.3 vs. 7.0 6.9 vs. 8.5 On insulin at study end (%) (I vs. S)* 77 vs. 55* 40 vs. 24 89 vs. 0.74Weight changes (kg) Intensive glycemic control arm 3.5 0.1 7.8 Standard glycemic control arm 0.4 1.0 3.4 Severe hypoglycemia (participants with one or more episodes during study) (%) Intensive glycemic control arm 16.2 2.7 21.2 Standard glycemic control arm 5.1 1.5 9.9Outcomes Definition of primary outcome Nonfatal MI, nonfatal Microvascular plus macrovascular Nonfatal MI, nonfatal stroke, stroke, CVD death (nonfatal MI, nonfatal stroke, CVD CVD death, death) outcomes hospitalization for heart failure, revascularization HR for primary outcome (95% CI) 0.90 (0.78–1.04) 0.9 (0.82–0.98); 0.88 (0.74–1.05) macrovascular 0.94 (0.84–1.06) HR for mortality findings (95% CI) 1.22 (1.01–1.46) 0.93 (0.83–1.06) 1.07 (0.81–1.42)*Insulin rates for ACCORD are for any use during the study. I, intensive glycemic control; S, standard glycemic control. Abridged from ref. 52.(1.41 vs. 1.14%/year, hazard ratio 1.22, The cause of excess deaths in the in- achieved A1C levels 7% or in those who95% CI 1.01–1.46), with a similar in- tensive group of the ACCORD has been lowered their A1C quickly after trial en-crease in cardiovascular deaths. The pri- difficult to pinpoint (and is discussed in rollment. In fact, the converse was ob-mary outcome of ACCORD (MI, stroke, some detail in a 2009 ADA position state- served: those at highest risk for mortalityor cardiovascular death) was lower in the ment [52]). However, exploratory analy- were participants in the intensive armintensive glycemic control group due to a ses of the mortality findings of ACCORD with the highest A1C levels.reduction in nonfatal MI, although this (evaluating variables including weight The ADVANCE study randomizedfinding was not statistically significant gain, use of any specific drug or drug participants to a strategy of intensive gly-when the study was terminated (68). Of combination, and hypoglycemia) were re- cemic control (with primary therapy be-note, prespecified subset analyses showed portedly unable to identify a clear expla- ing the sulfonylurea gliclizide andthat participants with no previous CVD nation for the excess mortality in the additional medications as needed toevent and those who had a baseline A1C intensive arm. At the 69th Scientific Ses- achieve a target A1C of 6.5%) or to stan- 8% had a statistically significant reduc- sions of the American Diabetes Associa- dard therapy (in which any medicationtion in the primary CVD outcome, al- tion, the ACCORD investigators but gliclizide could be used and the gly-though overall mortality was not reduced presented additional analyses showing no cemic target was according to “localin these groups. increase in mortality in participants who guidelines”). ADVANCE participantscare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S21
    • Standards of Medical Carewere slightly older than those in AC- exploratory analyses suggested that se- A prespecified subgroup analysis sug-CORD and VADT and had similar high vere hypoglycemia within the past 90 gested that major CVD outcome reduc-CVD risk. However, they had an average days was a strong predictor of the primary tion occurred in patients without knownduration of diabetes that was 2 years outcome and of CVD mortality (69). CVD at baseline (HR 0.84 [95% CI 0.74 –shorter, lower baseline A1C (median All three of these trials were carried 0.94]) (71). Conversely, the mortality7.2%), and almost no use of insulin at out in participants with established diabe- findings in ACCORD and subgroup anal-enrollment. The median A1C levels tes (mean duration 8 –11 years) and either yses of VADT suggest that the potentialachieved in the intensive and standard known CVD or multiple risk factors sug- risks of very intensive glycemic controlarms were 6.3 and 7.0%, respectively, gesting the presence of established ath- may outweigh its benefits in some pa-and maximal separation between the erosclerosis. Subset analyses of the three tients, such as those with very long dura-arms took several years to achieve. Use of trials suggested a significant benefit of in- tion of diabetes, known history of severeother drugs that favorably impact CVD tensive glycemic control on CVD in par- hypoglycemia, advanced atherosclerosis,risk (aspirin, statins, and angiotensin en- ticipants with shorter duration of and advanced age/frailty. Certainly, pro-zyme inhibitors) was lower in ADVANCE diabetes, lower A1C at entry, and/or ab- viders should be vigilant in preventing se-than in ACCORD or VADT. sence of known CVD. The DCCT-EDIC vere hypoglycemia in patients with The primary outcome of ADVANCE study and the long-term follow-up of the advanced disease and should not aggres-was a combination of microvascular UKPDS cohort both suggest that intensive sively attempt to achieve near-normalevents (nephropathy and retinopathy) glycemic control initiated soon after diag- A1C levels in patients in whom such aand major adverse cardiovascular events nosis of diabetes in patients with a lower target cannot be reasonably easily and(MI, stroke, and cardiovascular death). level of CVD risk may impart long-term safely achieved.Intensive glycemic control significantly protection from CVD events. As is the Recommended glycemic goals forreduced the primary end point, although case with microvascular complications, it nonpregnant adults are shown in Tablethis was due to a significant reduction in may be that glycemic control plays a 11. The recommendations are based onthe microvascular outcome, primarily de- greater role before macrovascular disease those for A1C values, with listed bloodvelopment of macroalbuminuria, with no is well developed and minimal or no role glucose levels that appear to correlatesignificant reduction in the macrovascu- when it is advanced. Consistent with this with achievement of an A1C of 7%. Thelar outcome. There was no difference in concept, data from an ancillary study of issue of pre- versus postprandial SMBGoverall or cardiovascular mortality be- VADT demonstrated that intensive glyce- targets is complex (72). Elevated post-tween the intensive compared with the mic control was quite effective in reduc- challenge (2-h OGTT) glucose valuesstandard glycemic control arms (63). ing CVD events in individuals with less have been associated with increased car- VADT randomized participants with atherosclerosis at baseline (assessed by diovascular risk independent of FPG intype 2 diabetes uncontrolled on insulin or coronary calcium) but not in people with some epidemiological studies. In diabeticmaximal dose oral agents (median entry more extensive baseline atherosclerosis subjects, some surrogate measures of vas-A1C 9.4%) to a strategy of intensive gly- (70). cular pathology, such as endothelial dys-cemic control (goal A1C 6.0%) or stan- The benefits of intensive glycemic function, are negatively affected bydard glycemic control, with a planned control on microvascular and neuro- postprandial hyperglycemia (73). It isA1C separation of at least 1.5%. Medica- pathic complications are well established clear that postprandial hyperglycemia,tion treatment algorithms were used to for both type 1 and type 2 diabetes. AD- like preprandial hyperglycemia, contrib-achieve the specified glycemic goals, with VANCE and VADT have added to that ev- utes to elevated A1C levels, with its rela-a goal of using similar medications in both idence base by demonstrating a tive contribution being higher at A1Cgroups. Median A1C levels of 6.9 and significant reduction in the risk of new or levels that are closer to 7%. However, out-8.4% were achieved in the intensive and worsening albuminuria with intensive come studies have clearly shown A1C tostandard arms, respectively, within the glycemic control. The lack of significant be the primary predictor of complica-1st year of the study. Other CVD risk fac- reduction in CVD events with intensive tions, and landmark glycemic control tri-tors were treated aggressively and equally glycemic control in ACCORD, AD- als such as the DCCT and UKPDS reliedin both groups. VANCE, and VADT should not lead clini- overwhelmingly on preprandial SMBG. The primary outcome of VADT was a cians to abandon the general target of an Additionally, a randomized controlledcomposite of CVD events. The cumulative A1C 7.0% and thereby discount the trial in patients with known CVD foundprimary outcome was nonsignificantly benefit of good control on serious and de- no CVD benefit of insulin regimens tar-lower in the intensive arm. There were bilitating microvascular complications. geting postprandial glucose comparedmore CVD deaths in the intensive arm The evidence for a cardiovascular with those targeting preprandial glucosethan in the standard arm, but the differ- benefit of intensive glycemic control pri- (74). For individuals who have premealence was not statistically significant (60). marily rests on long-term follow-up of glucose values within target but A1C val-Post hoc subgroup analyses suggested study cohorts treated early in the course ues above target, a reasonable recommen-that duration of diabetes interacted with of type 1 and type 2 diabetes as well as dation for postprandial testing and targetsrandomization such that participants subset analyses of ACCORD, ADVANCE, is monitoring postprandial plasma glu-with duration of diabetes less than about and VADT. A recent group-level meta- cose (PPG) 1–2 h after the start of the meal12 years appeared to have a CVD benefit analysis of the three trials suggests that and treatment aimed at reducing PPG val-of intensive glycemic control while those glucose lowering has a modest (9%) but ues to 180 mg/dl to help lower A1C.with longer duration of disease prior to statistically significant reduction in major As noted above, less stringent treat-study entry had a neutral or even adverse CVD outcomes, primarily nonfatal MI, ment goals may be appropriate for adultseffect of intensive glycemic control. Other with no significant increase in mortality. with limited life expectancies or advancedS22 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementTable 11 —Summary of glycemic recommendations for non-pregnant adults with diabetes b. Therapy for type 2 diabetes. The ADAA1C 7.0%* and the European Association for thePreprandial capillary plasma glucose 70–130 mg/dl (3.9–7.2 mmol/l) Study of Diabetes (EASD) published aPeak postprandial capillary plasma glucose† 180 mg/dl ( 10.0 mmol/l) consensus statement on the approach toKey concepts in setting glycemic goals: management of hyperglycemia in individ- ● A1C is the primary target for glycemic control uals with type 2 diabetes (80) and a sub- ● Goals should be individualized based on: sequent update (81). Highlights of this ● duration of diabetes approach include: intervention at the ● age/life expectancy time of diagnosis with metformin in com- ● comorbid conditions bination with lifestyle changes (MNT and ● known CVD or advanced microvascular exercise) and continuing timely augmen- complications tation of therapy with additional agents ● hypoglycemia unawareness (including early initiation of insulin ther- ● individual patient considerations apy) as a means of achieving and main- ● More or less stringent glycemic goals may be taining recommended levels of glycemic appropriate for individual patients control (i.e., A1C 7% for most patients).Postprandial glucose may be targeted if A1C goals are not The overall objective is to achieve and met despite reaching preprandial glucose goals maintain glycemic control and to change interventions when therapeutic goals are*Referenced to a nondiabetic range of 4.0 – 6.0% using a DCCT-based assay. †Postprandial glucose mea-surements should be made 1–2 h after the beginning of the meal, generally peak levels in patients with not being met.diabetes. The algorithm took into account the evidence for A1C lowering of the individ- ual interventions, their additive effects,vascular disease. Glycemic goals for chil- ous insulin infusion [CSII] or insulin and their expense. The precise drugs useddren are provided in VII.A.1.a. Glycemic pump therapy) was a key part of im- and their exact sequence may not be ascontrol. Severe or frequent hypoglycemia proved glycemia and better outcomes important as achieving and maintainingis an absolute indication for the modifica- (53,66). At the time of the study, therapy glycemic targets safely. Medications nottion of treatment regimens, including set- was carried out with short- and interme- included in the consensus algorithm, ow-ting higher glycemic goals. diate-acting human insulins. Despite bet- ing to less glucose-lowering effectiveness, Regarding goals for glycemic control ter microvascular outcomes, intensive limited clinical data, and/or relative ex-for women with GDM, recommendations insulin therapy was associated with a high pense, still may be appropriate choices forfrom the Fifth International Workshop- rate in severe hypoglycemia (62 episodes individual patients to achieve glycemicConference on Gestational Diabetes (75) per 100 patient-years of therapy). Since goals. Initiation of insulin at the time ofare to target maternal capillary glucose the time of the DCCT, a number of rapid- diagnosis is recommended for individualsconcentrations of: acting and long-acting insulin analogs presenting with weight loss or other se- have been developed. These analogs are vere hyperglycemic symptoms or signs.● Preprandial 95 mg/dl (5.3 mmol/l) associated with less hypoglycemia with and either equal A1C lowering in type 1 diabetes ● 1-h postmeal 140 mg/dl (7.8 (77,78). D. Medical nutrition therapy mmol/l) Recommended therapy for type 1 di- General recommendations or abetes therefore consists of the following ● Individuals who have pre-diabetes or ● 2-h postmeal 120 mg/dl (6.7 components: 1) use of multiple dose in- diabetes should receive individualized mmol/l) sulin injections (3– 4 injections per day of MNT as needed to achieve treatment basal and prandial insulin) or CSII ther- goals, preferably provided by a regis-For women with preexisting type 1 or apy; 2) matching of prandial insulin to tered dietitian familiar with the compo-type 2 diabetes who become pregnant, a carbohydrate intake, premeal blood glu- nents of diabetes MNT. (A)recent consensus statement (76) recom- cose, and anticipated activity; and 3) for ● Because it can result in cost savings andmends the following as optimal glycemic many patients (especially if hypoglycemia improved outcomes (B), MNT shouldgoals, if they can be achieved without ex- is a problem), use of insulin analogs. be covered by insurance and other pay-cessive hypoglycemia: There are excellent reviews available that ors (E). guide the initiation and management of● premeal, bedtime, and overnight glu- insulin therapy to achieve desired glyce- Energy balance, overweight, and cose 60 –99 mg/dl (3.3–5.4 mmol/l) mic goals (3,77,79).● peak postprandial glucose 100 –129 obesity Because of the increased frequency of ● In overweight and obese insulin- mg/dl (5.4 –7.1 mmol/l) other autoimmune diseases in type 1 dia-● A1C 6.0% resistant individuals, modest weight betes, screening for thyroid dysfunction, loss has been shown to reduce insulin vitamin B12 deficiency, or celiac disease resistance. Thus, weight loss is recom-3. Approach to treatment should be considered based on signs and mended for all overweight or obese in-a. Therapy for type 1 diabetes. The symptoms. Periodic screening in the ab- dividuals who have or are at risk forDCCT clearly showed that intensive insu- sence of symptoms has been recom- diabetes. (A)lin therapy (three or more injections per mended, but the effectiveness and ● For weight loss, either low-carbohy-day of insulin or continuous subcutane- optimal frequency are unclear. drate or low-fat calorie-restricted dietscare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S23
    • Standards of Medical Care may be effective in the short-term (up ● If adults with diabetes choose to use Because of the effects of obesity on to 1 year). (A) alcohol, daily intake should be limited insulin resistance, weight loss is an im-● For patients on low-carbohydrate diets, to a moderate amount (one drink per portant therapeutic objective for over- monitor lipid profiles, renal function, day or less for adult women and two weight or obese individuals with pre- and protein intake (in those with ne- drinks per day or less for adult men). diabetes or diabetes (94). Short-term phropathy) and adjust hypoglycemic (E) studies have demonstrated that moderate therapy as needed. (E) ● Routine supplementation with antioxi- weight loss (5% of body weight) in sub-● Physical activity and behavior modifi- dants, such as vitamins E and C and jects with type 2 diabetes is associated cation are important components of carotene, is not advised because of lack with decreased insulin resistance, im- weight loss programs and are most of evidence of efficacy and concern re- proved measures of glycemia and lipemia, helpful in maintenance of weight loss. lated to long-term safety. (A) and reduced blood pressure (95); longer- (B) ● Benefit from chromium supplementa- term studies ( 52 weeks) showed mixed tion in people with diabetes or obesity effects on A1C in adults with type 2 dia-Primary prevention of diabetes has not been conclusively demon- betes (96 –99), and results were con-● Among individuals at high risk for de- strated and therefore cannot be recom- founded by pharmacologic weight loss veloping type 2 diabetes, structured mended. (C) therapy. A systematic review of 80 weight programs emphasizing lifestyle ● Individualized meal planning should loss studies of 1 year duration demon- changes that include moderate weight include optimization of food choices to strated that moderate weight loss loss (7% body weight) and regular meet recommended dietary allowances achieved through diet alone, diet and ex- physical activity (150 min/week) with (RDAs)/dietary reference intakes ercise, and meal replacements can be dietary strategies including reduced (DRIs) for all micronutrients. (E) achieved and maintained over the long calories and reduced intake of dietary term (4.8 – 8% weight loss at 12 months fat can reduce the risk for developing MNT is an integral component of diabetes [100]). The multifactorial intensive life- diabetes and are therefore recom- prevention, management, and self- style intervention used in the DPP, which mended. (A) management education. In addition to its included reduced intake of fat and calo-● Individuals at high risk for type 2 dia- role in preventing and controlling diabe- ries, led to weight loss averaging 7% at 6 betes should be encouraged to achieve tes, ADA recognizes the importance of months and maintenance of 5% weight the U.S. Department of Agriculture nutrition as an essential component of an loss at 3 years, associated with a 58% re- (USDA) recommendation for dietary fi- overall healthy lifestyle. A full review of duction in incidence of type 2 diabetes ber (14 g fiber/1,000 kcal) and foods the evidence regarding nutrition in pre- (11). Look AHEAD (Action for Health in containing whole grains (one-half of venting and controlling diabetes and its Diabetes) is a large clinical trial designed grain intake). (B) complications and additional nutrition- to determine whether long-term weight related recommendations can be found in loss will improve glycemia and preventDietary fat intake in diabetes the ADA position statement, Nutrition cardiovascular events in subjects withmanagement Recommendations and Interventions for type 2 diabetes. One-year results of the● Saturated fat intake should be 7% of Diabetes, published in 2006 and updated intensive lifestyle intervention in this trial total calories. (A) for 2008 (82). Achieving nutrition- show an average of 8.6% weight loss, sig-● Reducing intake of trans fat lowers LDL related goals requires a coordinated team nificant reduction of A1C, and reduction cholesterol and increases HDL choles- effort that includes the active involvement in several CVD risk factors (101). When terol (A); therefore intake of trans fat of the person with pre-diabetes or diabe- completed, the Look AHEAD study should be minimized (E). tes. Because of the complexity of nutrition should provide insight into the effects of issues, it is recommended that a registered long-term weight loss on important clin-Carbohydrate intake in diabetes dietitian who is knowledgeable and ical outcomes.management skilled in implementing nutrition therapy The optimal macronutrient distribu-● Monitoring carbohydrate intake, into diabetes management and education tion of weight loss diets has not been es- whether by carbohydrate counting, ex- be the team member who provides MNT. tablished. Although low-fat diets have changes, or experience-based estima- Clinical trials/outcome studies of traditionally been promoted for weight tion, remains a key strategy in achieving MNT have reported decreases in A1C at loss, several randomized controlled trials glycemic control. (A) 3– 6 months ranging from 0.25 to 2.9% found that subjects on low-carbohydrate● For individuals with diabetes, use of the with higher reductions seen in type 2 di- diets ( 130 g/day of carbohydrate) lost glycemic index and glycemic load may abetes of shorter duration. Multiple stud- more weight at 6 months than subjects on provide a modest additional benefit for ies have demonstrated sustained low-fat diets (102,103); however, at 1 glycemic control over that observed improvements in A1C at 12 months and year, the difference in weight loss be- when total carbohydrate is considered longer when a registered dietitian pro- tween the low-carbohydrate and low-fat alone. (B) vided follow-up visits ranging from diets was not significant and weight loss monthly to three sessions per year (83– was modest with both diets. AnotherOther nutrition recommendations 90). Meta-analyses of studies in nondia- study of overweight women randomized●Sugar alcohols and nonnutritive sweet- betic, free-living subjects report that MNT to one of four diets showed significantly eners are safe when consumed within reduces LDL cholesterol by 15–25 mg/dl more weight loss at 12 months with the the acceptable daily intake levels estab- (91) or by up to 16% (92), while clinical Atkins low-carbohydrate diet than with lished by the Food and Drug Adminis- trials support a role for lifestyle modifica- higher-carbohydrate diets (104). tration (FDA). (A) tion in treating hypertension (92,93). Changes in serum triglyceride and HDLS24 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementcholesterol were more favorable with the acids on people with diabetes; therefore, passing or transposing sections of thelow-carbohydrate diets. In one study, the recommended goals are consistent small intestine, when part of a compre-those subjects with type 2 diabetes dem- with those for individuals with CVD hensive team approach, can be an effec-onstrated a greater decrease in A1C with a (92,109). tive weight loss treatment for severelow-carbohydrate diet than with a low-fat The FDA has approved five nonnutri- obesity, and national guidelines supportdiet (103). A recent meta-analysis showed tive sweeteners for use in the U.S.: acesul- its consideration for people with type 2that at 6 months, low-carbohydrate diets fame potassium, aspartame, neotame, diabetes who have BMI 35 kg/m2. Bari-were associated with greater improve- saccharin, and sucralose. Before being al- atric surgery has been shown to lead toments in triglyceride and HDL cholesterol lowed on the market, all underwent rig- near or complete normalization of glyce-concentrations than low-fat diets; how- orous scrutiny and were shown to be safe mia in 55–95% of patients with type 2ever, LDL cholesterol was significantly when consumed by the public, including diabetes, depending on the surgical pro-higher with the low-carbohydrate diets people with diabetes and women during cedure. A meta-analysis of studies of bari-(105). In a 2-year dietary intervention pregnancy. Reduced calorie sweeteners atric surgery reported that 78% ofstudy, Mediterranean and low-carbohy- approved by the FDA include sugar alco- individuals with type 2 diabetes had com-drate diets were found to be effective and hols (polyols) such as erythritol, isomalt, plete “resolution” of diabetes (normaliza-safe alternatives to a low-fat diet for lactitol, maltitol, mannitol, sorbitol, xyli- tion of blood glucose levels in the absenceweight reduction in moderately obese tol, tagatose, and hydrogenated starch hy- of medications) and that the resolutionparticipants (99). drolysates. The use of sugar alcohols rates were sustained in studies that had The RDA for digestible carbohydrate appears to be safe; however, they may follow-up exceeding 2 years (110). Reso-is 130 g/day and is based on providing cause diarrhea, especially in children. Ste- lution rates are lower with proceduresadequate glucose as the required fuel for via (Rebaudioside A) has been designated that only constrict the stomach andthe central nervous system without reli- by the FDA as being generally recognized higher with those that bypass portions ofance on glucose production from ingested as safe (GRAS). the small intestine. Additionally, there is aprotein or fat. Although brain fuel needs suggestion that intestinal bypass proce-can be met on lower-carbohydrate diets, Reimbursement for MNT dures may have glycemic effects that arelong-term metabolic effects of very-low- MNT, when delivered by a registered dieti- independent of their effects on weight.carbohydrate diets are unclear, and such tian according to nutrition practice guide- A recent randomized controlled trialdiets eliminate many foods that are im- lines, is reimbursed as part of the Medicare compared adjustable gastric banding toportant sources of energy, fiber, vitamins, program as overseen by the Centers for the “best available” medical and lifestyleand minerals that are important in dietary Medicare and Medicaid Services (www. therapy in subjects with type 2 diabetespalatability (106). cms.hhs.gov/ medicalnutritiontherapy). diagnosed 2 years before randomiza- Although numerous studies have at- tion and with BMI 30 – 40 kg/m2 (111). Intempted to identify the optimal mix of E. Bariatric surgery this trial, 73% of surgically treated pa-macronutrients for meal plans of people tients achieved “remission” of their diabe-with diabetes, it is unlikely that one such Recommendations tes, compared with 13% of those treatedcombination of macronutrients exists. ● Bariatric surgery should be considered medically. The latter group lost only 1.7%The best mix of carbohydrate, protein, for adults with BMI 35 kg/m2 and of body weight, suggesting that their ther-and fat appears to vary depending on type 2 diabetes, especially if the diabe- apy was not optimal. Overall the trial hadindividual circumstances. For those tes or associated comorbidities are dif- 60 subjects, and only 13 had a BMI 35individuals seeking guidance as to macro- ficult to control with lifestyle and kg/m2, making it difficult to generalizenutrient distribution in healthy adults, pharmacologic therapy. (B) these results to diabetic patients who areDRIs may be helpful (106). It must be ● Patients with type 2 diabetes who have less severely obese or with longer dura-clearly recognized that regardless of the undergone bariatric surgery need life- tion of diabetes.macronutrient mix, the total caloric in- long lifestyle support and medical moni- Bariatric surgery is costly in the shorttake must be appropriate to the weight toring. (E) term and has some risks. Rates of morbiditymanagement goal. Further, individualiza- ● Although small trials have shown glyce- and mortality directly related to the surgerytion of the macronutrient composition mic benefit of bariatric surgery in patients have been reduced considerably in recentwill depend on the metabolic status of the with type 2 diabetes and BMI of 30 –35 years, with 30-day mortality rates nowpatient (e.g., lipid profile and renal func- kg/m2, there is currently insufficient evi- 0.28%, similar to those of laparoscopic cho-tion) and/or food preferences. Plant- dence to generally recommend surgery in lecystectomy (112). Longer-term concernsbased diets (vegan or vegetarian) that are patients with BMI 35 kg/m2 outside of a include vitamin and mineral deficiencies,well planned and nutritionally adequate research protocol. (E) osteoporosis, and rare but often severe hy-have also been shown to improve meta- ● The long-term benefits, cost-effectiveness, poglycemia from insulin hypersecretion.bolic control (107,108). and risks of bariatric surgery in individ- Cohort studies attempting to match sub- The primary goal with respect to di- uals with type 2 diabetes should be jects suggest that the procedure may reduceetary fat in individuals with diabetes is to studied in well-designed, randomized longer-term mortality rates (113), and it islimit saturated fatty acids, trans fatty ac- controlled trials with optimal medical reasonable to postulate that there may beids, and cholesterol intake so as to reduce and lifestyle therapy as the comparator. recouping of costs over the long term. How-risk for CVD. Saturated and trans fatty ac- (E) ever, studies of the mechanisms of glycemicids are the principal dietary determinants improvement, long-term benefits and risks,of plasma LDL cholesterol. There is a lack Gastric reduction surgery, either gastric and cost-effectiveness of bariatric surgery inof evidence on the effects of specific fatty banding or procedures that involve by- individuals with type 2 diabetes will requirecare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S25
    • Standards of Medical Carewell-designed, randomized clinical trials diabetes make informed self-management overseen by the Centers for Medicare andwith optimal medical and lifestyle therapy decisions. Care of diabetes has shifted to Medicaid Services (www.cms.hhs.gov/of diabetes and cardiovascular risk factors as an approach that is more patient centered DiabetesSelfManagement).the comparators. and places the person with diabetes at the center of the care model working in col- G. Physical activityF. Diabetes self-management laboration with health care professionals.education Patient-centered care is respectful of and Recommendations responsive to individual patient prefer- ● People with diabetes should be advisedRecommendations ences, needs, and values and ensures that to perform at least 150 min/week of● People with diabetes should receive patient values guide all decision making moderate-intensity aerobic physical ac- DSME according to national standards (123). tivity (50 –70% of maximum heart when their diabetes is diagnosed and as rate). (A) needed thereafter. (B) 1. Evidence for the benefits of DSME ● In the absence of contraindications,● Effective self-management and quality Multiple studies have found that DSME is people with type 2 diabetes should be of life are the key outcomes of DSME associated with improved diabetes encouraged to perform resistance train- and should be measured and moni- knowledge and self-care behavior (115); ing three times per week. (A) tored as part of care. (C) improved clinical outcomes such as lower● DSME should address psychosocial is- A1C (116,117,119,120,124), lower self- ADA technical reviews on exercise in pa- sues, since emotional well-being is as- reported weight (115), improved quality tients with diabetes, currently being up- sociated with positive diabetes of life (118,125), and healthy coping dated, have summarized the value of outcomes. (C) (126); and lower costs (127). Better out- exercise in the diabetes management plan● Because DSME can result in cost- comes were reported for DSME interven- (143,144). Regular exercise has been savings and improved outcomes (B), tions that were longer and included shown to improve blood glucose control, DSME should be reimbursed by third- follow-up support (115,128 –131), that reduce cardiovascular risk factors, con- party payors. (E) were culturally (132) and age appropriate tribute to weight loss, and improve well (133,134) and tailored to individual being. Furthermore, regular exercise may DSME is an essential element of dia- needs and preferences (114), and that ad- prevent type 2 diabetes in high-risk indi-betes care (114 –120), and national stan- dressed psychosocial issues (114,115, viduals (11–13). Structured exercise in-dards for DSME (121) are based on 119,135). Both individual and group ap- terventions of at least 8 weeks’ durationevidence for its benefits. Education helps proaches have been found effective (136 – have been shown to lower A1C by an av-people with diabetes initiate effective self- 138). There is growing evidence for the erage of 0.66% in people with type 2 di-management and cope with diabetes role of community health workers and abetes, even with no significant change inwhen they are first diagnosed. Ongoing peer (139) and lay leaders (140) in deliv- BMI (145). Higher levels of exercise in-DSME and support also help people with ering DSME and support in addition to tensity are associated with greater im-diabetes maintain effective self- the core team (141). provements in A1C and fitness (146).management throughout a lifetime of di- Diabetes education is associated withabetes as they face new challenges and as increased use of primary and preventive 1. Frequency and type of exercisetreatment advances become available. services and lower use of acute, inpatient The U.S. Department of Health and Hu-DSME helps patients optimize metabolic hospital services (127). Patients who par- man Services’ Physical Activity Guide-control, prevent and manage complica- ticipate in diabetes education are more lines for Americans (147) suggest thattions, and maximize quality of life in a likely to follow best practice treatment adults over age 18 years perform 150 min/cost-effective manner (122). recommendations, particularly among week of moderate-intensity or 75 min/ DSME is the on-going process of fa- the medicare population, and to have week of vigorous aerobic physical activitycilitating the knowledge, skill, and ability lower Medicare and commercial claim or an equivalent combination of the two.necessary for diabetes self-care (121). costs (142). In addition, the guidelines suggest thatThis process incorporates the needs, adults also do muscle-strengthening ac-goals, and life experiences of the person 2. National Standards for DSME tivities that involve all major musclewith diabetes. The overall objectives of The National Standards for DSME are de- groups two or more days per week. TheDSME are to support informed decision- signed to define quality diabetes self- guidelines suggest that adults over age 65making, self-care behaviors, problem- management education and to assist years, or those with disabilities, follow thesolving, and active collaboration with the diabetes educators in a variety of settings adult guidelines if possible or (if this is nothealth care team and to improve clinical to provide evidence-based education possible) be as physically active as theyoutcomes, health status, and quality of life (121). The standards, most recently re- are able. Studies included in the meta-in a cost-effective manner (121). vised in 2007, are reviewed and updated analysis of effects of exercise interventions Current best practice of DSME is a every 5 years by a task force representing on glycemic control (145) had a meanskills-based approach that focuses on key organizations involved in the field of number of sessions per week of 3.4, withhelping those with diabetes make in- diabetes education and care. a mean of 49 min/session. The DPP life-formed self-management choices. DSME style intervention, which included 150has changed from a didactic approach fo- 3. Reimbursement for DSME min/week of moderate intensity exercise,cusing on providing information, to a DSME, when provided by a program that had a beneficial effect on glycemia inmore theoretically based empowerment meets ADA recognition standards, is re- those with pre-diabetes. Therefore, itmodel that focuses on helping those with imbursed as part of the Medicare program seems reasonable to recommend that peo-S26 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementple with diabetes try to follow the physical sumption is not altered. For individuals H. Psychosocial assessment and careactivity guidelines for the general on these therapies, added carbohydratepopulation. should be ingested if pre-exercise glucose Recommendations Progressive resistance exercise im- levels are 100 mg/dl (5.6 mmol/l) ● Assessment of psychological and socialproves insulin sensitivity in older men (154,155). Hypoglycemia is rare in dia- situation should be included as an on-with type 2 diabetes to the same or even to betic individuals who are not treated with going part of the medical managementa greater extent as aerobic exercise (148). insulin or insulin secretagogues, and no of diabetes. (E)Clinical trials have provided strong evi- preventive measures for hypoglycemia ● Psychosocial screening and follow-updence for the A1C-lowering value of re- are usually advised in these cases. should include, but is not limited to,sistance training in older adults with type attitudes about the illness, expectations2 diabetes (149,150) and for an additive for medical management and out-benefit of combined aerobic and resis- 4. Exercise in the presence of specific comes, affect/mood, general and diabe-tance exercise in adults with type 2 diabe- long-term complications of diabetes tes-related quality of life, resourcestes (151). a. Retinopathy. In the presence of pro- (financial, social, and emotional), and liferative diabetic retinopathy (PDR) or psychiatric history. (E)2. Evaluation of the diabetic patient severe non-proliferative diabetic retinop- ● Screen for psychosocial problems suchbefore recommending an exercise athy (NPDR), vigorous aerobic or resis- as depression and diabetes-related dis-program tance exercise may be contraindicated tress, anxiety, eating disorders, andPrior guidelines have suggested that be- because of the risk of triggering vitreous cognitive impairment when self-fore recommending a program of physical hemorrhage or retinal detachment (156). management is poor. (C)activity, the provider should assess pa- b. Peripheral neuropathy. Decreasedtients with multiple cardiovascular risk pain sensation in the extremities results in Psychological and social problems canfactors for coronary artery disease (CAD). increased risk of skin breakdown and in- impair the ability of the individual (162–As further discussed in VI.A.5. Coronary fection and of Charcot joint destruction. 164) or the family to carry out diabetesheart disease screening and treatment, the Prior recommendations have advised care tasks and therefore compromisearea of screening asymptomatic diabetic non–weight-bearing exercise for patients health status. There are opportunities forpatients for CAD remains unclear, and a with severe peripheral neuropathy. Stud- the clinician to assess psychosocial statusrecent ADA consensus statement on this ies have shown that moderate-intensity in a timely and efficient manner so thatissue concluded that routine screening is walking may not lead to increased risk of referral for appropriate services can benot recommended (152). Providers foot ulcers or reulceration in those with accomplished.should use clinical judgment in this area. peripheral neuropathy (157). All individ- Key opportunities for screening ofCertainly, high-risk patients should be uals with peripheral neuropathy should psychosocial status occur at diagnosis,encouraged to start with short periods of wear proper footwear and examine their during regularly scheduled managementlow-intensity exercise and to increase the feet daily for early detection of lesions. visits, during hospitalizations, at discov-intensity and duration slowly. Anyone with a foot injury or open sore ery of complications, or when problems Providers should assess patients for should be restricted to non–weight- with glucose control, quality of life, or ad-conditions that might contraindicate cer- bearing activities. herence are identified. Patients are likelytain types of exercise or predispose to in- c. Autonomic neuropathy. Autonomic to exhibit psychological vulnerability atjury, such as uncontrolled hypertension, neuropathy can increase the risk of exer- diagnosis and when their medical statussevere autonomic neuropathy, severe pe- cise-induced injury or adverse events changes, i.e., the end of the honeymoonripheral neuropathy or history of foot le- through decreased cardiac responsive- period, when the need for intensifiedsions, and unstable proliferative ness to exercise, postural hypotension, treatment is evident, and when complica-retinopathy. The patient’s age and previ- impaired thermoregulation, impaired tions are discovered (164).ous physical activity level should be night vision due to impaired papillary re- Issues known to impact self-considered. action, and unpredictable carbohydrate management and health outcomes in- delivery from gastroparesis predisposing clude but are not limited to: attitudes3. Exercise in the presence of to hypoglycemia (158). Autonomic neu- about the illness, expectations for medicalnonoptimal glycemic control ropathy is also strongly associated with management and outcomes, affect/mood,a. Hyperglycemia. When people with CVD in people with diabetes (159,160). general and diabetes-related quality oftype 1 diabetes are deprived of insulin for People with diabetic autonomic neuropa- life, diabetes-related distress (165), re-12– 48 h and are ketotic, exercise can thy should undergo cardiac investigation sources (financial, social, and emotional)worsen hyperglycemia and ketosis (153); before beginning physical activity more (166), and psychiatric history (167,168).therefore, vigorous activity should be intense than that to which they are Screening tools are available for a numberavoided in the presence of ketosis. How- accustomed. of these areas (135). Indications for refer-ever, it is not necessary to postpone exer- d. Albuminuria and nephropathy. Phys- ral to a mental health specialist familiarcise simply based on hyperglycemia, ical activity can acutely increase urinary with diabetes management may includeprovided the patient feels well and urine protein excretion. However, there is no gross noncompliance with medical regi-and/or blood ketones are negative. evidence that vigorous exercise increases men (by self or others) (168), depressionb. Hypoglycemia. In individuals taking the rate of progression of diabetic kidney with the possibility of self-harminsulin and/or insulin secretagogues, disease and likely no need for any specific (169,170), debilitating anxiety (alone orphysical activity can cause hypoglycemia exercise restrictions for people with dia- with depression), indications of an eatingif medication dose or carbohydrate con- betic kidney disease (161). disorder, or cognitive functioning thatcare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S27
    • Standards of Medical Caresignificantly impairs judgment. It is pref- sured. Infection or dehydration are more Severe hypoglycemia (where the indi-erable to incorporate psychological as- likely to necessitate hospitalization of the vidual requires the assistance of anothersessment and treatment into routine care person with diabetes than the person person and cannot be treated with oralrather than waiting for identification of a without diabetes. carbohydrate due to confusion or uncon-specific problem or deterioration in psy- The hospitalized patient should be sciousness) should be treated using emer-chological status (135). Although the cli- treated by a physician with expertise in gency glucagon kits, which require anician may not feel qualified to treat the management of diabetes. For further prescription. Those in close contact withpsychological problems, using the pa- information on management of patients or who have custodial care of people withtient-provider relationship as a founda- with hyperglycemia in the hospital, see hypoglycemia-prone diabetes (familytion for further treatment can increase the VIII.A. Diabetes care in the hospital. For members, roommates, school personnel,likelihood that the patient will accept re- further information on management of child care providers, correctional institu-ferral for other services. It is important to DKA or nonketotic hyperosmolar state, tion staff, or coworkers) should be in-establish that emotional well-being is part refer to the ADA consensus statement on structed in use of such kits. An individualof diabetes management. hyperglycemic crises (173). does not need to be a health care profes- sional to safely administer glucagon. CareI. When treatment goals are not met K. Hypoglycemia should be taken to ensure that unexpiredFor a variety of reasons, some people with glucagon kits are available.diabetes and their health care providers Recommendations Prevention of hypoglycemia is a crit-do not achieve the desired goals of treat- ● Glucose (15–20 g) is the preferred ical component of diabetes management.ment (Table 11). Rethinking the treat- treatment for the conscious individual Teaching people with diabetes to balancement regimen may require assessment of with hypoglycemia, although any form insulin use, carbohydrate intake, and ex-barriers including income, health literacy, of carbohydrate that contains glucose ercise is a necessary but not always suffi-diabetes distress, depression, and com- may be used. If SMBG 15 min after cient strategy. In type 1 diabetes andpeting demands, including those related treatment shows continued hypoglyce- severely insulin-deficient type 2 diabetes,to family responsibilities and dynamics. mia, the treatment should be repeated. the syndrome of hypoglycemia unaware-Other strategies may include culturally Once SMBG glucose returns to normal, ness, or hypoglycemia-associated auto-appropriate and enhanced DSME, co- the individual should consume a meal nomic failure, can severely compromisemanagement with a diabetes team, refer- or snack to prevent recurrence of hypo- stringent diabetes control and quality ofral to a medical social worker for glycemia. (E) life. The deficient counter-regulatory hor-assistance with insurance coverage, or ● Glucagon should be prescribed for all mone release and autonomic responses inchange in pharmacological therapy. Initi- individuals at significant risk of severe this syndrome are both risk factors foration of or increase in SMBG, utilization hypoglycemia, and caregivers or family and are caused by hypoglycemia. A corol-of CGM, frequent contact with the pa- members of these individuals should be lary to this “vicious cycle” is that severaltient, or referral to a mental health profes- instructed in its administration. Gluca- weeks of avoidance of hypoglycemia hassional or physician with special expertise gon administration is not limited to been demonstrated to improve counter-in diabetes may be useful. Providing pa- health care professionals. (E) regulation and awareness to some extenttients with an algorithm for self-titration ● Individuals with hypoglycemia un- in many patients (174,176,177). Hence,of insulin doses based on SMBG results awareness or one or more episodes of patients with one or more episodes of se-may be helpful for type 2 patients who severe hypoglycemia should be advised vere hypoglycemia may benefit from attake insulin (171). to raise their glycemic targets to strictly least short-term relaxation of glycemic avoid further hypoglycemia for at least targets.J. Intercurrent illness several weeks to partially reverse hypo-The stress of illness, trauma, and/or sur- glycemia unawareness and reduce riskgery frequently aggravates glycemic con- of future episodes. (B) L. Immunizationtrol and may precipitate diabeticketoacidosis (DKA) or nonketotic hyper- Hypoglycemia is the leading limiting fac-osmolar state, life-threatening conditions tor in the glycemic management of type 1 Recommendationsthat require immediate medical care to and insulin-treated type 2 diabetes (174). ● Annually provide an influenza vaccineprevent complications and death (172). Treatment of hypoglycemia (PG 70 mg/ to all diabetic patients 6 months ofAny condition leading to deterioration in dl) requires ingestion of glucose- or car- age. (C)glycemic control necessitates more fre- bohydrate-containing foods. The acute ● Administer pneumococcal polysaccha-quent monitoring of blood glucose and glycemic response correlates better with ride vaccine to all diabetic patients 2(in ketosis-prone patients) urine or blood the glucose content than with the carbo- years of age. A one-time revaccination isketones. Marked hyperglycemia requires hydrate content of the food. Although recommended for individuals 64temporary adjustment of the treatment pure glucose is the preferred treatment, years of age previously immunizedprogram and, if accompanied by ketosis, any form of carbohydrate that contains when they were 65 years of age if thevomiting, or alteration in level of con- glucose will raise blood glucose. Added vaccine was administered 5 yearssciousness, immediate interaction with fat may retard and then prolong the acute ago. Other indications for repeat vacci-the diabetes care team. The patient treated glycemic response (175). Ongoing activ- nation include nephrotic syndrome,with noninsulin therapies or MNT alone ity of insulin or insulin secretagogues may chronic renal disease, and other immu-may temporarily require insulin. Ade- lead to recurrence of hypoglycemia unless nocompromised states, such as afterquate fluid and caloric intake must be as- further food is ingested after recovery. transplantation. (C)S28 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementInfluenza and pneumonia are common, such a strategy may be desirable to under- m2 and a loop diuretic for those with anpreventable infectious diseases associated take in adult patients prior to instituting estimated GFR 30 ml min/1.73 m2.with high mortality and morbidity in the preventive therapy. (C)elderly and in people with chronic dis- ● Multiple drug therapy (two or moreeases. Though there are limited studies 1. Hypertension/blood pressure agents at maximal doses) is generallyreporting the morbidity and mortality of control required to achieve blood pressure tar-influenza and pneumococcal pneumonia gets. (B)specifically in people with diabetes, ob- Recommendations ● If ACE inhibitors, ARBs, or diuretics areservational studies of patients with a vari- used, kidney function and serum potas-ety of chronic illnesses, including Screening and diagnosis sium levels should be closely moni- ● Blood pressure should be measured atdiabetes, show that these conditions are tored. (E)associated with an increase in hospitaliza- every routine diabetes visit. Patients ● In pregnant patients with diabetes andtions for influenza and its complications. found to have systolic blood pressure chronic hypertension, blood pressurePeople with diabetes may be at increased 130 mmHg or diastolic blood pres- target goals of 110 –129/65–79 mmHgrisk of the bacteremic form of pneumo- sure 80 mmHg should have blood are suggested in the interest of long-coccal infection and have been reported pressure confirmed on a separate day. term maternal health and minimizingto have a high risk of nosocomial bactere- Repeat systolic blood pressure 130 impaired fetal growth. ACE inhibitorsmia, which has a mortality rate as high as mmHg or diastolic blood pressure 80 and ARBs are contraindicated during50% (178). mmHg confirms a diagnosis of hyper- pregnancy. (E) Safe and effective vaccines are avail- tension. (C)able that can greatly reduce the risk ofserious complications from these diseases Goals Hypertension is a common comorbidity(179,180). In a case-control series, influ- ● Patients with diabetes should be treated of diabetes that affects the majority of pa-enza vaccine was shown to reduce diabe- to a systolic blood pressure 130 tients, with prevalence depending on typetes-related hospital admission by as much mmHg. (C) of diabetes, age, obesity, and ethnicity.as 79% during flu epidemics (179). There ● Patients with diabetes should be treated Hypertension is a major risk factor foris sufficient evidence to support that peo- to a diastolic blood pressure 80 both CVD and microvascular complica-ple with diabetes have appropriate sero- mmHg. (B) tions. In type 1 diabetes, hypertension islogic and clinical responses to these often the result of underlying nephropa-vaccinations. The Centers for Disease Treatment thy, while in type 2 diabetes it usuallyControl and Prevention’s Advisory Com- ● Patients with a systolic blood pressure coexists with other cardiometabolic riskmittee on Immunization Practices recom- 130 –139 mmHg or a diastolic blood factors.mends influenza and pneumococcal pressure 80 – 89 mmHg may be given a. Screening and diagnosis. Measure-vaccines for all individuals with diabetes lifestyle therapy alone for a maximum ment of blood pressure in the office(http://www.cdc.gov/vaccines/recs/). For of 3 months, and then if targets are not should be done by a trained individuala complete discussion on the prevention achieved, patients should be treated and should follow the guidelines estab-of influenza and pneumococcal disease in with the addition of pharmacological lished for nondiabetic individuals: mea-people with diabetes, consult the techni- agents. (E) surement in the seated position, with feetcal review and position statement on this ● Patients with more severe hypertension on the floor and arm supported at heartsubject (178,181). (systolic blood pressure 140 mmHg level, after 5 min of rest. Cuff size should or diastolic blood pressure 90 be appropriate for the upper arm circum-VI. PREVENTION AND mmHg) at diagnosis or follow-up ference. Elevated values should be con-MANAGEMENT OF should receive pharmacologic therapy firmed on a separate day. Because of theDIABETES COMPLICATIONS in addition to lifestyle therapy. (A) clear synergistic risks of hypertension and ● Lifestyle therapy for hypertension con- diabetes, the diagnostic cutoff for a diag-A. Cardiovascular disease sists of weight loss if overweight, nosis of hypertension is lower in peopleCVD is the major cause of morbidity and DASH-style dietary pattern including with diabetes (blood pressure 130/80mortality for individuals with diabetes and reducing sodium and increasing potas- mmHg) than in those without diabetesthe largest contributor to the direct and in- sium intake, moderation of alcohol in- (blood pressure 140/90 mmHg) (184).direct costs of diabetes. The common con- take, and increased physical activity. Home blood pressure self-monitoringditions coexisting with type 2 diabetes (e.g., (B) and 24-h ambulatory blood pressurehypertension and dyslipidemia) are clear ● Pharmacologic therapy for patients monitoring may provide additional evi-risk factors for CVD, and diabetes itself con- with diabetes and hypertension should dence of “white coat” and masked hyper-fers independent risk. Numerous studies be paired with a regimen that includes tension and other discrepancies betweenhave shown the efficacy of controlling indi- either an ACE inhibitor or an angioten- office and “true” blood pressure, andvidual cardiovascular risk factors in pre- sin II receptor blocker (ARB). If one studies in nondiabetic populations showventing or slowing CVD in people with class is not tolerated, the other should that home measurements may correlatediabetes. Large benefits are seen when mul- be substituted. If needed to achieve better with CVD risk than office measure-tiple risk factors are addressed globally blood pressure targets, a thiazide di- ments (185,186). However, the prepon-(182,183). Risk for coronary heart disease uretic should be added to those with an derance of the clear evidence of benefits ofand CVD in general can be estimated using estimated glomerular filtration rate treatment of hypertension in people withmultivariable risk factor approaches, and (GFR) (see below) 30 ml min/1.73 diabetes is based on office measurements.care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S29
    • Standards of Medical Careb. Treatment goals. Randomized clinical reducing cardiovascular events (194 – optimal doses of at least three antihyper-trials have demonstrated the benefit (re- 196). However, a variety of other studies tensive agents of different classifications,duction of coronary heart disease [CHD] have shown no specific advantage to ACE one of which should be a diuretic, clini-events, stroke, and nephropathy) of low- inhibitors as initial treatment of hyperten- cians should consider an evaluation forering blood pressure to 140 mmHg sys- sion in the general hypertensive popula- secondary forms of hypertension.tolic and 80 mmHg diastolic in tion, but rather an advantage on During pregnancy in diabetic womenindividuals with diabetes (184,187–189). cardiovascular outcomes of initial therapy with chronic hypertension, target bloodEpidemiologic analyses show that blood with low-dose thiazide diuretics pressure goals of 110 –129 mmHg sys-pressure 115/75 mmHg is associated (184,197,198). tolic and 65–79 mmHg diastolic are rea-with increased cardiovascular event rates In people with diabetes, inhibitors of sonable, as they contribute to long-termand mortality in individuals with diabetes the renin-angiotensin system (RAS) may maternal health. Lower blood pressure(184,190,191). Therefore, a target blood have unique advantages for initial or early levels may be associated with impairedpressure goal of 130/80 mmHg is rea- therapy of hypertension. In a nonhyper- fetal growth. During pregnancy, treat-sonable if it can be achieved safely. The tension trial of high-risk individuals in- ment with ACE inhibitors and ARBs isongoing ACCORD trial is designed to de- cluding a large subset with diabetes, an contraindicated, since they can cause fetaltermine whether blood pressure lowering ACE inhibitor reduced CVD outcomes damage. Antihypertensive drugs knownto systolic blood pressure 120 mmHg (199). In patients with congestive heart to be effective and safe in pregnancy in-provides greater cardiovascular protec- failure (CHF), including diabetic sub- clude methyldopa, labetalol, diltiazem,tion than a systolic blood pressure level of groups, ARBs have been shown to reduce clonidine, and prazosin. Chronic diuretic 140 mmHg in patients with type 2 dia- major CVD outcomes (200 –203), and in use during pregnancy has been associatedbetes (192). type 2 patients with significant nephrop- with restricted maternal plasma volume,c. Treatment strategies. Although there athy, ARBs were superior to calcium which might reduce uteroplacental perfu-are no well-controlled studies of diet and channel blockers for reducing heart fail- sion (209).exercise in the treatment of hypertension ure (204 –206). Though evidence for dis-in individuals with diabetes, the Dietary tinct advantages of RAS inhibitors on 2. Dyslipidemia/lipid managementApproaches to Stop Hypertension CVD outcomes in diabetes remains con-(DASH) study in nondiabetic individuals flicting (187,207), the high CVD risks as- Recommendationshas shown antihypertensive effects simi- sociated with diabetes, and the highlar to those of pharmacologic mono- prevalence of undiagnosed CVD, may still Screeningtherapy. Lifestyle therapy consists of favor recommendations for their use as ● In most adult patients, measure fastingreducing sodium intake (to 1,500 mg/ first-line hypertension therapy in people lipid profile at least annually. In adultsday) and excess body weight; increasing with diabetes (184). Recently, the blood with low-risk lipid values (LDL choles-consumption of fruits, vegetables (8 –10 pressure arm of the ADVANCE trial dem- terol 100 mg/dl, HDL cholesterolservings/day), and low-fat dairy products onstrated that routine administration of a 50 mg/dl, and triglycerides 150(2–3 servings/day); avoiding excessive al- fixed combination of the ACE inhibitor mg/dl), lipid assessments may be re-cohol consumption (no more than two perindopril and the diuretic indapamide peated every 2 years. (E)servings per day in men and no more than significantly reduced combined micro-one serving per day in women); and in- vascular and macrovascular outcomes, as Treatment recommendations and goalscreasing activity levels (184,193). These well as CVD and total mortality. The im- ● Lifestyle modification focusing on thenonpharmacological strategies may also proved outcomes also could have been reduction of saturated fat, trans fat,positively affect glycemia and lipid con- due to lower achieved blood pressure in and cholesterol intake; increase of n-3trol. Their effects on cardiovascular the perindopril-indapamide arm (208). fatty acids, viscous fiber, and plantevents have not been established. An ini- In addition, the ACCOMPLISH (Avoiding stanols/sterols; weight loss (if indi-tial trial of nonpharmacologic therapy Cardiovascular Events in Combination cated); and increased physical activitymay be reasonable in diabetic individu- Therapy in Patients Living with Systolic should be recommended to improveals with mild hypertension (systolic Hypertension) trial showed a decrease in the lipid profile in patients with dia-130 –139 mmHg or diastolic 80 – 89 morbidity and mortality in those receiv- betes. (A)mmHg). If the blood pressure is 140 ing benazapril and amlodipine versus ● Statin therapy should be added to life-mmHg systolic and/or 90 mmHg dia- benazapril and hydrochlorothiazide. The style therapy, regardless of baselinestolic at the time of diagnosis, pharma- compelling benefits of RAS inhibitors in lipid levels, for diabetic patients:cologic therapy should be initiated diabetic patients with albuminuria or re- ● with overt CVD. (A)along with nonpharmacologic therapy nal insufficiency provide additional ratio- ● without CVD who are over the age of(184). nale for use of these agents (see below, 40 years and have one or more other Lowering of blood pressure with reg- VI.B. Nephropathy screening and CVD risk factors. (A)imens based on a variety of antihyperten- treatment). ● For patients at lower risk than de-sive drugs, including ACE inhibitors, An important caveat is that most pa- scribed above (e.g., without overt CVDARBs, -blockers, diuretics, and calcium tients with hypertension require multi- and under the age of 40 years), statinchannel blockers, has been shown to be drug therapy to reach treatment goals, therapy should be considered in addi-effective in reducing cardiovascular especially diabetic patients whose targets tion to lifestyle therapy if LDL choles-events. Several studies suggested that are lower. Many patients will require terol remains 100 mg/dl or in thoseACE inhibitors may be superior to dihy- three or more drugs to reach target goals with multiple CVD risk factors. (E)dropyridine calcium channel blockers in (184). If blood pressure is refractory to ● In individuals without overt CVD, theS30 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position StatementTable 12—Reduction in 10-year risk of major CVD endpoints (CHD death/non-fatal MI) in major statin trials, or sub-studies of major trials,in diabetic subjects (N 16,032) LDL CVD Relative risk Absolute risk cholesterolStudy (ref.) prevention Statin dose and comparator Risk reduction reduction reduction reduction (%)4S-DM (211) 2° Simvastatin 20–40 mg vs. placebo 85.7 to 43.2% 50% 42.5% 186 to 119 mg/dl (36%)ASPEN 2° (216) 2° Atorvastatin 10 mg vs. placebo 39.5 to 24.5% 34% 12.7% 112 to 79 mg/dl (29%)HPS-DM (212) 2° Simvastatin 40 mg vs. placebo 43.8 to 36.3% 17% 7.5% 123 to 84 mg/dl (31%)CARE-DM (213) 2° Pravastatin 40 mg vs. placebo 40.8 to 35.4% 13% 5.4% 136 to 99 mg/dl (27%)TNT-DM (214) 2° Atorvastatin 80 mg vs. 10 mg 26.3 to 21.6% 18% 4.7% 99 to 77 mg/dl (22%)HPS-DM (212) 1° Simvastatin 40 mg vs. placebo 17.5 to 11.5% 34% 6.0% 124 to 86 mg/dl (31%)CARDS (234) 1° Atorvastatin 10 mg vs. placebo 11.5 to 7.5% 35% 4.0% 118 to 71 mg/dl (40%)ASPEN 1° (216) 1° Atorvastatin 10 mg vs. placebo 9.8 to 7.9% 19% 1.9% 114 to 80 mg/dl (30%)ASCOT-DM (215) 1° Atorvastatin 10 mg vs. placebo 11.1 to 10.2% 8% 0.9% 125 to 82 mg/dl (34%)Studies were of differing lengths (3.3–5.4 years) and used somewhat different outcomes, but all reported rates of CVD death and non-fatal MI. In this tabulation,results of the statin on 10-year risk of major CVD endpoints (CHD death/non-fatal MI) are listed for comparison between studies. Correlation between 10-year CVDrisk of the control group and the absolute risk reduction with statin therapy is highly significant (P 0.0007). Analyses provided by Craig Williams, PharmD, OregonHealth & Science University, 2007. primary goal is an LDL cholesterol nificant primary and secondary abetic subgroup of a larger trial (219). 100 mg/dl (2.6 mmol/l). (A) prevention of CVD events with and with- However, in a large trial specific to dia-● In individuals with overt CVD, a lower out CHD deaths in diabetic populations. betic patients, fenofibrate failed to re- LDL cholesterol goal of 70 mg/dl (1.8 As shown in Table 12, and similar to find- duce overall cardiovascular outcomes mmol/l), using a high dose of a statin, is ings in nondiabetic subjects, reduction in (221). an option. (B) “hard” CVD outcomes (CHD death and b. Dyslipidemia treatment and target● If drug-treated patients do not reach the nonfatal MI) can be more clearly seen in lipid levels. For most patients with dia- above targets on maximal tolerated sta- diabetic subjects with high baseline CVD betes, the first priority of dyslipidemia tin therapy, a reduction in LDL choles- risk (known CVD and/or very high LDL therapy (unless severe hypertriglyceride- terol of 30 – 40% from baseline is an cholesterol levels), but overall the benefits mia is the immediate issue) is to lower alternative therapeutic goal. (A) of statin therapy in people with diabetes at LDL cholesterol to a target goal of 100● Triglycerides levels 150 mg/dl (1.7 moderate or high risk for CVD are mg/dl (2.60 mmol/l) (222). Lifestyle in- mmol/l) and HDL cholesterol 40 convincing. tervention, including MNT, increased mg/dl (1.0 mmol/l) in men and 50 Low levels of HDL cholesterol, often physical activity, weight loss, and smok- mg/dl (1.3 mmol/l) in women, are de- associated with elevated triglyceride lev- ing cessation, may allow some patients to sirable. However, LDL cholesterol– els, are the most prevalent pattern of dys- reach lipid goals. Nutrition intervention targeted statin therapy remains the lipidemia in people with type 2 diabetes. should be tailored according to each pa- preferred strategy. (C) However, the evidence base for drugs that tient’s age, type of diabetes, pharmacolog-● If targets are not reached on maximally target these lipid fractions is significantly ical treatment, lipid levels, and other tolerated doses of statins, combination less robust than that for statin therapy medical conditions and should focus on therapy using statins and other lipid- (217). Nicotinic acid has been shown to the reduction of saturated fat, cholesterol, lowering agents may be considered to reduce CVD outcomes (218), although and trans unsaturated fat intake and in- achieve lipid targets but has not been the study was done in a nondiabetic co- creases in n-3 fatty acids, viscous fiber evaluated in outcome studies for either hort. Gemfibrozil has been shown to de- (such as in oats, legumes, citrus), and CVD outcomes or safety. (E) crease rates of CVD events in subjects plant stanols/sterols. Glycemic control● Statin therapy is contraindicated in without diabetes (219,220) and in a di- can also beneficially modify plasma lipid pregnancy. (E) levels, particularly in patients with very high triglycerides and poor glycemica. Evidence for benefits of lipid-lowering Table 13—Summary of recommendations control.therapy. Patients with type 2 diabetes for glycemic, blood pressure, and lipid control In those with clinical CVD or who arehave an increased prevalence of lipid ab- for adults with diabetes over age 40 years and have CVD risk fac-normalities, contributing to their high tors, pharmacological treatment shouldrisk of CVD. Over the past decade or A1C 7.0%* be added to lifestyle therapy regardless of Blood pressure 130/80 mmHgmore, multiple clinical trials have demon- baseline lipid levels. Statins are the drugs Lipidsstrated significant effects of pharmaco- of choice for lowering LDL cholesterol. LDL cholesterol 100 mg/dl ( 2.6logic (primarily statin) therapy on CVD In patients other than those described mmol/l)†outcomes in subjects with CHD and for above, statin treatment should be consid-primary CVD prevention (210). Analyses *Referenced to a nondiabetic range of 4.0 – 6.0% ered if there is an inadequate LDL choles- using a DCCT-based assay. †In individuals withof diabetic subgroups of larger trials overt CVD, a lower LDL cholesterol goal of 70 terol response to lifestyle modifications(211–215) and trials specifically in sub- mg/dl (1.8 mmol/l), using a high dose of a statin, is and improved glucose control or if thejects with diabetes (216,217) showed sig- an option. patient has increased cardiovascular riskcare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S31
    • Standards of Medical Care(e.g., multiple cardiovascular risk factors brate, ezetimibe, and bile acid seques- for glycemic, blood pressure, and lipidor long duration of diabetes). Very little trants all offer additional LDL cholesterol control for adults with diabetes, see Tableclinical trial evidence exists for type 2 di- lowering. The evidence that combination 13.abetic patients under the age of 40 years therapy provides a significant incrementand for type 1 diabetic patients of any age. in CVD risk reduction over statin therapy 3. Antiplatelet agentsIn the Heart Protection Study (lower age alone is still elusive.limit 40 years), the subgroup of 600 pa- d. Treatment of other lipoprotein frac- Recommendationstients with type 1 diabetes had a propor- tions or targets. Severe hypertriglyceri- ● Consider aspirin therapy (75–162 mg/tionately similar reduction in risk as demia may warrant immediate therapy of day) as a primary prevention strategy inpatients with type 2 diabetes although not this abnormality with lifestyle and usually those with type 1 or type 2 diabetes atstatistically significant (212). Although pharmacologic therapy (fibric acid deriv- increased cardiovascular risk (10-yearthe data are not definitive, consideration ative or niacin) to reduce the risk of acute risk 10%). This includes most menshould be given to lipid-lowering goals pancreatitis. In the absence of severe hy- 50 years of age or women 60 yearsfor type 1 diabetic patients similar to pertriglyceridemia, therapy targeting of age who have at least one additionalthose for type 2 diabetic patients, partic- HDL cholesterol or triglycerides has intu- major risk factor (family history ofularly if other cardiovascular risk factors itive appeal but lacks the evidence base of CVD, hypertension, smoking, dyslipi-are present. statin therapy (186). If the HDL choles- demia, or albuminuria). (C)c. Alternative LDL cholesterol goals. terol is 40 mg/dl and the LDL choles- ● There is not sufficient evidence to rec-Virtually all trials of statins and CVD out- terol is 100 –129 mg/dl, gemfibrozil or ommend aspirin for primary preven-come have tested specific doses of statins niacin might be used, especially if a pa- tion in lower risk individuals, such asagainst placebo, other doses of statin, or tient is intolerant to statins. Niacin is the men 50 years of age or women 60other statins, rather than aiming for spe- most effective drug for raising HDL cho- years of age without other major riskcific LDL cholesterol goals (223). As can lesterol. It can significantly increase blood factors. For patients in these age-groupsbe seen in Table 10, placebo-controlled glucose at high doses, but recent studies with multiple other risk factors, clinicaltrials generally achieved LDL cholesterol demonstrate that at modest doses (750 – judgment is required. (C)reductions of 30 – 40% from baseline. 2,000 mg/day), significant improvements ● Use aspirin therapy (75–162 mg/day)Hence, LDL cholesterol lowering of this in LDL cholesterol, HDL cholesterol, and as a secondary prevention strategy inmagnitude is an acceptable outcome for triglyceride levels are accompanied by those with diabetes with a history ofpatients who cannot reach LDL choles- only modest changes in glucose that are CVD. (A)terol goals due to severe baseline eleva- generally amenable to adjustment of dia- ● For patients with CVD and docu-tions in LDL cholesterol and/or betes therapy (230,231). mented aspirin allergy, clopidogrel (75intolerance of maximal, or any, statin Combination therapy with a statin mg/day) should be used. (B)doses. Additionally, for those with base- and a fibrate or a statin and niacin may be ● Combination therapy with ASA (75–line LDL cholesterol minimally 100 mg/ efficacious for treatment of all three lipid 162 mg/day) and clopidogrel (75 mg/dl, prescribing statin therapy to lower fractions, but this combination is associ- day) is reasonable for up to a year afterLDL cholesterol to 30 – 40% from base- ated with an increased risk for abnormal an acute coronary syndrome. (B)line is probably more effective than pre- transaminase levels, myositis, or rhabdo-scribing just enough to get LDL myolysis. The risk of rhabdomyolysis is ADA and the American Heart Associationcholesterol slightly 100 mg/dl. higher with higher doses of statins and (AHA) have, in the past, jointly recom- Recent clinical trials in high-risk pa- with renal insufficiency and seems to be mended that low-dose aspirin therapy betients, such as those with acute coronary lower when statins are combined with fe- used as a primary prevention strategy insyndromes or previous cardiovascular nofibrate than gemfibrozil (232). Several those with diabetes at increased cardio-events (224 –226), have demonstrated ongoing trials may provide much-needed vascular risk, including those who arethat more aggressive therapy with high evidence for the effects of combination over 40 years of age or those with addi-doses of statins to achieve an LDL choles- therapy on cardiovascular outcomes. tional risk factors (family history of CVD,terol of 70 mg/dl led to a significant re- In 2008, a consensus panel convened hypertension, smoking, dyslipidemia, orduction in further events. Therefore, a by ADA and the American College of Car- albuminuria) (235). These recommenda-reduction in LDL cholesterol to a goal of diology (ACC) recommended a greater tions were derived from several older tri- 70 mg/dl is an option in very-high-risk focus on non-HDL cholesterol and apo als that included small numbers ofdiabetic patients with overt CVD (227). lipoprotein B (apo B) in patients who are patients with diabetes. In individual patients, LDL choles- likely to have small LDL particles, such as Aspirin has been shown to be effec-terol lowering with statins is highly vari- people with diabetes (233). The consen- tive in reducing cardiovascular morbidityable, and this variable response is poorly sus panel suggested that for statin-treated and mortality in high-risk patients withunderstood (228). Reduction of CVD patients in whom the LDL cholesterol previous MI or stroke (secondary preven-events with statins correlates very closely goal would be 70 mg/dl (non-HDL cho- tion). Its net benefit in primary preven-with LDL cholesterol lowering (229). lesterol 100 mg/dl), apo B should be tion among patients with no previousWhen maximally tolerated doses of st- measured and treated to 80 mg/dl. For cardiovascular events is more controver-atins fail to significantly lower LDL cho- patients on statins with an LDL choles- sial, both for patients with and withoutlesterol ( 30% reduction from patients terol goal of 100 mg/dl (non-HDL cho- a history of diabetes (236). The U.S.baseline), the primary aim of combination lesterol 130 mg/dl), apo B should be Preventive Services Task Force recentlytherapy should be to achieve additional measured and treated to 90 mg/dl. updated its evidence base and recommen-LDL cholesterol lowering. Niacin, fenofi- For a summary of recommendations dations about aspirin use for primary pre-S32 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementvention (237,238). The Task Force Based on the currently available evi- set by the incidence of significant bleed-recommended encouraging aspirin use in dence, aspirin appears to have a modest ing. Clinical judgment should be used formen 45–79 and women 55–79 years of effect on ischemic vascular events with those at intermediate risk (younger pa-age and not encouraging aspirin use in the absolute decrease in events depending tients with one or risk factors or older pa-younger adults and did not differentiate on the underlying CVD risk. The main tients with no risk factors; those with 10-based on the presence or absence of adverse effects appear to be an increased year CVD risk 5–10%) until furtherdiabetes. risk of gastrointestinal bleeding. The ex- research is available. Use of aspirin in pa- Two recent randomized controlled cess risk may be as high as 1–5 per 1,000 tients under the age of 21 years is contra-trials of aspirin specifically in patients per year in real-world settings. In adults indicated due to the associated risk ofwith diabetes failed to show a significant with CVD risk greater than 1% per year, Reye’s syndrome.reduction in CVD end points, raising fur- the number of CVD events prevented will Clopidogrel has been demonstratedther questions about the efficacy of aspi- be similar to or greater than the number of to reduce CVD events in diabetic individ-rin for primary prevention in people with episodes of bleeding induced, although uals (247). It is recommended as adjunc-diabetes (239,240). In 2009, ADA AHA, these complications do not have equal ef- tive therapy in the 1st year after an acuteand ACC convened a group of experts to fects on long-term health (241). coronary syndrome or as alternative ther-review and synthesize the available evi- Average daily dosages used in most apy in aspirin-intolerant patients.dence and use this information to create clinical trials involving patients with dia-an updated recommendation. Their re- betes ranged from 50 – 650 mg but were 4. Smoking cessationport, including analyses in addition to mostly in the range of 100 –325 mg/day.those described below, will be published There is little evidence to support any spe- Recommendationsin early 2010. cific dose, but using the lowest possible ● Advise all patients not to smoke. (A) The ATT (Anti-Thrombotic Trialists’) dosage may help reduce side effects ● Include smoking cessation counselingcollaborators recently published an indi- (242). Although platelets from patients and other forms of treatment as a rou-vidual patient-level meta-analysis of the with diabetes have altered function, it is tine component of diabetes care. (B)six large trials of aspirin for primary pre- unclear what, if any, impact that findingvention in the general population (236). has on the required dose of aspirin for Issues of smoking and diabetes are reviewedThese trials collectively enrolled over cardioprotective effects in the patient in detail in the ADA technical review (248) with diabetes. Many alternate pathways and position statement (249) on this topic.95,000 participants, including almost for platelet activation exist that are inde- A large body of evidence from epidemiolog-4,000 with diabetes. Overall, they found pendent of thromboxane A2 and thus not ical, case-control, and cohort studies pro-that aspirin reduced the risk of vascular sensitive to the effects of aspirin (243). vides convincing documentation of theevents by 12% (RR 0.88 [95% CI 0.82– Therefore, while “aspirin resistance” ap- causal link between cigarette smoking and0.94]). The largest reduction was for non- pears higher in diabetic patients when health risks. Cigarette smoking contributesfatal MI (0.77 [0.67– 0.89]). Aspirin had measured by a variety of ex vivo and in to one of every five deaths in the U.S. and islittle effect on CHD death (0.95 [0.78 – vitro methods (platelet aggrenometry,1.15]) or total stroke (0.95 [0.85–1.06]). the most important modifiable cause of pre- measurement of thromboxane B2), theseThe net effect on total stroke reflected a mature death. Much of the prior work doc- observations alone are insufficient to em-relative reduction in risk of ischemic umenting the impact of smoking on health pirically recommend at this time thatstroke ( 14%) and a relative increased did not separately discuss results on subsets higher doses of aspirin be used in the di-risk of hemorrhagic stroke ( 32%). of individuals with diabetes, suggesting that abetic patient (244 –246).There was some evidence of a difference the identified risks are at least equivalent to Aspirin use for secondary preventionin aspirin effect by sex. Aspirin reduced continues to have a strong evidence base those found in the general population.CHD events in men (0.77 [0.67– 0.89]) and is recommended. Until further evi- Other studies of individuals with diabetesbut not in women (0.95 [0.77–1.17]). dence is available, low-dose (75–162 mg/ consistently found a heightened risk ofConversely, aspirin had no effect on day) aspirin use for primary prevention is CVD and premature death among smokers.stroke in men (1.01 [0.74 –1.39]) but re- reasonable for adults with diabetes and no Smoking is also related to the premature de-duced stroke in women (0.77 [0.59 – previous history of vascular disease who velopment of microvascular complications0.99]). These potential differences in are at increased CVD risk (10-year risk of of diabetes and may have a role in the de-effect by sex were of borderline statistical CVD events 10%) and who are not at velopment of type 2 diabetes.significance, were affected strongly by the increased risk for bleeding. This generally A number of large randomized clini-results of one trial, and cannot be consid- includes most men over age 50 years and cal trials have demonstrated the efficacyered definitive. Notably, sex differences in women over age 60 years who also have and cost-effectiveness of smoking cessa-aspirin’s effects have not been observed in one or more of the following major risk tion counseling in changing smoking be-studies of secondary prevention (236). In factors: smoking, hypertension, dyslipi- havior and reducing tobacco use. Thethe six trials examined by the ATT collab- demia, family history of premature CVD, routine and thorough assessment of to-orators, the effect of aspirin on major vas- and albuminuria. bacco use is important as a means of pre-cular events was similar for patients with Aspirin should not be recommended venting smoking or encouragingand without diabetes (0.88 [0.67–1.15] for those at low CVD risk (women under cessation. Special considerations shouldand 0.87 [0.79 – 0.96], respectively). The age 60 years and men under age 50 years include assessment of level of nicotine de-CI was wider for those with diabetes be- with no major CVD risk factors; 10-year pendence, which is associated with diffi-cause of their smaller number. CVD risk 5%), as the low benefit is off- culty in quitting and relapse (250,251).care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S33
    • Standards of Medical Care5. Coronary heart disease screening dial perfusion imaging in more than one and ARBs, there is clinical trial supportand treatment in five patients, cardiac outcomes were es- for each of the following statements: sentially equal (and very low) in screened ● In patients with type 1 diabetes, hy-Recommendations versus unscreened patients. Accordingly, pertension, and any degree of albu- the overall effectiveness, especially the minuria, ACE inhibitors have beenScreening cost-effectiveness, of such an indiscrimi- shown to delay the progression of ne-● In asymptomatic patients, evaluate risk nate screening strategy is in question. phropathy. (A) factors to stratify patients by 10-year In all patients with diabetes, cardio- ● In patients with type 2 diabetes, hy- risk, and treat risk factors accordingly. vascular risk factors should be assessed at pertension, and microalbuminuria, (B) least annually. These risk factors include both ACE inhibitors and ARBs have dyslipidemia, hypertension, smoking, a been shown to delay the progressionTreatment positive family history of premature cor- to macroalbuminuria. (A)● In patients with known CVD, ACE in- onary disease, and the presence of micro- ● In patients with type 2 diabetes, hy- hibitor (C), aspirin (A), and statin ther- or macroalbuminuria. Abnormal risk pertension, macroalbuminuria, and apy (A) (if not contraindicated) should factors should be treated as described renal insufficiency (serum creatinine be used to reduce the risk of cardiovas- elsewhere in these guidelines. Patients at 1.5 mg/dl), ARBs have been shown cular events. increased CHD risk should receive aspirin to delay the progression of nephrop-● In patients with a prior MI, -blockers and a statin, and ACE inhibitor, or ARB athy. (A) should be continued for at least 2 years therapy if hypertensive, unless there are ● If one class is not tolerated, the other after the event. (B) contraindications to a particular drug should be substituted. (E)● Longer-term use of -blockers in the class. While clear benefit exists for ACE ● Reduction of protein intake to 0.8 –1.0 absence of hypertension is reasonable if inhibitor and ARB therapy in patients g kg body wt–1 day–1 in individuals well tolerated, but data are lacking. (E) with nephropathy or hypertension, the with diabetes and the earlier stages of● Avoid thiazolidinedione (TZD) treat- benefits in patients with CVD in the ab- CKD and to 0.8 g kg body wt–1 day–1 ment in patients with symptomatic sence of these conditions is less clear, in the later stages of CKD may improve heart failure. (C) especially when LDL cholesterol is con- measures of renal function (urine albu-● Metformin may be used in patients with comitantly controlled (257,258). min excretion rate and GFR) and is rec- stable CHF if renal function is normal. ommended. (B) It should be avoided in unstable or hos- B. Nephropathy screening and ● When ACE inhibitors, ARBs, or diuret- pitalized patients with CHF. (C) treatment ics are used, monitor serum creatinine and potassium levels for the develop-Screening for CAD is reviewed in a re- Recommendations ment of acute kidney disease and hy-cently updated consensus statement (93). perkalemia. (E)To identify the presence of CAD in dia- General recommendations ● Continued monitoring of urine albu- ● To reduce the risk or slow the progres-betic patients without clear or suggestive min excretion to assess both responsesymptoms, a risk factor– based approach sion of nephropathy, optimize glucose to therapy and progression of disease isto the initial diagnostic evaluation and control. (A) recommended. (E) ● To reduce the risk or slow the progres- ●subsequent follow-up has intuitive ap- Consider referral to a physician experi-peal. However, recent studies concluded sion of nephropathy, optimize blood enced in the care of kidney diseasethat using this approach fails to identify pressure control. (A) when there is uncertainty about the eti-which patients will have silent ischemia ology of kidney disease (active urineon screening tests (159,252). Screening sediment, absence of retinopathy, or Candidates for cardiac testing include ● Perform an annual test to assess urine rapid decline in GFR), difficult manage-those with 1) typical or atypical cardiac albumin excretion in type 1 diabetic pa- ment issues, or advanced kidney dis-symptoms and 2) an abnormal resting tients with diabetes duration of 5 years ease. (B)electrocardiogram (ECG). The screening and in all type 2 diabetic patients, start-of asymptomatic patients remains contro- ing at diagnosis. (E) Diabetic nephropathy occurs in 20 – 40%versial, especially since intensive medical ● Measure serum creatinine at least annu- of patients with diabetes and is the singletherapy, indicated in diabetic patients at ally in all adults with diabetes regard- leading cause of end-stage renal diseasehigh risk for CVD, has an increasing evi- less of the degree of urine albumin (ESRD). Persistent albuminuria in thedence base for providing equal outcomes excretion. The serum creatinine should range of 30 –299 mg/24 h (microalbu-to invasive revascularization, including in be used to estimate GFR and stage the minuria) has been shown to be the earliestdiabetic patients (253,254). There is also level of chronic kidney disease (CKD), stage of diabetic nephropathy in type 1recent preliminary evidence that silent if present. (E) diabetes and a marker for development ofmyocardial ischemia may reverse over nephropathy in type 2 diabetes. Mi-time, adding to the controversy concern- Treatment croalbuminuria is also a well-establisheding aggressive screening strategies (255). ● In the treatment of the nonpregnant pa- marker of increased CVD risk (259,260).Finally, a recent randomized observa- tient with micro- or macroalbuminuria, Patients with microalbuminuria whotional trial demonstrated no clinical ben- either ACE inhibitors or ARBs should progress to macroalbuminuria ( 300efit to routine screening of asymptomatic be used. (A) mg/24 h) are likely to progress to ESRDpatients with type 2 diabetes and normal ● While there are no adequate head-to- (261,262). However, a number of inter-ECGs (256). Despite abnormal myocar- head comparisons of ACE inhibitors ventions have been demonstrated to re-S34 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementduce the risk and slow the progression of Table 14—Definitions of abnormalities in al- cation (Table 15) is primarily based onrenal disease. bumin excretion GFR levels and therefore differs from Intensive diabetes management other systems, in which staging is basedwith the goal of achieving near- Spot collection primarily on urinary albumin excretionnormoglycemia has been shown in large ( g/mg (284). Studies have found decreased GFRprospective randomized studies to de- Category creatinine) in the absence of increased urine albuminlay the onset of microalbuminuria and excretion in a substantial percentage ofthe progression of micro- to macroalbu- Normal 30 adults with diabetes (285,286). Epidemi-minuria in patients with type 1 Microalbuminuria 30–299 ologic evidence suggests that a substantial(263,264) and type 2 (57,58) diabetes. Macroalbuminuria (clinical) 300 fraction of those with CKD in the settingThe UKPDS provided strong evidence of diabetes have little or no detectable al-that control of blood pressure can re- buminuria (285). Serum creatinineduce the development of nephropathy should be used as additional therapy to should therefore be measured at least an-(187). In addition, large prospective further lower blood pressure in patients nually in all adults with diabetes, regard-randomized studies in patients with already treated with ACE inhibitors or less of the degree of urine albumintype 1 diabetes have demonstrated that ARBs (204) or as alternate therapy in the excretion.achievement of lower levels of systolic rare individual unable to tolerate ACE in- Serum creatinine should be used toblood pressure ( 140 mmHg) resulting hibitors or ARBs. estimate GFR and to stage the level offrom treatment using ACE inhibitors Studies in patients with varying stages CKD, if present. Estimated GFR (eGFR) isprovides a selective benefit over other of nephropathy have shown that protein commonly co-reported by laboratories orantihypertensive drug classes in delay- restriction helps slow the progression of can be estimated using formulae such asing the progression from micro- to mac- albuminuria, GFR decline, and occur- the Modification of Diet in Renal Diseaseroalbuminuria and can slow the decline rence of ESRD (278 –281). Protein re- (MDRD) study equation (287). Recent re-in GFR in patients with macroalbumin- striction should be considered ports have indicated that the MDRD isuria (205,206,265). In type 2 diabetes particularly in patients whose nephropa- more accurate for the diagnosis and strat-with hypertension and normoalbuminuria, thy seems to be progressing despite opti- ification of CKD in patients with diabetesRAS inhibition has been demonstrated to mal glucose and blood pressure control than the Cockcroft-Gault formula (288).delay onset of microalbuminuria (266). and use of ACE inhibitor and/or ARBs GFR calculators are available at http:// In addition, ACE inhibitors have been (281). www.nkdep.nih.gov.shown to reduce major CVD outcomes The role of continued annual quanti-(i.e., MI, stroke, and death) in patients Assessment of albuminuria status tative assessment of albumin excretion af-with diabetes (199), thus further support- and renal function ter diagnosis of microalbuminuria anding the use of these agents in patients with Screening for microalbuminuria can be institution of ACE inhibitor or ARB ther-microalbuminuria, a CVD risk factor. performed by measurement of the albu- apy and blood pressure control is unclear.ARBs do not prevent microalbuminuria in min-to-creatinine ratio in a random spot Continued surveillance can assess bothnormotensive patients with type 1 or type collection (preferred method); 24-h or response to therapy and progression of2 diabetes (267,268); however, ARBs timed collections are more burdensome disease. Some suggest that reducing ab-have been shown to reduce the rate of and add little to prediction or accuracy normal albuminuria ( 30 mg/g) to theprogression from micro- to macroalbu- (282,283). Measurement of a spot urine normal or near-normal range may im-minuria as well as ESRD in patients with for albumin only, whether by immunoas- prove renal and cardiovascular prognosis,type 2 diabetes (269 –271). Some evi- say or by using a dipstick test specific for but this approach has not been formallydence suggests that ARBs have a smaller microalbumin, without simultaneously evaluated in prospective trials.magnitude of rise in potassium compared measuring urine creatinine, is somewhat Complications of kidney disease cor-with ACE inhibitors in people with ne- less expensive but susceptible to false- relate with level of kidney function. Whenphropathy (272,273). It is important to negative and -positive determinations as a the eGFR is less than 60 ml min/1.73 m2,note that both ACE inhibitors and ARBs result of variation in urine concentration screening for anemia, malnutrition, andreduce loss of kidney function in people due to hydration and other factors. metabolic bone disease is indicated. Earlywith diabetic nephropathy, above and be- Abnormalities of albumin excretion vaccination against Hepatitis B is indi-yond any such effect attributable to a re- are defined in Table 14. Because of vari- cated in patients likely to progress to end-duction in systemic blood pressure. ability in urinary albumin excretion, two stage kidney disease.Combinations of drugs that block the ren- of three specimens collected within a 3- to Consider referral to a physician expe-nin-angiotensin-aldosterone system (e.g., 6-month period should be abnormal be- rienced in the care of kidney disease whenan ACE inhibitor plus an ARB, a miner- fore considering a patient to have crossed there is uncertainty about the etiology ofalocorticoid antagonist, or a direct renin one of these diagnostic thresholds. Exer- kidney disease (active urine sediment, ab-inhibitor) have been shown to provide ad- cise within 24 h, infection, fever, CHF, sence of retinopathy, or rapid decline inditional lowering of albuminuria (274 – marked hyperglycemia, and marked hy- GFR), difficult management issues, or ad-277). However, the long-term effects of pertension may elevate urinary albumin vanced kidney disease. The threshold forsuch combinations on renal or cardiovas- excretion over baseline values. referral may vary depending on the fre-cular outcomes have not yet been evalu- Information on presence of abnormal quency with which a provider encountersated in clinical trials. urine albumin excretion in addition to diabetic patients with significant kidney Other drugs, such as diuretics, cal- level of GFR may be used to stage CKD. disease. Consultation with a nephrologistcium channel blockers, and -blockers, The National Kidney Foundation classifi- when stage 4 CKD develops has beencare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S35
    • Standards of Medical CareTable 15—Stages of CKD other disorders of the eye occur earlier and more frequently in people with GFR (ml/min per diabetes. 1.73 m2 body In addition to duration of diabetes,Stage Description surface area) other factors that increase the risk of, or are associated with, retinopathy include1 Kidney damage* with normal or increased GFR 90 chronic hyperglycemia (291), the pres-2 Kidney damage* with mildly decreased GFR 60–89 ence of nephropathy (292), and hyper-3 Moderately decreased GFR 30–59 tension (293). Intensive diabetes4 Severely decreased GFR 15–29 management with the goal of achieving5 Kidney failure 15 or dialysis near normoglycemia has been shown in*Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests. Adapted from ref. large prospective randomized studies to283. prevent and/or delay the onset and pro- gression of diabetic retinopathy (53,57,58). Lowering blood pressure hasfound to reduce cost, improve quality of betic retinopathy. Interpretation of the been shown to decrease the progressioncare, and keep people off dialysis longer images should be performed by a of retinopathy (187). Several case series(289,290). However, nonrenal specialists trained eye care provider. While retinal and a controlled prospective study sug-should not delay educating their patients photography may serve as a screening gest that pregnancy in type 1 diabetic pa-about the progressive nature of diabetic tool for retinopathy, it is not a substi- tients may aggravate retinopathykidney disease, the renal preservation tute for a comprehensive eye exam, (294,295); laser photocoagulation sur-benefits of aggressive treatment of blood which should be performed at least ini- gery can minimize this risk (295).pressure, blood glucose, and hyperlipid- tially and at intervals thereafter as rec- One of the main motivations foremia, and the potential need for renal re- ommended by an eye care professional. screening for diabetic retinopathy is theplacement therapy. (E) established efficacy of laser photocoagu- ● Women with preexisting diabetes who lation surgery in preventing vision loss.C. Retinopathy screening and are planning pregnancy or who have Two large trials, the Diabetic Retinopathytreatment become pregnant should have a com- Study (DRS) and the Early Treatment Di- prehensive eye examination and be abetic Retinopathy Study (ETDRS), pro-Recommendations counseled on the risk of development vide the strongest support for the and/or progression of diabetic retinop- therapeutic benefits of photocoagulationGeneral recommendations surgery.● To reduce the risk or slow the progres- athy. Eye examination should occur in the first trimester with close follow-up The DRS (296) showed that panreti- sion of retinopathy, optimize glycemic nal photocoagulation surgery reduced the control. (A) throughout pregnancy and for 1 year postpartum. (B) risk of severe vision loss from PDR from● To reduce the risk or slow the progres- 15.9% in untreated eyes to 6.4% in sion of retinopathy, optimize blood treated eyes. The benefit was greatest pressure control. (A) Treatment among patients whose baseline evalua- ● Promptly refer patients with any level of tion revealed high-risk characteristicsScreening macular edema, severe NPDR, or any (chiefly disc neovascularization or vitre-● Adults and children aged 10 years or PDR to an ophthalmologist who is ous hemorrhage). Given the risks of mod- older with type 1 diabetes should have knowledgeable and experienced in the est loss of visual acuity and contraction of an initial dilated and comprehensive management and treatment of diabetic the visual field from panretinal laser sur- eye examination by an ophthalmologist retinopathy. (A) gery, such therapy is primarily recom- or optometrist within 5 years after the ● Laser photocoagulation therapy is indi- mended for eyes with PDR approaching onset of diabetes. (B) cated to reduce the risk of vision loss in or having high-risk characteristics.● Patients with type 2 diabetes should patients with high-risk PDR, clinically The ETDRS (297) established the have an initial dilated and comprehen- significant macular edema, and in some benefit of focal laser photocoagulation sive eye examination by an ophthalmol- cases of severe NPDR. (A) surgery in eyes with macular edema, ogist or optometrist shortly after the ● The presence of retinopathy is not a particularly those with clinically signif- diagnosis of diabetes. (B) contraindication to aspirin therapy for icant macular edema, with reduction of● Subsequent examinations for type 1 cardioprotection, as this therapy does doubling of the visual angle (e.g., 20/ and type 2 diabetic patients should be not increase the risk of retinal hemor- 50 –20/100) from 20% in untreated repeated annually by an ophthalmolo- rhage. (A) eyes to 8% in treated eyes. The ETDRS gist or optometrist. Less frequent exams also verified the benefits of panretinal (every 2–3 years) may be considered Diabetic retinopathy is a highly specific photocoagulation for high-risk PDR, following one or more normal eye ex- vascular complication of both type 1 and but not for mild or moderate NPDR. In ams. Examinations will be required type 2 diabetes, with prevalence strongly older-onset patients with severe NPDR more frequently if retinopathy is pro- related to duration of diabetes. Diabetic or less-than-high-risk PDR, the risk of gressing. (B) retinopathy is the most frequent cause of severe vision loss or vitrectomy was re-● High-quality fundus photographs can new cases of blindness among adults aged duced 50% by early laser photocoagu- detect most clinically significant dia- 20 –74 years. Glaucoma, cataracts, and lation surgery at these stages.S36 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement Laser photocoagulation surgery in D. Neuropathy screening and monofilament pressure sensation at theboth trials was beneficial in reducing the treatment (306) distal plantar aspect of both great toes andrisk of further vision loss, but generally metatarsal joints, and assessment of ankle Recommendationsnot beneficial in reversing already dimin- ● All patients should be screened for dis- reflexes. Combinations of more than oneished acuity. This preventive effect and test have 87% sensitivity in detecting tal symmetric polyneuropathy (DPN) atthe fact that patients with PDR or macular diagnosis and at least annually thereaf- DPN. Loss of 10-g monofilament percep-edema may be asymptomatic provide ter using simple clinical tests. (B) tion and reduced vibration perceptionstrong support for a screening program to ● Electrophysiological testing is rarely predict foot ulcers (306).detect diabetic retinopathy. needed, except in situations where the b. Diabetic autonomic neuropathy (307). As retinopathy is estimated to take at clinical features are atypical. (E) The symptoms and signs of autonomicleast 5 years to develop after the onset of ● Screening for signs and symptoms of dysfunction should be elicited carefullyhyperglycemia (298), patients with type 1 cardiovascular autonomic neuropathy during the history and physical examina-diabetes should have an initial dilated and should be instituted at diagnosis of type tion. Major clinical manifestations of dia-comprehensive eye examination within 5 2 diabetes and 5 years after the diagno- betic autonomic neuropathy includeyears after the onset of diabetes. Patients sis of type 1 diabetes. Special testing is resting tachycardia, exercise intolerance,with type 2 diabetes who generally have rarely needed and may not affect man- orthostatic hypotension, constipation,had years of undiagnosed diabetes (299) agement or outcomes. (E) gastroparesis, erectile dysfunction, sudo-and who have a significant risk of preva- ● Medications for the relief of specific motor dysfunction, impaired neurovas-lent diabetic retinopathy at the time of symptoms related to DPN and auto- cular function, “brittle diabetes,” anddiabetes diagnosis should have an initial nomic neuropathy are recommended, hypoglycemic autonomic failure.dilated and comprehensive eye examina- as they improve the quality of life of the Cardiovascular autonomic neuropa-tion soon after diagnosis. Examinations patient. (E) thy, a CVD risk factor (93), is the mostshould be performed by an ophthalmolo- studied and clinically important form ofgist or optometrist who is knowledgeable The diabetic neuropathies are heteroge- diabetic autonomic neuropathy. Cardio-and experienced in diagnosing the pres- neous with diverse clinical manifesta- vascular autonomic neuropathy may beence of diabetic retinopathy and is aware tions. They may be focal or diffuse. Most indicated by resting tachycardia ( 100of its management. Subsequent examina- common among the neuropathies are bpm), orthostasis (a fall in systolic bloodtions for type 1 and type 2 diabetic pa- chronic sensorimotor DPN and auto- pressure 20 mmHg upon standingtients are generally repeated annually. nomic neuropathy. Although DPN is a without an appropriate heart rate re-Less frequent exams (every 2–3 years) diagnosis of exclusion, complex investi- sponse), or other disturbances in auto-may be cost effective after one or more gations to exclude other conditions are nomic nervous system function involvingnormal eye exams (300 –302), while ex- rarely needed. the skin, pupils, or gastrointestinal andaminations will be required more fre- The early recognition and appropri- genitourinary systems.quently if retinopathy is progressing. ate management of neuropathy in the pa- Gastrointestinal neuropathies (e.g., tient with diabetes is important for a Examinations can also be done with esophageal enteropathy, gastroparesis, number of reasons: 1) nondiabetic neu-retinal photographs (with or without di- constipation, diarrhea, and fecal incon- ropathies may be present in patients withlation of the pupil) read by experienced diabetes and may be treatable; 2) a num- tinence) are common, and any sectionexperts. In-person exams are still nec- ber of treatment options exist for symp- of the gastrointestinal tract may be af-essary when the photos are unaccept- tomatic diabetic neuropathy; 3) up to fected. Gastroparesis should be sus-able and for follow-up of abnormalities 50% of DPN may be asymptomatic, and pected in individuals with erraticdetected. Photos are not a substitute for patients are at risk of insensate injury to glucose control or with upper gastroin-a comprehensive eye exam, which their feet; 4) autonomic neuropathy may testinal symptoms without other identi-should be performed at least initially involve every system in the body; and 5) fied cause. Evaluation of solid-phaseand at intervals thereafter as recom- cardiovascular autonomic neuropathy gastric emptying using double-isotopemended by an eye care professional. causes substantial morbidity and mortal- scintigraphy may be done if symptomsThis technology has great potential in ity. Specific treatment for the underlying are suggestive, but test results often cor-areas where qualified eye care profes- nerve damage is not currently available, relate poorly with symptoms. Constipa-sionals are not available and may also other than improved glycemic control, tion is the most common lower-enhance efficiency and reduce costs which may slow progression but not re- gastrointestinal symptom but canwhen the expertise of ophthalmologists verse neuronal loss. Effective symptom- alternate with episodes of diarrhea.can be used for more complex examina- atic treatments are available for some Diabetic autonomic neuropathy istions and for therapy (303). manifestations of DPN and autonomic also associated with genitourinary tract Results of eye examinations should neuropathy. disturbances. In men, diabetic autonomicbe documented and transmitted to the neuropathy may cause erectile dysfunc-referring health care professional. For a 1. Diagnosis of neuropathy tion and/or retrograde ejaculation. Evalu-detailed review of the evidence and fur- a. Distal symmetric polyneuropathy. ation of bladder dysfunction should bether discussion of diabetic retinopathy, Patients with diabetes should be screened performed for individuals with diabetessee the ADA technical review and annually for DPN using tests such as pin- who have recurrent urinary tract infec-position statement on this subject prick sensation, vibration perception (us- tions, pyelonephritis, incontinence, or a(304,305). ing a 128-Hz tuning fork), 10-g palpable bladder.care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S37
    • Standards of Medical CareTable 16—Table of drugs to treat symptomatic DPN ● visual impairment ● diabetic nephropathy (especially pa-Class Examples Typical doses* tients on dialysis) ● poor glycemic controlTricyclic drugs Amitriptyline 10–75 mg at bedtime ● cigarette smoking Nortriptyline 25–75 mg at bedtime Imipramine 25–75 mg at bedtime Many studies have been published pro-Anticonvulsants Gabapentin 300–1,200 mg t.i.d. posing a range of tests that might usefully Carbamazepine 200–400 mg t.i.d. identify patients at risk of foot ulceration, Pregabalin† 100 mg t.i.d. creating confusion among practitioners as5-Hydroxytryptamine and Duloxetine† 60–120 mg daily fs to which screening tests should be norepinephrine uptake adopted in clinical practice. An ADA task inhibitor force was therefore assembled in 2008 toSubstance P inhibitor Capsaicin cream 0.025–0.075% applied t.i.d.-q.i.d. concisely summarize recent literature in*Dose response may vary; initial doses need to be low and titrated up. †Has FDA indication for treatment of this area and recommend what should bepainful diabetic neuropathy. included in the comprehensive foot exam for adult patients with diabetes. Their rec- ommendations are summarized below,2. Symptomatic treatments for loss of protective sensation (LOPS) but clinicians should refer to the task (10-g monofilament plus testing anya. Distal symmetric polyneuropathy. force report (308) for further details and one of: vibration using 128-Hz tuningThe first step in management of patients practical descriptions of how to perform fork, pinprick sensation, ankle reflexes,with DPN should be to aim for stable and components of the comprehensive foot or vibration perception threshold). (B)optimal glycemic control. Although con- ● Provide general foot self-care education examination.trolled trial evidence is lacking, several to all patients with diabetes. (B) At least annually, all adults with dia-observational studies suggest that neuro- ● betes should undergo a comprehensive A multidisciplinary approach is recom-pathic symptoms improve not only with foot examination to identify high-risk mended for individuals with foot ulcersoptimization of control, but also with the conditions. Clinicians should ask about and high-risk feet, especially those withavoidance of extreme blood glucose fluc- history of previous foot ulceration or am- a history of prior ulcer or amputation.tuations. Patients with painful DPN may putation, neuropathic or peripheral vas- (B)benefit from pharmacological treatment ● Refer patients who smoke, have LOPS cular symptoms, impaired vision, tobaccoof their symptoms: many agents have ef- and structural abnormalities, or have use, and foot care practices. A general in-ficacy confirmed in published random- history of prior lower-extremity com- spection of skin integrity and musculo-ized controlled trials, with several FDA- plications to foot care specialists for on- skeletal deformities should be done in aapproved for the management of painful going preventive care and life-long well-lit room. Vascular assessment wouldDPN. See Table 16 for examples of agents surveillance. (C) include inspection and assessment ofto treat DPN pain. ● pedal pulses. Initial screening for peripheral arterialb. Diabetic autonomic neuropathy. Gas- The neurologic exam recommended disease (PAD) should include a historytroparesis symptoms may improve with is designed to identify LOPS rather than for claudication and an assessment ofdietary changes and prokinetic agents early neuropathy. The clinical examina- the pedal pulses. Consider obtaining ansuch as metoclopramide or erythromycin. tion to identify LOPS is simple and re- ankle-brachial index (ABI), as many pa-Treatments for erectile dysfunction may quires no expensive equipment. Five tients with PAD are asymptomatic. (C)include phosphodiesterase type 5 inhibi- ● simple clinical tests (use of a 10-g mono- Refer patients with significant claudica-tors, intracorporeal or intraurethral pros- filament, vibration testing using a 128-Hz tion or a positive ABI for further vascu-taglandins, vacuum devices, or penile tuning fork, tests of pinprick sensation, lar assessment and consider exercise,prostheses. Interventions for other mani- ankle reflex assessment, and testing vibra- medications, and surgical options. (C)festations of autonomic neuropathy are tion perception threshold with a biothesi-described in the ADA statement on neu- Amputation and foot ulceration, conse- ometer), each with evidence from well-ropathy (306). As with DPN treatments, quences of diabetic neuropathy and/or conducted prospective clinical cohortthese interventions do not change the un- PAD, are common and major causes of studies, are considered useful in the diag-derlying pathology and natural history of morbidity and disability in people with nosis of LOPS in the diabetic foot. Thethe disease process but may have a posi- diabetes. Early recognition and manage- task force agrees that any of the five teststive impact on the quality of life of the ment of risk factors can prevent or delay listed could be used by clinicians to iden-patient. adverse outcomes. tify LOPS, although ideally two of these The risk of ulcers or amputations is should be regularly performed during theE. Foot care increased in people who have the follow- screening exam—normally the 10-gRecommendations ing risk factors: monofilament and one other test. One or● For all patients with diabetes, perform more abnormal tests would suggest an annual comprehensive foot exami- ● previous amputation LOPS, while at least two normal tests (and nation to identify risk factors predictive ● past foot ulcer history no abnormal test) would rule out LOPS. of ulcers and amputations. The foot ex- ● peripheral neuropathy The last test listed, vibration assessment amination should include inspection, ● foot deformity using a biothesiometer or similar instru- assessment of foot pulses, and testing ● peripheral vascular disease ment, is widely used in the U.S.; however,S38 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementidentification of the patient with LOPS modated with commercial therapeutic will evolve according to, physical, psy-can easily be carried out without this or footwear may need custom-molded chological, and emotional maturity. MNTother expensive equipment. shoes. should be provided at diagnosis, and at Initial screening for PAD should in- Foot ulcers and wound care may re- least annually thereafter, by an individualclude a history for claudication and an quire care by a podiatrist, orthopedic experienced with the nutritional needs ofassessment of the pedal pulses. A diagnos- or vascular surgeon, or rehabilitation the growing child and the behavioral is-tic ABI should be performed in any pa- specialist experienced in the manage- sues that have an impact on adolescenttient with symptoms of PAD. Due to the ment of individuals with diabetes. For a diets, including risk for disordered eating.high estimated prevalence of PAD in pa- complete discussion, see the ADA con-tients with diabetes and the fact that sensus statement on diabetic foot wound a. Glycemic controlmany patients with PAD are asymptom- care (310). Recommendationsatic, an ADA consensus statement on ● Consider age when setting glycemicPAD (309) suggested that a screening VII. DIABETES CARE IN goals in children and adolescents withof ABI be performed in patients over SPECIFIC POPULATIONS type 1 diabetes, with less stringent goals50 years of age and considered in patients for younger children. (E)under 50 years of age who have other A. Children and adolescentsPAD risk factors (e.g., smoking, hyperten- While current standards for diabetession, hyperlipidemia, or duration of dia- management reflect the need to maintain 1. Type 1 diabetes glucose control as near to normal as safelybetes 10 years). Refer patients with Three-quarters of all cases of type 1 dia-significant symptoms or a positive ABI possible, special consideration must be betes are diagnosed in individuals 18 given to the unique risks of hypoglycemiafor further vascular assessment and con- years of age. Because children are not sim-sider exercise, medications, and surgical in young children. Glycemic goals need to ply “small adults,” it is appropriate to con- be modified to take into account the factoptions (309). sider the unique aspects of care and Patients with diabetes and high-risk that most children 6 or 7 years of age management of children and adolescents have a form of “hypoglycemic unaware-foot conditions should be educated re- with type 1 diabetes. Children with dia-garding their risk factors and appropriate ness.” Their counterregulatory mecha- betes differ from adults in many respects, nisms are immature and they may lack themanagement. Patients at risk should un- including changes in insulin sensitivity cognitive capacity to recognize and re-derstand the implications of the LOPS, related to sexual maturity and physical spond to hypoglycemic symptoms, plac-the importance of foot monitoring on a growth, ability to provide self-care, super- ing them at greater risk for severedaily basis, the proper care of the foot in- vision in child care and school, and hypoglycemia and its sequelae. In addi-cluding nail and skin care, and the selec- unique neurologic vulnerability to hypo- tion, and unlike the case in adults, youngtion of appropriate footwear. Patients glycemia and DKA. Attention to such is- children under the age of 5 years are atwith LOPS should be educated on ways to sues as family dynamics, developmental risk for permanent cognitive impairmentsubstitute other sensory modalities (hand stages, and physiologic differences related after episodes of severe hypoglycemiapalpation, visual inspection) for surveil- to sexual maturity are all essential in de- (312–314). Extensive evidence indicateslance of early foot problems. Patients’ un- veloping and implementing an optimal that near normalization of blood glucosederstanding of these issues and their diabetes regimen. Although recommen- levels is seldom attainable in children andphysical ability to conduct proper foot dations for children and adolescents are adolescents after the honeymoon (remis-surveillance and care should be assessed. less likely to be based on clinical trial ev- sion) period. The A1C level achieved inPatients with visual difficulties, physical idence, because of current and historical the “intensive” adolescent cohort of theconstraints preventing movement, or cog- restraints placed on conducting research DCCT group was 1% higher than thatnitive problems that impair their ability to in children, expert opinion and a review achieved by adult DCCT subjects andassess the condition of the foot and to in- of available and relevant experimental above current ADA recommendations forstitute appropriate responses will need data are summarized in the ADA state- patients in general. However, the in-other people, such as family members, to ment on care of children and adolescents creased frequency of use of basal bolusassist in their care. with type 1 diabetes (311). regimens (including insulin pumps) in People with neuropathy or evidence Ideally, the care of a child or adoles- youth from infancy through adolescenceof increased plantar pressure (e.g., ery- cent with type 1 diabetes should be pro- has been associated with more childrenthema, warmth, callus, or measured pres- vided by a multidisciplinary team of reaching ADA blood glucose targetssure) may be adequately managed with specialists trained in the care of children (315,316) in those families in which bothwell-fitted walking shoes or athletic with pediatric diabetes. At the very least, parents and the child with diabetes areshoes that cushion the feet and redis- education of the child and family should motivated to perform the required diabe-tribute pressure. Callus can be debrided be provided by health care providers tes-related tasks.with a scalpel by a foot care specialist or trained and experienced in childhood di- In selecting glycemic goals, the bene-other health professional with experience abetes and sensitive to the challenges fits on long-term health outcomes ofand training in foot care. People with posed by diabetes in this age-group. At achieving a lower A1C must be weighedbony deformities (e.g., hammertoes, the time of initial diagnosis, it is essential against the unique risks of hypoglycemiaprominent metatarsal heads, or bunions) that diabetes education be provided in a and the difficulties achieving near-may need extra-wide or -depth shoes. timely fashion, with the expectation that normoglycemia in children and youth.People with extreme bony deformities the balance between adult supervision Age-specific glycemic and A1C goals are(e.g., Charcot foot) who cannot be accom- and self-care should be defined by, and presented in Table 17.care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S39
    • Standards of Medical CareTable 17—Plasma blood glucose and A1C goals for type 1 diabetes by age-group Plasma blood glucose goal range (mg/dl) Bedtime/Values by age (years) Before meals overnight A1C RationaleToddlers and preschoolers (0–6) 100–180 110–200 8.5% (but 7.5%) High risk and vulnerability to hypoglycemiaSchool age (6–12) 90–180 100–180 8% Risks of hypoglycemia and relatively low risk of complications prior to pubertyAdolescents and young adults (13–19) 90–130 90–150 7.5% Risk of severe hypoglycemia Developmental and psychological issues A lower goal ( 7.0%) is reasonable if it can be achieved without excessive hypoglycemiaKey concepts in setting glycemic goals: ● Goals should be individualized and lower goals may be reasonable based on benefit-risk assessment. ● Blood glucose goals should be higher than those listed above in children with frequent hypoglycemia or hypoglycemia unawareness. ● Postprandial blood glucose values should be measured when there is a discrepancy between pre-prandial blood glucose values and A1C levels and to help assess glycemia in those on basal/bolus regimens.b. Screening and management of ● ACE inhibitors should be considered profile performed soon after diagnosischronic complications in children and for the initial treatment of hyperten- (after glucose control has been estab-adolescents with type 1 diabetes sion. (E) lished). (E) ● The goal of treatment is a blood pres- ● For both age-groups, if lipids are abnor-i. Nephropathy sure consistently 130/80 or below the mal, annual monitoring is recom- 90th percentile for age, sex, and height, mended. If LDL cholesterol values areRecommendations whichever is lower. (E) within the accepted risk levels ( 100● Annual screening for microalbumin- mg/dl [2.6 mmol/l]), a lipid profile uria, with a random spot urine sample Hypertension in childhood is defined as should be repeated every 5 years. (E) for microalbumin-to-creatinine ratio, an average systolic or diastolic blood pres- should be initiated once the child is 10 sure 95th percentile for age, sex, and Treatment years of age and has had diabetes for 5 ● Initial therapy should consist of optimi- height percentile measured on at least years. (E) three separate days. “High-normal” blood zation of glucose control and MNT us-● Confirmed, persistently elevated mi- pressure is defined as an average systolic ing a Step II AHA diet aimed at a croalbumin levels on two additional decrease in the amount of saturated fat or diastolic blood pressure 90th but urine specimens should be treated with in the diet. (E) 95th percentile for age, sex, and height an ACE inhibitor, titrated to normaliza- ● After the age of 10 years, the addition of percentile measured on at least 3 separate tion of microalbumin excretion if pos- days. Normal blood pressure levels for a statin is recommended in patients sible. (E) age, sex, and height and appropriate who, after MNT and lifestyle changes,ii. Hypertension methods for determinations are available have LDL cholesterol 160 mg/dl (4.1 online at www.nhlbi.nih.gov/health/ mmol/l) or LDL cholesterol 130Recommendations prof/heart/hbp/hbp_ped.pdf. mg/dl (3.4 mmol/l) and one or more● Treatment of high-normal blood pres- CVD risk factors. (E) sure (systolic or diastolic blood pres- ● The goal of therapy is an LDL choles- iii. Dyslipidemia sure consistently above the 90th terol value 100 mg/dl (2.6 mmol/l). percentile for age, sex, and height) (E) Recommendations should include dietary intervention and exercise aimed at weight control Screening People diagnosed with type 1 diabetes in and increased physical activity, if ap- ● If there is a family history of hypercho- childhood have a high risk of early sub- propriate. If target blood pressure is not lesterolemia (total cholesterol 240 clinical (317–319) and clinical (320) reached with 3– 6 months of lifestyle mg/dl) or a cardiovascular event before CVD. Although intervention data are intervention, pharmacologic treatment age 55 years, or if family history is un- lacking, the AHA categorizes type 1 dia- should be initiated. (E) known, then a fasting lipid profile betic children in the highest tier for car-● Pharmacologic treatment of hyperten- should be performed on children 2 diovascular risk and recommends both sion (systolic or diastolic blood pres- years of age soon after diagnosis (after lifestyle and pharmacologic treatment for sure consistently above the 95th glucose control has been established). those with elevated LDL cholesterol levels percentile for age, sex, and height or If family history is not of concern, then (321,322). Initial therapy should be with consistently 130/80 mmHg, if 95% the first lipid screening should be per- a Step II AHA diet, which restricts satu- exceeds that value) should be initiated formed at puberty ( 10 years). All chil- rated fat to 7% of total calories and re- as soon as the diagnosis is confirmed. dren diagnosed with diabetes at or after stricts dietary cholesterol to 200 mg per (E) puberty should have a fasting lipid day. Data from randomized clinical trialsS40 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementin children as young as 7 months of age odic rescreening of asymptomatic indi- into adolescence. Health care providersindicate that this diet is safe and does not viduals. (E) who care for children and adolescentsinterfere with normal growth and devel- ● Children with positive antibodies therefore must be capable of evaluatingopment (323,324). should be referred to a gastroenterolo- the behavioral, emotional, and psychoso- For children over the age of 10 years gist for evaluation. (E) cial factors that interfere with implemen-with persistent elevation of LDL choles- ● Children with confirmed celiac disease tation and then must work with theterol despite lifestyle therapy, statins should have consultation with a dieti- individual and family to resolve problemsshould be considered. Neither long-term tian and be placed on a gluten-free diet. that occur and/or to modify goals assafety nor cardiovascular outcome effi- (E) appropriate.cacy has been established for children. d. School and day care. Since a sizableHowever, recent studies have shown Celiac disease is an immune-mediated portion of a child’s day is spent in school,short-term safety equivalent to that seen disorder that occurs with increased fre- close communication with school or dayin adults and efficacy in lowering LDL quency in patients with type 1 diabetes care personnel is essential for optimal di-cholesterol levels, improving endothelial (1–16% of individuals compared with abetes management, safety, and maximalfunction, and causing regression of ca- 0.3–1% in the general population) academic opportunities. See VIII.B. Dia-rotid intimal thickening (325–327). No (328,329). Symptoms of celiac disease in- betes Care in the School and Day Carestatin is approved for use under the age of clude diarrhea, weight loss or poor weight10 years, and statin treatment should gen- gain, growth failure, abdominal pain, Setting, for further discussion.erally not be used in type 1 diabetic chil- chronic fatigue, malnutrition due to mal-dren prior to this age. absorption, other gastrointestinal prob- lems, and unexplained hypoglycemia or 2. Type 2 diabetesiv. Retinopathy erratic blood glucose concentrations. The incidence of type 2 diabetes in ado- lescents is increasing, especially in ethnicRecommendations vi. Hypothyroidism minority populations (21). Distinction● The first ophthalmologic examination between type 1 and type 2 diabetes in should be obtained once the child is 10 Recommendations children can be difficult, since the preva- years of age and has had diabetes for ● Children with type 1 diabetes should be lence of overweight in children continues 3–5 years. (E) screened for thyroid peroxidase and to rise and since autoantigens and ketosis● After the initial examination, annual thyroglobulin antibodies at diagnosis. may be present in a substantial number of routine follow-up is generally recom- (E) patients with features of type 2 diabetes mended. Less frequent examinations ● Thyroid-stimulating hormone (TSH) (including obesity and acanthosis nigri- may be acceptable on the advice of an concentrations should be measured af- cans). Such a distinction at the time of eye care professional. (E) ter metabolic control has been estab- diagnosis is critical because treatment lished. If normal, they should be regimens, educational approaches, andAlthough retinopathy most commonly rechecked every 1–2 years or if the pa- dietary counsel will differ markedly be-occurs after the onset of puberty and after tient develops symptoms of thyroid tween the two diagnoses.5–10 years of diabetes duration, it has dysfunction, thyromegaly, or an abnor- Type 2 diabetes has a significant in-been reported in prepubertal children mal growth rate. Free T4 should be cidence of comorbidities alreadyand with diabetes duration of only 1–2 measured if TSH is abnormal. (E) present at the time of diagnosis (334). Ityears. Referrals should be made to eye is recommended that blood pressurecare professionals with expertise in dia- Autoimmune thyroid disease is the most measurement, a fasting lipid profile,betic retinopathy, an understanding of common autoimmune disorder associ- microalbuminuria assessment, and di-the risk for retinopathy in the pediatric ated with diabetes, occurring in 17–30% lated eye examination be performed atpopulation, and experience in counseling of patients with type 1 diabetes (330). The the time of diagnosis. Thereafter,the pediatric patient and family on the presence of thyroid auto-antibodies is screening guidelines and treatment rec-importance of early prevention/inter- predictive of thyroid dysfunction, gener- ommendations for hypertension, dys-vention. ally hypothyroidism and less commonly lipidemia, microalbuminuria, and hyperthyroidism (331). Subclinical hy- retinopathy in youth with type 2 diabe-v. Celiac disease pothyroidism may be associated with in- creased risk of symptomatic tes are similar to those for youth withRecommendations hypoglycemia (332) and with reduced type 1 diabetes. Additional problems● Children with type 1 diabetes should be linear growth (333). Hyperthyroidism al- that may need to be addressed include screened for celiac disease by measuring ters glucose metabolism, potentially re- polycystic ovary disease and the various tissue transglutaminase or anti- sulting in deterioration of metabolic comorbidities associated with pediatric endomysial antibodies, with documenta- control. obesity such as sleep apnea, hepatic ste- tion of normal serum IgA levels, soon c. Self-management. No matter how atosis, orthopedic complications, and after the diagnosis of diabetes. (E) sound the medical regimen, it can only be psychosocial concerns. The ADA con-● Testing should be repeated if growth as good as the ability of the family and/or sensus statement on this subject (23) failure, failure to gain weight, weight individual to implement it. Family in- provides guidance on the prevention, loss, or gastroenterologic symptoms oc- volvement in diabetes remains an impor- screening, and treatment of type 2 dia- cur. (E) tant component of optimal diabetes betes and its comorbidities in young● Consideration should be given to peri- management throughout childhood and people.care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S41
    • Standards of Medical CareB. Preconception care 1.7% of infants) was much lower than the betic agents in the preconception period incidence in women who did not partici- must be carefully weighed, recognizingRecommendations pate (range 1.4 –10.9% of infants). One that data are insufficient to establish the● A1C levels should be as close to normal limitation of these studies is that partici- safety of these agents in pregnancy. as possible ( 7%) in an individual pa- pation in preconception care was self- For further discussion of preconcep- tient before conception is attempted. selected rather than randomized. Thus, it tion care, see the related ADA consensus (B) is impossible to be certain that the lower statement (76) and position statement● Starting at puberty, preconception malformation rates resulted fully from (341) on preexisting diabetes and counseling should be incorporated in improved diabetes care. Nonetheless, the pregnancy. the routine diabetes clinic visit for all evidence supports the concept that mal- women of child-bearing potential. (C) formations can be reduced or prevented C. Older adults● Women with diabetes who are contem- by careful management of diabetes before plating pregnancy should be evaluated pregnancy. Recommendations and, if indicated, treated for diabetic Planned pregnancies greatly facilitate ● Older adults who are functional, are retinopathy, nephropathy, neuropathy, preconception diabetes care. Unfortu- cognitively intact, and have significant and CVD. (E) nately, nearly two-thirds of pregnancies life expectancy should receive diabetes● Medications used by such women in women with diabetes are unplanned, care using goals developed for younger should be evaluated prior to concep- leading to a persistent excess of malfor- adults. (E) tion because drugs commonly used to mations in infants of diabetic mothers. To ● Glycemic goals for older adults not treat diabetes and its complications minimize the occurrence of these devas- meeting the above criteria may be re- may be contraindicated or not recom- tating malformations, standard care for all laxed using individual criteria, but hy- mended in pregnancy, including st- women with diabetes who have child- perglycemia leading to symptoms or atins, ACE inhibitors, ARBs, and most bearing potential, beginning at the onset risk of acute hyperglycemic complica- noninsulin therapies. (E) of puberty or at diagnosis, should include tions should be avoided in all patients. 1) education about the risk of malforma- (E)Major congenital malformations remain tions associated with unplanned pregnan- ● Other cardiovascular risk factorsthe leading cause of mortality and serious cies and poor metabolic control; and 2) should be treated in older adults withmorbidity in infants of mothers with type use of effective contraception at all times, consideration of the time frame of ben-1 or type 2 diabetes. Observational stud- unless the patient has good metabolic efit and the individual patient. Treat-ies indicate that the risk of malformations control and is actively trying to conceive. ment of hypertension is indicated inincreases continuously with increasing Women contemplating pregnancy virtually all older adults, and lipid andmaternal glycemia during the first 6 – 8 need to be seen frequently by a multidis- aspirin therapy may benefit those withweeks of gestation, as defined by first- ciplinary team experienced in the man- life expectancy at least equal to the timetrimester A1C concentrations. There is no agement of diabetes before and during frame of primary or secondary preven-threshold for A1C values below which pregnancy. The goals of preconception tion trials. (E)risk disappears entirely. However, mal- care are to 1) involve and empower the ● Screening for diabetes complicationsformation rates above the 1–2% back- patient in the management of her diabe- should be individualized in olderground rate of nondiabetic pregnancies tes, 2) achieve the lowest A1C test results adults, but particular attention shouldappear to be limited to pregnancies in possible without excessive hypoglycemia, be paid to complications that wouldwhich first-trimester A1C concentrations 3) assure effective contraception until sta- lead to functional impairment. (E)are 1% above the normal range for a ble and acceptable glycemia is achieved,nondiabetic pregnant woman. and 4) identify, evaluate, and treat long- Diabetes is an important health condition Preconception care of diabetes ap- term diabetes complications such as reti- for the aging population; at least 20% ofpears to reduce the risk of congenital mal- nopathy, nephropathy, neuropathy, patients over the age of 65 years have di-formations. Five nonrandomized studies hypertension, and CHD (76). abetes, and this number can be expectedcompared rates of major malformations in Among the drugs commonly used in to grow rapidly in the coming decades.infants between women who participated the treatment of patients with diabetes, a Older individuals with diabetes havein preconception diabetes care programs number may be relatively or absolutely higher rates of premature death, func-and women who initiated intensive diabe- contraindicated during pregnancy. St- tional disability, and coexisting illnessestes management after they were already atins are category X (contraindicated for such as hypertension, CHD, and strokepregnant. The preconception care pro- use in pregnancy) and should be discon- than those without diabetes. Older adultsgrams were multidisciplinary and de- tinued before conception, as should ACE with diabetes are also at greater risk thansigned to train patients in diabetes self- inhibitors (340). ARBs are category C other older adults for several common ge-management with diet, intensified insulin (risk cannot be ruled out) in the first tri- riatric syndromes, such as polypharmacy,therapy, and SMBG. Goals were set to mester but category D (positive evidence depression, cognitive impairment, uri-achieve normal blood glucose concentra- of risk) in later pregnancy and should nary incontinence, injurious falls, andtions, and 80% of subjects achieved generally be discontinued before preg- persistent pain.normal A1C concentrations before they nancy. Among the oral antidiabetic The American Geriatric Society’sbecame pregnant (335–339). In all five agents, metformin and acarbose are clas- guidelines for improving the care of thestudies, the incidence of major congenital sified as category B (no evidence of risk in older person with diabetes (342) have in-malformations in women who partici- humans) and all others as category C. Po- fluenced the following discussion andpated in preconception care (range 1.0 – tential risks and benefits of oral antidia- recommendations. The care of olderS42 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementadults with diabetes is complicated by adults whose life expectancies equal or agement of CFRD will be found in thetheir clinical and functional heterogene- exceed the time frames seen in clinical consensus report to be published in 2010.ity. Some older individuals developed di- trials.abetes years earlier and may have Special care is required in prescribing VIII. DIABETES CARE INsignificant complications; others who are and monitoring pharmacologic therapy in SPECIFIC SETTINGSnewly diagnosed may have had years of older adults. Metformin is often contrain-undiagnosed diabetes with resultant com- dicated because of renal insufficiency or Diabetes care in the hospitalplications or may have few complications significant heart failure. TZDs can causefrom the disease. Some older adults with fluid retention, which may exacerbate or Recommendationsdiabetes are frail and have other underly- lead to heart failure. They are contraindi- ● All patients with diabetes admitted toing chronic conditions, substantial diabe- cated in patients with CHF (New York the hospital should have their diabetestes-related comorbidity, or limited Heart Association class III and IV), and if clearly identified in the medical record.physical or cognitive functioning. Other used at all should be used very cautiously (E)older individuals with diabetes have little in those with, or at risk for, milder degrees ● All patients with diabetes should havecomorbidity and are active. Life expectan- of CHF. Sulfonylureas, other insulin an order for blood glucose monitoring,cies are highly variable for this population secretagogues, and insulin can cause hy- with results available to all members ofbut often longer than clinicians realize. poglycemia. Insulin use requires that pa- the health care team. (E)Providers caring for older adults with di- tients or caregivers have good visual and ● Goals for blood glucose levelsabetes must take this heterogeneity into motor skills and cognitive ability. Drugs ● Critically ill patients: Insulin therapyconsideration when setting and prioritiz- should be started at the lowest dose and should be initiated for treatment ofing treatment goals. titrated up gradually until targets are persistent hyperglycemia starting at a There are few long-term studies in reached or side effects develop. threshold of 180 mg/dl (10 mmol/older adults that demonstrate the benefits Screening for diabetes complications l). Once insulin therapy is started, aof intensive glycemic, blood pressure, and in older adults also should be individual- glucose range of 140 –180 mg/dllipid control. Patients who can be ex- ized. Particular attention should be paid (7.8 –10 mmol/l) is recommendedpected to live long enough to reap the to complications that can develop over for the majority of critically ill pa-benefits of long-term intensive diabetes short periods of time and/or that would tients. (A) These patients require anmanagement and who are active, have significantly impair functional status, intravenous insulin protocol that hasgood cognitive function, and are willing such as vision and lower-extremity demonstrated efficacy and safety inshould be provided with the needed edu- complications. achieving the desired glucose rangecation and skills to do so and be treated without increasing risk for severe hy-using the goals for younger adults with poglycemia. (E)diabetes. D. Cystic fibrosis–related diabetes ● Non– critically ill patients: There is For patients with advanced diabetes Cystic fibrosis-related diabetes (CFRD) is no clear evidence for specific bloodcomplications, life-limiting comorbid ill- the most common comorbidity in people glucose goals. If treated with insulin,ness, or substantial cognitive or func- with cystic fibrosis, occurring in 20% of the premeal blood glucose targettional impairment, it is reasonable to set adolescents and 40 –50% of adults. The should generally be 140 mg/dl (7.8less-intensive glycemic target goals. These additional diagnosis of diabetes in this mmol/l) with random blood glucosepatients are less likely to benefit from re- population is associated with worse nutri- 180 mg/dl (10.0 mmol/l), providedducing the risk of microvascular compli- tional status, more severe inflammatory these targets can be safely achieved.cations and more likely to suffer serious lung disease, and greater mortality from More stringent targets may be appro-adverse effects from hypoglycemia. How- respiratory failure. For reasons that are priate in stable patients with previousever, patients with poorly controlled not well understood, women with CFRD tight glycemic control. Less stringentdiabetes may be subject to acute compli- are particularly vulnerable to excess mor- targets may be appropriate in thosecations of diabetes, including dehydra- bidity and mortality. Insulin insufficiency with severe comorbidites. (E)tion, poor wound healing, and related to partial fibrotic destruction of ● Scheduled subcutaneous insulin withhyperglycemic hyperosmolar coma. Gly- the islet mass is the primary defect in basal, nutritional, and correction com-cemic goals at a minimum should avoid CFRD. Genetically determined function ponents is the preferred method forthese consequences. of the remaining -cells and insulin resis- achieving and maintaining glucose Although control of hyperglycemia tance associated with infection and in- control in noncritically ill patients. (C)may be important in older individuals flammation may also play a role. Using correction dose or “supplemen-with diabetes, greater reductions in mor- Encouraging new data suggest that early tal” insulin to correct premeal hyper-bidity and mortality may result from con- detection and aggressive insulin therapy glycemia in addition to scheduledtrol of other cardiovascular risk factors have narrowed the gap in mortality be- prandial and basal insulin is recom-rather than from tight glycemic control tween cystic fibrosis patients with and mended. (E)alone. There is strong evidence from clin- without diabetes and have eliminated the ● Glucose monitoring should be initiatedical trials of the value of treating hyper- sex difference in mortality. in any patient not known to be diabetictension in the elderly (343,344). There is A consensus conference on CFRD who receives therapy associated withless evidence for lipid-lowering and aspi- was cosponsored in 2009 by ADA, the high risk for hyperglycemia, includingrin therapy, although the benefits of these Cystic Fibrosis Foundation, and the Law- high-dose glucocorticoid therapy, initi-interventions for primary and secondary son Wilkins Pediatric Endocrine Society. ation of enteral or parenteral nutrition,prevention are likely to apply to older Recommendations for the clinical man- or other medications such as octreotidecare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S43
    • Standards of Medical Care or immunosuppressive medications. glycemia-provoking agents such as glu- of this study lie in stark contrast to a fa- (B) If hyperglycemia is documented cocorticoids or vasopressors. mous 2001 single-center study that re- and persistent, treatment is necessary. People with diabetes are more likely ported a 42% relative reduction in Such patients should be treated to the to be hospitalized and to have longer intensive care unit (ICU) mortality in crit- same glycemic goals as patients with lengths of stay than those without diabe- ically ill surgical patients treated to a tar- known diabetes. (E) tes. A recent survey estimated that 22% of get blood glucose of 80 –110 mg/dl.● A plan for treating hypoglycemia all hospital inpatient days were incurred Importantly, the control group in NICE- should be established for each patient. by people with diabetes and that hospital SUGAR had reasonably good blood glu- Episodes of hypoglycemia in the hospi- inpatient care accounted for one-half of cose management, maintained at a mean tal should be tracked. (E) the $174 billion total U.S. medical expen- glucose of 144 mg/dl, only 29 mg/dl● All patients with diabetes admitted to ditures for this disease (347). This is due, above the intensively managed patients. the hospital should have an A1C ob- in part, to the continued expansion of the Accordingly, this study’s findings do not tained if the result of testing in the pre- worldwide epidemic of type 2 diabetes. In disprove the notion that glycemic control vious 2–3 months is not available. (E) the U.S. alone, there are 1.6 million new in the ICU is important. However, they do● Patients with hyperglycemia in the hos- cases of diabetes each year with an overall strongly suggest that it is not necessary to pital who do not have a diagnosis of prevalence of 23.6 million people (7.8% target blood glucose values 140 mg/dl diabetes should have appropriate plans of the population, with one-quarter of and that a highly stringent target of 110 for follow-up testing and care docu- cases remaining undiagnosed). An addi- mg/dl actually may be dangerous. mented at discharge. (E) tional 57 million American adults are at In a recent meta-analysis of 26 trials high risk for type 2 diabetes (348). While (N 13,567), which included the NICE-The subject of diabetes in the hospital is the costs of illness-related stress hypergly- SUGAR data, the pooled relative risk (RR)extensively reviewed in an ADA technical cemia are not known, they are likely to be of death with intensive insulin therapyreview (345). A recent updated consensus significant given the poor prognosis of was 0.93 as compared with conventionalstatement by the American Association of such patients (349 –352). therapy (95% CI 0.83–1.04) (358). Ap-Clinical Endocrinologists (AACE) and the There is substantial observational ev- proximately half of these trials reportedADA (346) form the basis for the discus- idence linking hyperglycemia in hospital- hypoglycemia, with a pooled RR of inten-sion and guidelines in this section. ized patients (with or without diabetes) to sive therapy of 6.0 (95% CI 4.5– 8.0). The The literature on hospitalized pa- poor outcomes. Cohort studies as well as specific ICU setting influenced the find-tients with hyperglycemia typically de- a few early randomized controlled trials ings, with patients in surgical ICUs ap-scribes three categories: (RCTs) suggested that intensive treatment pearing to benefit from intensive insulin of hyperglycemia improved hospital out- therapy (RR 0.63 [95% CI 0.44 – 0.91]),● Medical history of diabetes: diabetes pre- comes (345,351,352). Interventions to while those in other critical care settings viously diagnosed and acknowledged by normalize glycemia, however, have had did not (medical ICU: 1.0 [0.78 –1.28]; the patient’s treating physician. inconsistent results. Indeed, recent trials “mixed” ICU: 0.99 [0.86 –1.12]). It was● Unrecognized diabetes: hyperglycemia in critically ill patients have failed to show concluded that overall, intensive insulin (fasting blood glucose 126 mg/dl or a significant improvement in mortality therapy increased the risk of hypoglyce- random blood glucose 200 mg/dl) with intensive glycemic control mia but provided no overall benefit on occurring during hospitalization and (353,354) or have even shown increased mortality in the critically ill, although a confirmed as diabetes after hospitaliza- mortality risk (355). Moreover, these re- benefit to patients admitted to the surgical tion by standard diagnostic criteria but cent RCTs have highlighted the risk of se- ICU was suggested. unrecognized as diabetes by the treat- vere hypoglycemia resulting from such It is very clear that the management of ing physician during hospitalization. efforts (353–358). hyperglycemia in the hospital presents● Hospital-related hyperglycemia: hyper- The largest study to date, NICE- unique challenges that stem from varia- glycemia (fasting blood glucose 126 SUGAR, a multicenter, multinational tions in a patient’s nutritional status and mg/dl or random blood glucose 200 RCT, tested the effect of tight glycemic level of consciousness, the practical limi- mg/dl) occurring during the hospital- control (target 81–108 mg/dl) on out- tations of intermittent glycemic monitor- ization that reverts to normal after hos- comes among 6,104 critically ill partici- ing, and the ultimate importance of pital discharge. pants, the majority of whom ( 95%) patient safety. Accordingly, reasonable required mechanical ventilation (355). glucose targets in the hospital setting areThe management of hyperglycemia in the Ninety-day mortality was significantly modestly higher than may be routinelyhospital has logically been considered higher in the intensive versus the conven- advised in patients with diabetes in thesecondary in importance to the condition tional group (target 144 –180 mg/dl) (78 outpatient setting. The following recom-that prompted admission (345). How- more deaths; 27.5 vs. 24.9%, P 0.02) in mendations represent a synthesis of theever, a body of literature now supports both surgical and medical patients. Mor- evidence base over the past decade andtargeted glucose control in the hospital tality from cardiovascular causes was are somewhat less stringent than priorsetting for potential improved clinical more common in the intensive group (76 recommendations of the ADA Standardsoutcomes. Hyperglycemia in the hospital more deaths; 41.6 vs. 35.8%; P 0.02). of Medical Care in Diabetes. For a com-may result from stress; decompensation Severe hypoglycemia was also more com- prehensive review of these data, theof type 1, type 2, or other forms of dia- mon in the intensively treated group (6.8 reader is referred to the latest consensusbetes; and/or may be iatrogenic due to vs. 0.5%; P 0.001). The precise reason statement from AACE and ADA on inpa-withholding of antihyperglycemic for the increased mortality in the tightly tient management of hyperglycemiamedications or administration of hyper- controlled group is unknown. The results (346).S44 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement1. Glycemic targets in hospitalized with random blood glucose 180 mg/dl Continued education of staff with peri-patients (10.0 mmol/l), as long as these targets can odic ongoing review of patient data area. Definition of glucose abnormalities in be safely achieved. To avoid hypoglyce- critical for successful implementation ofthe hospital setting. Hyperglycemia has mia, consideration should be given to re- any insulin protocol (364 –366).been defined as any blood glucose 140 assessing the insulin regimen if blood Patients who receive intravenous in-mg/dl (7.8 mmol/l). Levels that are signif- glucose levels fall below 100 mg/dl (5.6 sulin infusion will usually require transi-icantly and persistently above this may re- mmol/l). Modification of the regimen is tion to subcutaneous insulin when theyquire treatment in hospitalized patients. required when blood glucose values are begin eating regular meals or are trans-In patients without a previous diagnosis 70 mg/dl (3.9 mmol/l), unless the event ferred to lower intensity care. Typically, aof diabetes, elevated blood glucose may is easily explained by other factors (such percentage (usually 75– 80%) of the totalbe due to “stress hyperglycemia,” a condi- as a missed meal, etc.). daily intravenous infusion dose is propor-tion that can be established by a review of Occasional patients with a prior his- tionately divided into basal and prandialprior records or measurement of an A1C. tory of successful tight glycemic control in components (see below). Importantly,A1C values 6.5% suggest that diabetes the outpatient setting who are clinically subcutaneous insulin must be given 1– 4preceded hospitalization (359). Hypogly- stable may be maintained with a glucose h prior to discontinuation of intravenouscemia has been defined as any blood glu- range below the above cut points. Con- insulin to prevent hyperglycemia (367).cose 70 mg/dl (3.9 mmol/l). This is the versely, higher glucose ranges may be ac- b. Subcutaneous insulin. Scheduledstandard definition in outpatients and ceptable in terminally ill patients or in subcutaneous insulin is the preferredcorrelates with the initial threshold for the patients with severe comorbidities, as method for achieving and maintainingrelease of counterregulatory hormones well as in those in patient-care settings glucose control in non-ICU patients with(177). Severe hypoglycemia in hospital- where frequent glucose monitoring or diabetes or stress hyperglycemia. The rec-ized patients has been defined by many close nursing supervision is not feasible. ommended components of inpatient sub-as 40 mg/dl (2.2 mmol/l), although Clinical judgment, combined with cutaneous insulin regimens include athis is lower than the 50 mg/dl (2.8 ongoing assessment of the patient’s clini- basal, nutritional, and supplemental (cor-mmol/l) level at which cognitive impair- cal status, including changes in the trajec- rection) component (345,346,368). Eachment begins in normal individuals tory of glucose measures, severity of component can be met by one of several(177,360,361). As with hyperglycemia, illness, nutritional status, or concurrent available insulin products, depending onhypoglycemia among inpatients is also as- use of medications that might affect glu- the particular hospital situation. Thesociated with adverse short- and long- cose levels (e.g., steroids, octreotide) reader is referred to several recent publi-term outcomes. Early recognition and must be incorporated into the day-to-day cations and reviews that describe cur-treatment of mild to moderate hypoglyce- decisions regarding insulin dosing (363). rently available insulin preparations andmia (40 and 69 mg/dl [2.2 and 3.8 mmol/ protocols (366 –370).l]) can prevent deterioration to a more 2. Treatment options in hospitalized A topic that deserves particular atten-severe episode with potential adverse se- patientsquelae (361,362). In the hospital setting, insulin therapy is tion is the persistent overuse of what hasi. Critically ill patients. Based on the the preferred method of glycemic control been branded as sliding scale insulin (SSI)weight of the available evidence, for the in majority of clinical situations (346). In for management of hyperglycemia. Themajority of critically ill patients in the ICU the ICU, intravenous infusion is the pre- term “correction insulin,” which refers tosetting, insulin infusion should be used to ferred route of insulin administration. the use of additional short or rapid-actingcontrol hyperglycemia, with a starting Outside of critical care units, subcutane- insulin with scheduled insulin doses tothreshold of 180 mg/dl (10.0 mmol/l). ous insulin is used much more frequently. treat blood glucose above desired targets,Once intravenous insulin is started, the Oral agents have a limited role in the in- is preferred (345). Prolonged therapyglucose level should be maintained be- patient setting. with SSI as the sole regimen is ineffectivetween 140 and 180 mg/dl (7.8 and 10.0 a. Intravenous insulin infusions. In the in the majority of patients (and potentiallymmol/l). Greater benefit may be realized critical care setting, continuous intrave- dangerous in type 1 diabetes) (370 –375).at the lower end of this range. Although nous insulin infusion has been shown to c. Noninsulin agents. These agents arestrong evidence is lacking, somewhat be the most effective method for achiev- inappropriate in the majority of hospital-lower glucose targets may be appropriate ing specific glycemic targets (346). Be- ized patients because they are less titrat-in selected patients. However, targets cause of the very short half-life of able than insulin in the short tem and are 110 mg/dl (6.1 mmol/l) are not recom- circulating insulin, intravenous delivery meant to be used in patients eating on amended. Use of insulin infusion protocols allows rapid dosing adjustments to ad- regular meal schedule. Continuation ofwith demonstrated safety and efficacy, re- dress alterations in patients’ status. these agents may be appropriate in se-sulting in low rates of hypoglycemia, are Intravenous insulin is ideally admin- lected stable patients who are expected tohighly recommended. istered via validated written or computer- consume meals at regular intervals. Spe-ii. Noncritically ill patients. With no pro- ized protocols that allow for predefined cific caution is required with metformin,spective, RCT data to inform specific gly- adjustments to the insulin infusion rate due to the possibility that a contraindica-cemic targets in noncritically ill patients, according to glycemic fluctuations and in- tion may develop during the hospitaliza-recommendations are based on clinical sulin dose. An extensive review of the tion, such as renal insufficiency, unstableexperience and judgment. For the major- merits and deficiencies of published pro- hemodynamic status, or need for an im-ity of noncritically ill patients treated with tocols is beyond the intent of this state- aging study that requires a radio-contrastinsulin, premeal glucose targets should ment, and the reader is referred to several dye (345,376). Injectable noninsulingenerally be 140 mg/dl (7.8 mmol/l) available reports and reviews (364 –366). therapies such as exenatide and pramlint-care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S45
    • Standards of Medical Careide have limitations similar to those of heart failure, renal or liver disease, malig- conducting self-management in the hos-oral agents in the hospital setting. nancy, infection, or sepsis (379,379,380). pital, it is imperative that basal, prandial,d. Specific clinical situations Additional triggering events leading to and correction doses of insulin and resultsi. Insulin pumps. Patients who use CSII iatrogenic hypoglycemia include sudden of bedside glucose monitoring be re-pump therapy in the outpatient setting reduction of corticosteroid dose, altered corded as part of the patient’s hospitalcan be candidates for diabetes self- ability of the patient to self-report symp- medical record. While many institutionsmanagement in the hospital, provided toms, reduction of oral intake, emesis, allow patients on insulin pumps to con-that they have the mental and physical new NPO status, inappropriate timing of tinue these devices in the hospital, otherscapacity to do so (346,368). It is impor- short- or rapid-acting insulin in relation express concern regarding use of a devicetant that nursing personnel document to meals, reduction of rate of administra- unfamiliar to staff, particularly in patientsbasal rates and bolus doses on a regular tion of intravenous dextrose, and unex- who are not able to manage their ownbasis (at least daily). The availability of pected interruption of enteral feedings or pump therapy. If a patient is too ill tohospital personnel with expertise in CSII parenteral nutrition. self-manage either multiple daily injec-therapy is essential. Despite the preventable nature of tions or CSII, then appropriate subcuta-ii. Enteral nutrition. Hyperglycemia is a many inpatient episodes of hypoglyce- neous doses can be calculated on the basiscommon side effect of inpatient enteral mia, institutions are more likely to have of their basal and bolus insulin needs dur-nutrition therapy (377). A recent report nursing protocols for the treatment of hy- ing hospitalization, with adjustments forusing a combination of basal insulin with poglycemia than for its prevention. changes in nutritional or metabolic status.correction insulin achieved a mean glu- Tracking such episodes and analyzingcose value of 160 mg/dl (8.9 mmol/l). their causes are important quality im- 5. DSME in the hospitalSimilar results were achieved in the group provement activities. Teaching diabetes self-management torandomized to receive SSI alone; how- patients in hospitals is a challenging task.ever, 48% of patients required the addi- 3. Diabetes care providers in the Patients are ill, under increased stress re-tion of intermediate-acting insulin to hospital lated to their hospitalization and diagno-achieve glycemic targets (373). Inpatient diabetes management may be sis, and in an environment not conduciveiii. Parenteral nutrition. The high glu- effectively provided by primary care phy- to learning. Ideally, people with diabetescose load in standard parenteral nutrition sicians, endocrinologists, or hospitalists. should be taught at a time and place con-frequently results in hyperglycemia, Involvement of appropriately trained spe- ducive to learning—as an outpatient inwhich is associated with a higher inci- cialists or specialty teams may reduce a recognized program of diabetesdence of complications and mortality in length of stay, improve glycemic control, education.critically ill ICU patients (378). Insulin and improve outcomes (381–384). In the For the hospitalized patient, diabetestherapy is highly recommended, with glu- care of diabetes, implementation of stan- “survival skills” education is generally acose targets as defined previously by se- dardized order sets for scheduled and cor- feasible approach. Patients and/or familyverity of illness. rection-dose insulin may reduce reliance members receive sufficient informationiv. Glucocorticoid therapy. Hyperglyce- on sliding-scale management. A team ap- and training to enable safe care at home.mia is a common complication of cortico- proach is needed to establish hospital Those newly diagnosed with diabetes orsteroid therapy (363). Several approaches pathways. To achieve glycemic targets who are new to insulin and/or blood glu-have been proposed for treatment of this associated with improved hospital out- cose monitoring need to be instructedcondition, but there are no published comes, hospitals will need multidisci- before discharge. Those patients hospital-protocols or studies that investigate the plinary support to develop protocols for ized because of a crisis related to diabetesefficacy of these approaches. A reasonable subcutaneous insulin therapy that effec- management or poor care at home needapproach is to institute glucose monitor- tively and safely achieve glycemic targets education to prevent subsequent episodesing for at least 48 h in all patients receiv- (385). of hospitalization. An assessment of theing high dose glucocorticoid therapy and need for a home health referral or referralinitiate insulin as appropriate. In patients 4. Self-management in the hospital to an outpatient diabetes education pro-who are already being treated for hyper- Self-management of diabetes in the hos- gram should be part of discharge plan-glycemia, early adjustment of insulin pital may be appropriate for competent ning for all patients.doses is recommended. Importantly, dur- adult patients who have a stable level ofing steroid tapers, insulin dosing should consciousness, have reasonably stable 6. MNT in the hospitalbe proactively adjusted to avoid daily insulin requirements, successfully Hospital diets continue to be ordered byhypoglycemia. conduct self-management of diabetes at calorie levels based on the “ADA diet.”v. Hypoglycemia prevention. Hypogly- home, have physical skills needed to suc- However, since 1994 the ADA has not en-cemia, especially in insulin-treated pa- cessfully self-administer insulin and per- dorsed any single meal plan or specifiedtients, is the leading limiting factor in the form SMBG, have adequate oral intake, percentages of macronutrients, and theglycemic management of type 1 and type and are proficient in carbohydrate count- term “ADA diet” should no longer be2 diabetes (174). In the hospital, multiple ing, use of multiple daily insulin injec- used. Current nutrition recommenda-additional risk factors for hypoglycemia tions, or insulin pump therapy and sick- tions advise individualization based onare present, even among patients who are day management. The patient and treatment goals, physiologic parameters,neither “brittle” nor tightly controlled. Pa- physician, in consultation with nursing and medication usage. Because of thetients with or without diabetes may expe- staff, must agree that patient self- complexity of nutrition issues in the hos-rience hypoglycemia in the hospital in management is appropriate under the pital, a registered dietitian, knowledge-association with altered nutritional state, conditions of hospitalization. For patients able and skilled in MNT, should serve asS46 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statementan inpatient team member. The dietitian limited by the lack of reliability in the hy- IX. STRATEGIES FORis responsible for integrating information poglycemic range as well as by cost. IMPROVING DIABETESabout the patient’s clinical condition, eat- CARE — The implementation of theing, and lifestyle habits and for establish- 8. Discharge planning standards of care for diabetes has beening treatment goals in order to determine It is important to anticipate the postdis- suboptimal in most clinical settings. A re-a realistic plan for nutrition therapy charge antihyperglycemic regimen in all cent report (393) indicated that only(386,387). patients with diabetes or newly discov- 57.1% of adults with diagnosed diabetes ered hyperglycemia. The optimal pro- achieved an A1C of 7%, only 45.5% gram will need to consider the type and had a blood pressure 130/80 mmHg,7. Bedside blood glucose monitoring severity of diabetes, the effects of the and just 46.5% had a total cholesterolBedside blood glucose monitoring using patient’s illness on blood glucose levels, 200 mg/dl. Most distressing was thatpoint-of-care glucose meters is performed and the capacities and desires of the pa- only 12.2% of people with diabetesbefore meals and bedtime in the majority tient. Smooth transition to outpatient achieved all three treatment goals.of inpatients who are eating usual meals. care should be ensured, especially in While numerous interventions to im-In patients who are receiving continuous those new to insulin therapy or in prove adherence to the recommendedenteral or parenteral nutrition, glucose whom the diabetes regimen has been standards have been implemented, themonitoring is optimally performed every substantially altered during the hospi- challenge of providing uniformly effective4 – 6 h. In patients who are receiving cy- talization. All patients in whom the di- diabetes care has thus far defied a simplecled enteral or parenteral nutrition, the agnosis of diabetes is new should have, solution. A major contributor to subopti-schedule for glucose monitoring can be at minimum, “survival skills” training mal care is a delivery system that too oftenindividualized but should be frequent prior to discharge. is fragmented, lacks clinical informationenough to detect hyperglycemia during It is recommended that the following capabilities, often duplicates services, andfeedings and risk of hypoglycemia when areas be reviewed and addressed prior to is poorly designed for the delivery offeedings are interrupted (374,376). More hospital discharge: chronic care. The chronic care modelfrequent blood glucose testing ranging from (CCM) includes five core elements for theevery 30 min to every 2 h is required for ● level of understanding related to the di- provision of optimal care of patients withpatients on intravenous insulin infusions. agnosis of diabetes chronic disease: delivery system design, Safe and rational glycemic manage- ● SMBG and explanation of home blood self-management support, decision sup-ment relies on the accuracy of blood glu- glucose goals port, clinical information systems, andcose measurements using point-of-care ● definition, recognition, treatment, and community resources and policies. Redef-blood glucose meters, which have several prevention of hyperglycemia and inition of the roles of the clinic staff andimportant limitations. Although the FDA hypoglycemia promoting self-management on the partallows a 20% error for glucose meters, ● identification of health care provider of the patient are fundamental to the suc-questions about the appropriateness of who will provide diabetes care after cessful implementation of the CCMthis criterion have been raised (388). Glu- discharge (394). Collaborative, multidisciplinarycose measures differ significantly between ● information on consistent eating teams are best suited to provide such careplasma and whole blood, terms which are patterns for people with chronic conditions likeoften used interchangeably and can lead ● when and how to take blood glucose– diabetes and to empower patients’ perfor-to misinterpretation. Most commercially lowering medications including insulin mance of appropriate self-management.available capillary glucose meters intro- administration (if going home on Alterations in reimbursement that rewardduce a correction factor of 1.12 to re- insulin) the provision of quality care, as defined byport a “plasma-adjusted” value (389). ● sick-day management the attainment of quality measures devel- Significant discrepancies between ● proper use and disposal of needles and oped by such programs as the ADA/capillary, venous, and arterial plasma syringes National Committee for Qualitysamples have been observed in patients Assurance Diabetes Provider Recognitionwith low or high hemoglobin concentra- More expanded diabetes education can Program, will also be required to achievetions, hypoperfusion, and the presence of be arranged in the community. An out- desired outcome goals.interfering substances (389,390). Analyt- patient follow-up visit with the primary In recent years, numerous health careical variability has been described with care provider, endocrinologist, or diabe- organizations, ranging from large healthseveral point-of-care meters (391). Any tes educator within 1 month of discharge care systems such as the U.S. Veteran’sglucose result that does not correlate with is advised for all patients having hypergly- Administration to small private practices,the patient’s status should be confirmed cemia in the hospital. Clear communica- have implemented strategies to improvethrough conventional laboratory sam- tion with outpatient providers either diabetes care. Successful programs havepling of PG. directly or via hospital discharge summa- published results showing improvement While laboratory measurement of PG ries facilitates safe transitions to outpa- in process measures such as measurementhas less variability and interference, mul- tient care. Providing information of A1C, lipids, and blood pressure. Effectstiple daily phlebotomies are not practical. regarding the cause or the plan for deter- on in important intermediate outcomes,The use of indwelling lines as the sam- mining the cause of hyperglycemia, re- such as mean A1C for populations, havepling source also poses risks for infection. lated complications and comorbidities, been more difficult to demonstrate (395–Studies performed using continuous in- and recommended treatments can assist 397), although examples do exist (398 –terstitial glucose monitoring systems in outpatient providers as they assume on- 402), often taking more than 1 year tothe critical care setting (392) currently are going care. manifest (394). Features of successfulcare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S47
    • Standards of Medical Careprograms reported in the literature tion. When practices are compared, those betes Association and 1999 Worldinclude that address more of the CCM elements Health Organization criteria for hyper- demonstrate lower A1C levels and lower glycemia in the diagnosis and prediction● Delivery of DSME: increases adherence cardiovascular risk scores (408). The of diabetes. Diabetes Care 2000;23: 1108 –1112 to standard of care and educating pa- most successful practices have an institu- 11. Knowler WC, Barrett-Connor E, Fowler tients on glycemic targets and improves tional priority for quality of care, involve SE, Hamman RF, Lachin JM, Walker EA, the percentage of patients who reach all of the staff in their initiatives, redesign Nathan DM, Diabetes Prevention Pro- goal A1C (142,403) their delivery system, activate and edu- gram Research Group. Reduction in the● Adoption of practice guidelines, with cate their patients, and use electronic incidence of type 2 diabetes with lifestyle participation of health care profession- health record tools (409,410). intervention or metformin. N Engl J Med als in the process of development: NDEP maintains an online resource 2002;346:393– 403 Guidelines should be readily accessible (www.betterdiabetescare.nih.gov) to help 12. Tuomilehto J, Lindstrom J, Eriksson JG, ¨ at the point of service, preferably as health care professionals design and im- Valle TT, Hamalainen H, Ilanne-Parikka ¨ ¨ ¨ computerized reminders at the point of plement more effective health care deliv- P, Keinanen-Kiukaanniemi S, Laakso M, ¨ care. Guidelines should begin with a ery systems for those with diabetes. Louheranta A, Rastas M, Salminen V, Uusitupa M, Finnish Diabetes Preven- summary of their major recommenda- It is clear that optimal diabetes man- tion Study Group. Prevention of type 2 tions instructing health care profes- agement requires an organized, system- diabetes mellitus by changes in lifestyle sionals what to do and how to do it. atic approach and involvement of a among subjects with impaired glucose● Use of checklists that mirror guidelines: coordinated team of dedicated health care tolerance. N Engl J Med 2001;344: successful at improving adherence to professionals working in an environment 1343–1350 standards of care where quality care is a priority. 13. Pan XR, Li GW, Hu YH, Wang JX, Yang● Systems changes: such as provision of WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao automated reminders to health care HB, Liu PA, Jiang XG, Jiang YY, Wang JP, professionals and patients and audit References Zheng H, Zhang H, Bennett PH, Howard and feedback of process and outcome 1. American Diabetes Asociation. Medical BV. Effects of diet and exercise in pre- Management of Type 1 Diabetes. Alexan- venting NIDDM in people with impaired data to providers glucose tolerance. The Da Qing IGT and● dria, VA, American Diabetes Associa- Quality improvement programs com- tion, 2008 Diabetes Study. Diabetes Care 1997;20: bining continuous quality improve- 2. American Diabetes Asociation. Medical 537–544 ment or other cycles of analysis and Management of Type 2 Diabetes. Alexan- 14. Buchanan TA, Xiang AH, Peters RK, Kjos intervention with provider perfor- dria, VA, American Diabetes Associa- SL, Marroquin A, Goico J, Ochoa C, Tan mance data tion, 2008 S, Berkowitz K, Hodis HN, Azen SP.● Practice changes: such as availability of 3. American Diabetes Association. Intensive Preservation of pancreatic beta-cell point of care testing of A1C, scheduling Diabetes Management. Alexandria, VA, function and prevention of type 2 diabe- planned diabetes visits, clustering of American Diabetes Association, 2009 tes by pharmacological treatment of in- dedicated diabetes visits into specific 4. Expert Committee on the Diagnosis and sulin resistance in high-risk hispanic Classification of Diabetes Mellitus. Re- women. Diabetes 2002;51:2796 –2803 times within a primary care practice port of the Expert Committee on the Di- 15. Chiasson JL, Josse RG, Gomis R, schedule, or group visits and/or visits agnosis and Classification of Diabetes Hanefeld M, Karasik A, Laakso M, with multiple health care professionals Mellitus. Diabetes Care 1997;20:1183– STOP-NIDDM Trail Research Group. on a single day 1197 Acarbose for prevention of type 2 diabe-● Tracking systems with either an elec- 5. International Expert Committee. Inter- tes mellitus: the STOP-NIDDM random- tronic medical record or patient regis- national Expert Committee report on the ised trial. Lancet 2002;359:2072–2077 try: helpful at increasing adherence to role of the A1C assay in the diagnosis of 16. DREAM (Diabetes REduction Assess- standards of care by prospectively iden- diabetes. Diabetes Care 2009;32:1327– ment with ramipril and rosiglitazone tifying those requiring assessments 1334 Medication) Trial Investigators, Gerstein and/or treatment modifications. They 6. American Diabetes Association. Diagno- HC, Yusuf S, Bosch J, Pogue J, Sheridan likely could have greater efficacy if they sis and classification of diabetes mellitus. P, Dinccag N, Hanefeld M, Hoogwerf B, Diabetes Care 2010;33(Suppl. 1):S62– Laakso M, Mohan V, Shaw J, Zinman B, suggested specific therapeutic interven- S69 Holman RR. Effect of rosiglitazone on tions to be considered for a particular 7. Genuth S, Alberti KG, Bennett P, Buse J, the frequency of diabetes in patients patient at a particular point in time Defronzo R, Kahn R, Kitzmiller J, with impaired glucose tolerance or im- (404). Knowler WC, Lebovitz H, Lernmark A, paired fasting glucose: a randomised● Availability of case or (preferably) care Nathan D, Palmer J, Rizza R, Saudek C, controlled trial. Lancet 2006;368:1096 – management services (405): Nurses, Shaw J, Steffes M, Stern M, Tuomilehto J, 1105 pharmacists, and other nonphysician Zimmet P, Expert Committee on the Di- 17. Ramachandran A, Snehalatha C, Mary S, health care professionals using detailed agnosis and Classification of Diabetes Mukesh B, Bhaskar AD, Vijay V, Indian algorithms working under the supervi- Mellitus. Follow-up report on the diag- Diabetes Prevention Programme (IDPP). sion of physicians have demonstrated nosis of diabetes mellitus. Diabetes Care The Indian Diabetes Prevention Pro- 2003;26:3160 –3167 gramme shows that lifestyle modifica- the greatest reduction in A1C and 9. Engelgau MM, Narayan KM, Herman tion and metformin prevent type 2 blood pressure (406,407). WH. Screening for type 2 diabetes. Dia- diabetes in Asian Indian subjects with betes Care 2000;23:1563–1580 impaired glucose tolerance (IDPP-1).Evidence suggests that these individual 10. Gabir MM, Hanson RL, Dabelea D, Im- Diabetologia 2006;49:289 –297initiatives work best when provided as peratore G, Roumain J, Bennett PH, 18. Johnson SL, Tabaei BP, Herman WH.components of a multifactorial interven- Knowler WC. The 1997 American Dia- The efficacy and cost of alternative strat-S48 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement egies for systematic screening for type 2 28. Kim C, Newton KM, Knopp RH. Gesta- 38. American Diabetes Association: Self- diabetes in the U.S. population 45–74 tional diabetes and the incidence of type monitoring of blood glucose. Diabetes years of age. Diabetes Care 2005;28: 2 diabetes: a systematic review. Diabetes Care 1994;17:81– 86 307–311 Care 2002;25:1862–1868 39. Welschen LM, Bloemendal E, Nijpels G, 19. Harris R, Donahue K, Rathore SS, Frame 29. Lindstrom J, Ilanne-Parikka P, Peltonen ¨ Dekker JM, Heine RJ, Stalman WA, P, Woolf SH, Lohr KN. Screening adults M, Aunola S, Eriksson JG, Hemio K, Ha- ¨ ¨ Bouter LM. Self-monitoring of blood for type 2 diabetes: a review of the evi- malainen H, Harkonen P, Keinanen- ¨ ¨ ¨ ¨ ¨ glucose in patients with type 2 diabetes dence for the U.S. Preventive Services Kiukaanniemi S, Laakso M, Louheranta who are not using insulin: a systematic Task Force. Ann Intern Med 2003;138: A, Mannelin M, Paturi M, Sundvall J, review. Diabetes Care 2005;28:1510 – 215–229 Valle TT, Uusitupa M, Tuomilehto J, 1517 20. U.S. Preventive Services Task Force. S. Finnish Diabetes Prevention Study 40. Farmer A, Wade A, Goyder E, Yudkin Preventive Services Task Force. S. Pre- Group. Sustained reduction in the inci- P, French D, Craven A, Holman R, ventive Services Task Force: Screening dence of type 2 diabetes by lifestyle in- Kinmonth AL, Neil A. Impact of self for type 2 diabetes mellitus in adults: tervention: follow-up of the Finnish monitoring of blood glucose in the man- recommendations and rationale. Ann Diabetes Prevention Study. Lancet 2006; agement of patients with non-insulin Intern Med 2003;138:212–214 368:1673–1679 treated diabetes: open parallel group 21. Writing Group for the SEARCH for Dia- 30. Li G, Zhang P, Wang J, Gregg EW, Yang randomised trial. BMJ 2007;335:132 betes in Youth Study Group, Dabelea D, W, Gong Q, Li H, Li H, Jiang Y, An Y, 41. O’Kane MJ, Bunting B, Copeland M, Bell RA, D’Agostino RB Jr, Imperatore G, Shuai Y, Zhang B, Zhang J, Thompson Coates VE, ESMON study group. Effi- Johansen JM, Linder B, Liu LL, Loots B, TJ, Gerzoff RB, Roglic G, Hu Y, Bennett cacy of self monitoring of blood glucose Marcovina S, Mayer-Davis EJ, Pettitt DJ, PH. The long-term effect of lifestyle in- in patients with newly diagnosed type 2 Waitzfelder B. Incidence of diabetes in terventions to prevent diabetes in the diabetes (ESMON study): randomised youth in the United States. JAMA 2007; China Da Qing Diabetes Prevention controlled trial. BMJ 2008;336:1174 – 297:2716 –2724 Study: a 20-year follow-up study. Lancet 1177 22. SEARCH for Diabetes in Youth Study 2008;371:1783–1789 42. Simon J, Gray A, Clarke P, Wade A, Neil Group, Liese AD, D’Agostino RB Jr, 31. Kosaka K, Noda M, Kuzuya T. Preven- A, Farmer A, Diabetes Glycaemic Educa- Hamman RF, Kilgo PD, Lawrence JM, tion of type 2 diabetes by lifestyle inter- tion and Monitoring Trial Group. Cost Liu LL, Loots B, Linder B, Marcovina S, vention: a Japanese trial in IGT males. effectiveness of self monitoring of blood Rodriguez B, Standiford D, Williams DE. Diabetes Res Clin Pract 2005;67:152– glucose in patients with non-insulin The burden of diabetes mellitus among 162 treated type 2 diabetes: economic evalu- US youth: prevalence estimates from the 32. Torgerson JS, Hauptman J, Boldrin MN, ation of data from the DiGEM trial. BMJ SEARCH for Diabetes in Youth Study. Sjostrom L. XENical in the prevention of ¨ ¨ 2008;336:1177–1180 Pediatrics 2006;118:1510 –1518 diabetes in obese subjects (XENDOS) 43. Sacks DB, Bruns DE, Goldstein DE, Ma- 23. American Diabetes Association: Type 2 study: a randomized study of orlistat as claren NK, McDonald JM, Parrott M. diabetes in children and adolescents an adjunct to lifestyle changes for the Guidelines and recommendations for (Consensus Statement). Diabetes Care prevention of type 2 diabetes in obese laboratory analysis in the diagnosis and 2000;23:381–389 patients. Diabetes Care 2004;27:155– management of diabetes mellitus. Clin 24. Lawrence JM, Contreras R, Chen W, 161 Chem 2002;48:436 – 472 Sacks DA. Trends in the prevalence of 33. Kawamori R, Tajima N, Iwamoto Y, 44. Juvenile Diabetes Research Foundation preexisting diabetes and gestational dia- Kashiwagi A, Shimamoto K, Kaku K, Continuous Glucose Monitoring Study betes mellitus among a racially/ethni- Voglibose Ph-3 Study Group. Voglib- Group, Tamborlane WV, Beck RW, cally diverse population of pregnant ose for prevention of type 2 diabetes Bode BW, Buckingham B, Chase HP, women, 1999 –2005. Diabetes Care mellitus: a randomised, double-blind Clemons R, Fiallo-Scharer R, Fox LA, 2008;31:899 –904 trial in Japanese individuals with im- Gilliam LK, Hirsch IB, Huang ES, Koll- 25. American Diabetes Association: Gesta- paired glucose tolerance. Lancet 2009; man C, Kowalski AJ, Laffel L, Lawrence tional diabetes mellitus (Position State- 373:1607–1614 JM, Lee J, Mauras N, O’Grady M, Ruedy ment). Diabetes Care 2004;27(Suppl. 34. DeFronzo RA, for ACT NOW Study KJ, Tansey M, Tsalikian E, Weinzimer S, 1):S88 –S90 Group. ACTos NOW Study for the Pre- Wilson DM, Wolpert H, Wysocki T, 26. HAPO Study Cooperative Research vention of Diabetes (ACT NOW) Study. Xing D: Continuous glucose monitoring Group, Metzger BE, Lowe LP, Dyer AR, Late-breaking abstract presented at 68th and intensive treatment of type 1 diabe- Trimble ER, Chaovarindr U, Coustan Annual Scientific Sessions of the Ameri- tes. N Engl J Med 2008; 359:1464 –1476 DR, Hadden DR, McCance DR, Hod M, can Diabetes Association, 6 June 2008, 45. Juvenile Diabetes Research Foundation McIntyre HD, Oats JJ, Persson B, Rogers San Francisco, CA Continuous Glucose Monitoring Study MS, Sacks DA. Hyperglycemia and ad- 35. Gerstein HC. Point: If it is important to Group: The effect of continuous glucose verse pregnancy outcomes. N Engl J Med prevent type 2 diabetes, it is important to monitoring in well-controlled type 1 di- 2008;358:1991–2002 consider all proven therapies within a abetes. Diabetes Care 2009;32:1378 – 27. Landon MB, Spong CY, Thom E, Car- comprehensive approach. Diabetes Care 1383 penter MW, Ramin SM, Casey B, Wap- 2007;30:432– 434 46. Stratton IM, Adler AI, Neil HA, Mat- ner RJ, Varner MW, Rouse DJ, Thorp JM 36. Nathan DM, Davidson MB, DeFronzo thews DR, Manley SE, Cull CA, Hadden Jr, Sciscione A, Catalano P, Harper M, RA, Heine RJ, Henry RR, Pratley R, Zin- D, Turner RC, Holman RR. Association Saade G, Lain KY, Sorokin Y, Peaceman man B, American Diabetes Association. of glycaemia with macrovascular and AM, Tolosa JE, Anderson GB, Eunice Impaired fasting glucose and impaired microvascular complications of type 2 Kennedy Shriver National Institute of glucose tolerance: implications for care. diabetes (UKPDS 35): prospective ob- Child Health and Human Development Diabetes Care 2007;30:753–759 servational study. BMJ 2000;321:405– Maternal-Fetal Medicine Units Network. 37. American Diabetes Association: Consen- 412 A multicenter, randomized trial of treat- sus statement on self-monitoring of 47. Cagliero E, Levina EV, Nathan DM. Im- ment for mild gestational diabetes. blood glucose. Diabetes Care 1987;10: mediate feedback of HbA1c levels im- N Engl J Med 2009;361:1339 –1348 95–99 proves glycemic control in type 1 andcare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S49
    • Standards of Medical Care insulin-treated type 2 diabetic patients. betic microvascular complications in of Diabetes Interventions and Complica- Diabetes Care 1999;22:1785–1789 Japanese patients with non-insulin-de- tions (DCCT/EDIC) Study Research 48. Miller CD, Barnes CS, Phillips LS, Zi- pendent diabetes mellitus: a randomized Group. Intensive diabetes treatment and emer DC, Gallina DL, Cook CB, Mary- prospective 6-year study. Diabetes Res cardiovascular disease in patients with man SD, El-Kebbi IM. Rapid A1c Clin Pract 1995;28:103–117 type 1 diabetes. N Engl J Med 2005;353: availability improves clinical decision- 57. Effect of intensive blood-glucose control 2643–2653 making in an urban primary care clinic. with metformin on complications in 67. Diabetes Control and Complications Diabetes Care 2003;26:1158 –1163 overweight patients with type 2 diabetes Trial/Epidemiology of Diabetes Inter- 49. Nathan DM, Kuenen J, Borg R, Zheng H, (UKPDS 34): UK Prospective Diabetes ventions and Complications (DCCT/ Schoenfeld D, Heine RJ, A1c-Derived Study (UKPDS) Group. Lancet 1998; EDIC) Research Group, Nathan DM, Average Glucose Study Group. Translat- 352:854 – 865 Zinman B, Cleary PA, Backlund JY, Ge- ing the A1C assay into estimated average 58. Intensive blood-glucose control with nuth S, Miller R, Orchard TJ. Modern- glucose values. Diabetes Care 2008;31: sulphonylureas or insulin compared day clinical course of type 1 diabetes 1473–1478 with conventional treatment and risk of mellitus after 30 years’ duration: the di- 50. Rohlfing CL, Wiedmeyer HM, Little RR, complications in patients with type 2 di- abetes control and complications trial/ England JD, Tennill A, Goldstein DE. abetes (UKPDS 33): UK Prospective Di- epidemiology of diabetes interventions Defining the relationship between abetes Study (UKPDS) Group. Lancet and complications and Pittsburgh epide- plasma glucose and HbA(1c): analysis of 1998;352:837– 853 miology of diabetes complications expe- glucose profiles and HbA(1c) in the Di- 59. Holman RR, Paul SK, Bethel MA, Mat- rience (1983–2005). Arch Intern Med abetes Control and Complications Trial. thews DR, Neil HA: 10-Year follow-up of 2009;169:1307–1316 Diabetes Care 2002;25:275–278 intensive glucose control in type 2 dia- 68. Action to Control Cardiovascular Risk in 51. Diabetes Research in Children Network betes. N Engl J Med 2008;359:1577– Diabetes Study Group, Gerstein HC, (DirecNet) Study Group, Wilson DM, 1589 Miller ME, Byington RP, Goff DC Jr, Big- Kollman. Relationship of A1C to glucose 60. Duckworth W, Abraira C, Moritz T, ger JT, Buse JB, Cushman WC, Genuth concentrations in children with type 1 Reda D, Emanuele N, Reaven PD, Zieve S, Ismail-Beigi F, Grimm RH Jr, Probst- diabetes: assessments by high-frequency FJ, Marks J, Davis SN, Hayward R, War- field JL, Simons-Morton DG, Friedewald glucose determinations by sensors. Dia- ren SR, Goldman S, McCarren M, Vitek WT. Effects of intensive glucose lower- betes Care 2008;31:381–385 ME, Henderson WG, Huang GD, VADT ing in type 2 diabetes. N Engl J Med 52. Skyler JS, Bergenstal R, Bonow RO, Buse Investigators. Glucose control and vas- 2008;358:2545–2559 J, Deedwania P, Gale EA, Howard BV, cular complications in veterans with 69. Duckworth W. VADT Results. Late- Kirkman MS, Kosiborod M, Reaven P, type 2 diabetes. N Engl J Med 2009;360: breaking abstract presented at 68th An- Sherwin RS, American Diabetes Associ- 129 –139 nual Scientific Sessions of the American ation, American College of Cardiology 61. Moritz T, Duckworth W, Abraira C. Vet- Diabetes Association, 6 June 2008, San Foundation, American Heart Associa- erans Affairs diabetes trial– corrections. Francisco, CA tion. Intensive glycemic control and the N Engl J Med 2009;361:1024 –1025 70. Reaven PD, Moritz TE, Schwenke DC, prevention of cardiovascular events: im- 62. Lawson ML, Gerstein HC, Tsui E, Zin- Anderson RJ, Criqui M, Detrano R, plications of the ACCORD, ADVANCE, man B. Effect of intensive therapy on Emanuele N, Kayshap M, Marks J, Mu- and VA diabetes trials: a position state- early macrovascular disease in young in- daliar S, Rao RH, Shah JH, Goldman S, ment of the American Diabetes Associa- dividuals with type 1 diabetes: A system- Reda DJ, McCarren M, Abraira C, Duck- tion and a scientific statement of the atic review and meta-analysis. Diabetes worth W: Intensive glucose lowering American College of Cardiology Foun- Care 1999;22(Suppl. 2):B35–B39 therapy reduces cardiovascular disease dation and the American Heart Associa- 63. ADVANCE Collaborative Group, Patel events in VADT participants with lower tion. Diabetes Care 2009;32:187–192 A, MacMahon S, Chalmers J, Neal B, Bil- calcified coronary atherosclerosis. Dia- 53. The effect of intensive treatment of dia- lot L, Woodward M, Marre M, Cooper betes 2009;59:2642–2648 betes on the development and progres- M, Glasziou P, Grobbee D, Hamet P, 71. Turnbull FM, Abraira C, Anderson RJ, sion of long-term complications in Harrap S, Heller S, Liu L, Mancia G, Mo- Byington RP, Chalmers JP, Duckworth insulin-dependent diabetes mellitus. gensen CE, Pan C, Poulter N, Rodgers A, WC, Evans GW, Gerstein HC, Holman The Diabetes Control and Complica- Williams B, Bompoint S, de Galan BE, RR, Moritz TE, Neal BC, Ninomiya T, tions Trial Research Group. N Engl Joshi R, Travert F. Intensive blood glu- Patel AA, Paul SK, Travert F, Woodward J Med 1993;329:977–986 cose control and vascular outcomes in M: Intensive glucose control and macro- 54. Retinopathy and nephropathy in pa- patients with type 2 diabetes. N Engl vascular outcomes in type 2 diabetes. tients with type 1 diabetes four years af- J Med 2008;358:2560 –2572 Diabetologia 2009;52:2288 –2298 ter a trial of intensive therapy. The 64. Selvin E, Marinopoulos S, Berkenblit G, 72. American Diabetes Association: Post- Diabetes Control and Complications Rami T, Brancati FL, Powe NR, Golden prandial blood glucose (Consensus Trial/Epidemiology of Diabetes Interven- SH. Meta-analysis: glycosylated hemo- Statement). Diabetes Care 2001;24:775– tions and Complications Research Group. globin and cardiovascular disease in di- 778 N Engl J Med 2000;342:381–389 abetes mellitus. Ann Intern Med 2004; 73. Ceriello A, Taboga C, Tonutti L, Quagli- 55. Martin CL, Albers J, Herman WH, 141:421– 431 aro L, Piconi L, Bais B, Da Ros R, Motz E. Cleary P, Waberski B, Greene DA, 65. Stettler C, Allemann S, Juni P, Cull CA, ¨ Evidence for an independent and cu- Stevens MJ, Feldman EL, DCCT/EDIC Holman RR, Egger M, Krahenbuhl S, ¨ ¨ mulative effect of postprandial hyper- Research Group. Neuropathy among the Diem P. Glycemic control and macro- triglyceridemia and hyperglycemia on diabetes control and complications trial vascular disease in types 1 and 2 diabetes endothelial dysfunction and oxidative cohort 8 years after trial completion. Di- mellitus: Meta-analysis of randomized stress generation: effects of short- and abetes Care 2006;29:340 –344 trials. Am Heart J 2006;152:27–38 long-term simvastatin treatment. Circu- 56. Ohkubo Y, Kishikawa H, Araki E, Miyata 66. Nathan DM, Cleary PA, Backlund JY, lation 2002;106:1211–1218 T, Isami S, Motoyoshi S, Kojima Y, Fu- Genuth SM, Lachin JM, Orchard TJ, 74. Raz I, Wilson PW, Strojek K, Kowalska I, ruyoshi N, Shichiri M. Intensive insulin Raskin P, Zinman B, Diabetes Control Bozikov V, Gitt AK, Jermendy G, Cam- therapy prevents the progression of dia- and Complications Trial/Epidemiology paigne BN, Kerr L, Milicevic Z, JacoberS50 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement SJ. Effects of prandial versus fasting gly- ble, intensive insulin management to en- terns on blood pressure. DASH Collab- cemia on cardiovascular outcomes in able dietary freedom in people with type orative Research Group. N Engl J Med type 2 diabetes: the HEART2D trial. Di- 1 diabetes: dose adjustment for normal 1997;336:1117–1124 abetes Care 2009;32:381–386 eating (DAFNE) randomised controlled 94. Norris SL, Zhang X, Avenell A, Gregg E, 75. Metzger BE, Buchanan TA, Coustan DR, trial. BMJ 2002;325:746 Bowman B, Schmid CH, Lau J. Long- de Leiva A, Dunger DB, Hadden DR, 84. Franz MJ, Monk A, Barry B, McClain K, term effectiveness of weight-loss inter- Hod M, Kitzmiller JL, Kjos SL, Oats JN, Weaver T, Cooper N, Upham P, Bergen- ventions in adults with pre-diabetes: a Pettitt DJ, Sacks DA, Zoupas C. Sum- stal R, Mazze RS. Effectiveness of medi- review. Am J Prev Med 2005;28:126 – mary and recommendations of the Fifth cal nutrition therapy provided by 139 International Workshop-Conference on dietitians in the management of non-in- 95. Klein S, Sheard NF, Pi-Sunyer X, Daly A, Gestational Diabetes Mellitus. Diabetes sulin-dependent diabetes mellitus: a Wylie-Rosett J, Kulkarni K, Clark NG, Care 2007;30(Suppl. 2):S251–S260 randomized, controlled clinical trial. American Diabetes Association, North 76. Kitzmiller JL, Block JM, Brown FM, J Am Diet Assoc 1995;95:1009 –1017 American Association for the Study of Catalano PM, Conway DL, Coustan DR, 85. Goldhaber-Fiebert JD, Goldhaber-Fiebert Obesity, American Society for Clinical Gunderson EP, Herman WH, Hoffman SN, Tristan ML, Nathan DM. Randomized ´ Nutrition. Weight management through LD, Inturrisi M, Jovanovic LB, Kjos SI, controlled community-based nutrition lifestyle modification for the prevention Knopp RH, Montoro MN, Ogata ES, and exercise intervention improves glyce- and management of type 2 diabetes: ra- Paramsothy P, Reader DM, Rosenn BM, mia and cardiovascular risk factors in type tionale and strategies: a statement of Thomas AM, Kirkman MS. Managing 2 diabetic patients in rural Costa Rica. Di- the American Diabetes Association, the preexisting diabetes for pregnancy: sum- abetes Care 2003;26:24 –29 North American Association for the mary of evidence and consensus recom- 86. Lemon CC, Lacey K, Lohse B, Hubacher Study of Obesity, and the American So- mendations for care. Diabetes Care DO, Klawitter B, Palta M. Outcomes ciety for Clinical Nutrition. Diabetes 2008;31:1060 –1079 monitoring of health, behavior, and Care 2004;27:2067–2073 77. DeWitt DE, Hirsch IB. Outpatient insu- quality of life after nutrition intervention 96. Norris SL, Zhang X, Avenell A, Gregg E, lin therapy in type 1 and type 2 diabetes in adults with type 2 diabetes. J Am Diet Schmid CH, Kim C, Lau J. Efficacy of mellitus: scientific review. JAMA 2003; Assoc 2004;104:1805–1815 pharmacotherapy for weight loss in 289:2254 –2264 87. Miller CK, Edwards L, Kissling G, San- adults with type 2 diabetes mellitus: a 78. Rosenstock J, Dailey G, Massi-Benedetti ville L. Nutrition education improves meta-analysis. Arch Intern Med 2004; M, Fritsche A, Lin Z, Salzman A. Re- metabolic outcomes among older adults 164:1395–1404 duced hypoglycemia risk with insulin with diabetes mellitus: results from a 97. Wolf AM, Conaway MR, Crowther JQ, glargine: a meta-analysis comparing in- randomized controlled trial. Prev Med Hazen KY, L Nadler J, Oneida B, Bovb- sulin glargine with human NPH insulin 2002;34:252–259 jerg VE, Improving Control with Activity in type 2 diabetes. Diabetes Care 2005; 88. Wilson C, Brown T, Acton K, Gilliland S. and Nutrition (ICAN) Study. Translat- 28:950 –955 Effects of clinical nutrition education ing lifestyle intervention to practice in 79. Mooradian AD, Bernbaum M, Albert SG. and educator discipline on glycemic obese patients with type 2 diabetes: Im- Narrative review: a rational approach to control outcomes in the Indian health proving Control with Activity and Nutri- starting insulin therapy. Ann Intern Med service. Diabetes Care 2003;26:2500 – tion (ICAN) study. Diabetes Care 2004; 2006;145:125–134 2504 27:1570 –1576 80. Nathan DM, Buse JB, Davidson MB, 89. Graber AL, Elasy TA, Quinn D, Wolff K, 98. Manning RM, Jung RT, Leese GP, New- Heine RJ, Holman RR, Sherwin R, Zin- Brown A. Improving glycemic control in ton RW. The comparison of four weight man B. Management of hyperglycemia in adults with diabetes mellitus: shared re- reduction strategies aimed at overweight type 2 diabetes: a consensus algorithm sponsibility in primary care practices. patients with diabetes mellitus: four- for the initiation and adjustment of ther- South Med J 2002;95:684 – 690 yearfollow-up.DiabetMed1998;15:497– apy: a consensus statement from the 90. Gaetke LM, Stuart MA, Truszczynska H. 502 American Diabetes Association and the A single nutrition counseling session 99. Shai I, Schwarzfuchs D, Henkin Y, Sha- European Association for the Study of with a registered dietitian improves har DR, Witkow S, Greenberg I, Golan Diabetes. Diabetes Care 2006;29:1963– short-term clinical outcomes for rural R, Fraser D, Bolotin A, Vardi H, Tangi- 1972 Kentucky patients with chronic diseases. Rozental O, Zuk-Ramot R, Sarusi B, 81. Nathan DM, Buse JB, Davidson MB, Fer- J Am Diet Assoc 2006;106:109 –112 Brickner D, Schwartz Z, Sheiner E, rannini E, Holman RR, Sherwin R, Zin- 91. Yu-Poth S, Zhao G, Etherton T, Naglak Marko R, Katorza E, Thiery J, Fiedler man B, American Diabetes Association, M, Jonnalagadda S, Kris-Etherton PM. GM, Bluher M, Stumvoll M, Stampfer ¨ European Association for Study of Dia- Effects of the National Cholesterol Ed- MJ, Dietary Intervention Randomized betes. Medical management of hypergly- ucation Program’s Step I and Step II Controlled Trial (DIRECT) Group. cemia in type 2 diabetes: a consensus dietary intervention programs on car- Weight loss with a low-carbohydrate, algorithm for the initiation and adjust- diovascular disease risk factors: a meta- Mediterranean, or low-fat diet. N Engl ment of therapy: a consensus statement analysis. Am J Clin Nutr 1999;69:632– J Med 2008;359:229 –241 of the American Diabetes Association 646 100. Franz MJ, VanWormer JJ, Crain AL, and the European Association for the 92. Van Horn L, McCoin M, Kris-Etherton Boucher JL, Histon T, Caplan W, Bow- Study of Diabetes. Diabetes Care 2009; PM, Burke F, Carson JA, Champagne man JD, Pronk NP. Weight-loss out- 32:193–203 CM, Karmally W, Sikand G. The evi- comes: a systematic review and meta- 82. Bantle JP, Wylie-Rosett J, Albright AL, dence for dietary prevention and treat- analysis of weight-loss clinical trials with Apovian CM, Clark NG, Franz MJ, ment of cardiovascular disease. J Am a minimum 1-year follow-up. J Am Diet Hoogwerf BJ, Lichtenstein AH, Mayer- Diet Assoc 2008;108:287–331 Assoc 2007;107:1755–1767 Davis E, Mooradian AD, Wheeler ML. 93. Appel LJ, Moore TJ, Obarzanek E, 101. Look AHEAD Research Group, Pi-Su- Nutrition recommendations and inter- Vollmer WM, Svetkey LP, Sacks FM, nyer X, Blackburn G, Brancati FL, Bray ventions for diabetes—2006. Diabetes Bray GA, Vogt TM, Cutler JA, GA, Bright R, Clark JM, Curtis JM, Es- Care 2006;29:2140 –2157 Windhauser MM, Lin PH, Karanja N. A peland MA, Foreyt JP, Graves K, Haffner 83. DAFNE Study Group. Training in flexi- clinical trial of the effects of dietary pat- SM, Harrison B, Hill JO, Horton ES, Ja-care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S51
    • Standards of Medical Care kicic J, Jeffery RW, Johnson KC, Kahn S, prevention of diabetes and related com- systematic review and methodological Kelley DE, Kitabchi AE, Knowler WC, plications. Diabetes Care 2002;25:148 – critique of the literature. Arch Intern Lewis CE, Maschak-Carey BJ, Montgom- 198 Med 2004;164:1641–1649 ery B, Nathan DM, Patricio J, Peters A, 110. Buchwald H, Estok R, Fahrbach K, Banel 121. Funnell MM, Brown TL, Childs BP, Haas Redmon JB, Reeves RS, Ryan DH, Safford D, Jensen MD, Pories WJ, Bantle JP, LB, Hosey GM, Jensen B, Maryniuk M, M, Van Dorsten B, Wadden TA, Wagen- Sledge I. Weight and type 2 diabetes af- Peyrot M, Piette JD, Reader D, Siminerio knecht L, Wesche-Thobaben J, Wing RR, ter bariatric surgery: systematic review LM, Weinger K, Weiss MA. National Yanovski SZ. Reduction in weight and car- and meta-analysis. Am J Med 2009;122: standards for diabetes self-management diovascular disease risk factors in individ- 248 –256 education. Diabetes Care 2007;30: uals with type 2 diabetes: one-year results 111. Dixon JB, O’Brien PE, Playfair J, Chap- 1630 –1637 of the look AHEAD trial. Diabetes Care man L, Schachter LM, Skinner S, Proi- 122. Mulcahy K, Maryniuk M, Peeples M, Pey- 2007;30:1374 –1383 etto J, Bailey M, Anderson M. Adjustable rot M, Tomky D, Weaver T, Yarborough P.102. Foster GD, Wyatt HR, Hill JO, gastric banding and conventional ther- Diabetes self-management education core McGuckin BG, Brill C, Mohammed BS, apy for type 2 diabetes: a randomized outcomes measures. Diabetes Educ Szapary PO, Rader DJ, Edman JS, Klein controlled trial. JAMA 2008;299:316 – 29:768- 2003;84:787 S. A randomized trial of a low-carbohy- 323 123. Glasgow RE, Peeples M, Skovlund SE. drate diet for obesity. N Engl J Med 112. Buchwald H, Estok R, Fahrbach K, Banel Where is the patient in diabetes perfor- 2003;348:2082–2090 D, Sledge I. Trends in mortality in bari- mance measures? The case for including103. Stern L, Iqbal N, Seshadri P, Chicano atric surgery: a systematic review and patient-centered and self-management KL, Daily DA, McGrory J, Williams M, meta-analysis. Surgery 2007;142:621– measures. Diabetes Care 2008;31:1046 – Gracely EJ, Samaha FF. The effects of 632 1050 low-carbohydrate versus conventional 113. Sjostrom L, Narbro K, Sjostrom CD, ¨ ¨ ¨ ¨ 124. Barker JM, Goehrig SH, Barriga K, Hoff- weight loss diets in severely obese Karason K, Larsson B, Wedel H, Lystig man M, Slover R, Eisenbarth GS, Norris adults: one-year follow-up of a random- T, Sullivan M, Bouchard C, Carlsson B, JM, Klingensmith GJ, Rewers M, DAISY ized trial. Ann Intern Med 2004;140: Bengtsson C, Dahlgren S, Gummesson study. Clinical characteristics of chil- 778 –785 A, Jacobson P, Karlsson J, Lindroos AK, dren diagnosed with type 1 diabetes104. Gardner CD, Kiazand A, Alhassan S, Lonroth H, Naslund I, Olbers T, Stenlof ¨ ¨ ¨ through intensive screening and follow- Kim S, Stafford RS, Balise RR, Kraemer K, Torgerson J, Agren G, Carlsson LM, up. Diabetes Care 2004;27:1399 –1404 HC, King AC. Comparison of the At- Swedish Obese Subjects Study. Effects of 125. Cochran J, Conn VS. Meta-analysis of kins, Zone, Ornish, and LEARN diets bariatric surgery on mortality in Swedish quality of life outcomes following diabe- for change in weight and related risk obese subjects. N Engl J Med 2007;357: tes self-management training. Diabetes factors among overweight premeno- 741–752 Educ 2008;34:815– 823 pausal women. JAMA 2007;297:969 – 114. Piette JD, Glasgow RE: Sttategies for im- 126. Fisher EB, Thorpe CT, Devellis BM, De- 977 proving behavioral and health outcomes vellis RF. Healthy coping, negative emo-105. Nordmann AJ, Nordmann A, Briel M, among people with diabetes: self man- tions, and diabetes management: a Keller U, Yancy WS, Jr, Brehm BJ, agement education. In Evidence-Based systematic review and appraisal. Diabe- Bucher HC. Effects of low-carbohydrate Diabetes Care. Gerstein HC, Hayes RB, tes Educ 2007;33:1080 –1103 vs low-fat diets on weight loss and car- Eds. Ontario, Canada, BC Decker, 2000 127. Robbins JM, Thatcher GE, Webb DA, diovascular risk factors: a meta-analysis 115. Norris SL, Engelgau MM, Narayan KM. Valdmanis VG. Nutritionist visits, diabe- of randomized controlled trials. Arch In- Effectiveness of self-management train- tes classes, and hospitalization rates and tern Med 2006;166:285–293 ing in type 2 diabetes: a systematic re- charges: the Urban Diabetes Study. Dia-106. Institute of Medicine: DIetary Reference view of randomized controlled trials. betes Care 2008;31:655– 660 Intakes: Energy, Carbohydrate, Fiber, Fat, Diabetes Care 2001;24:561–587 128. Renders CM, Valk GD, Griffin SJ, Wag- Fatty Acids, Cholesterol, Protein, and 116. Norris SL, Lau J, Smith SJ, Schmid CH, ner EH, Eijk Van JT, Assendelft WJ. In- Amino Acids. Washington, DC, National Engelgau MM. Self-management educa- terventions to improve the management Academies Press, 2002 tion for adults with type 2 diabetes: a of diabetes in primary care, outpatient,107. Barnard ND, Cohen J, Jenkins DJ, Turner- meta-analysis of the effect on glycemic and community settings: a systematic re- McGrievy G, Gloede L, Jaster B, Seidl K, control. Diabetes Care 2002;25:1159 – view. Diabetes Care 2001;24:1821– Green AA, Talpers S. A low-fat vegan 1171 1833 diet improves glycemic control and car- 117. Gary TL, Genkinger JM, Guallar E, Pey- 129. Polonsky WH, Earles J, Smith S, Pease diovascular risk factors in a randomized rot M, Brancati FL. Meta-analysis of ran- DJ, Macmillan M, Christensen R, Taylor clinical trial in individuals with type 2 domized educational and behavioral T, Dickert J, Jackson RA. Integrating diabetes. Diabetes Care 2006;29:1777– interventions in type 2 diabetes. Diabe- medical management with diabetes self- 1783 tes Educ 2003;29:488 –501 management training: a randomized108. Turner-McGrievy GM, Barnard ND, Co- 118. Steed L, Cooke D, Newman S. A system- control trial of the Diabetes Outpatient hen J, Jenkins DJ, Gloede L, Green AA. atic review of psychosocial outcomes Intensive Treatment program. Diabetes Changes in nutrient intake and dietary following education, self-management Care 2003;26:3048 –3053 quality among participants with type 2 and psychological interventions in dia- 130. Anderson RM, Funnell MM, Nwankwo diabetes following a low-fat vegan diet or betes mellitus. Patient Educ Couns R, Gillard ML, Oh M, Fitzgerald JT. a conventional diabetes diet for 22 2003;51:5–15 Evaluating a problem-based empower- weeks. J Am Diet Assoc 2008;108: 119. Ellis SE, Speroff T, Dittus RS, Brown A, ment program for African Americans 1636 –1645 Pichert JW, Elasy TA. Diabetes patient with diabetes: results of a randomized109. Franz MJ, Bantle JP, Beebe CA, Brunzell education: a meta-analysis and meta-re- controlled trial. Ethn Dis 2005;15: JD, Chiasson JL, Garg A, Holzmeister gression. Patient Educ Couns 2004;52: 671– 678 LA, Hoogwerf B, Mayer-Davis E, Moora- 97–105 131. Brown SA, Blozis SA, Kouzekanani K, dian AD, Purnell JQ, Wheeler M. Evi- 120. Warsi A, Wang PS, LaValley MP, Avorn Garcia AA, Winchell M, Hanis CL. Dos- dence-based nutrition principles and J, Solomon DH. Self-management edu- age effects of diabetes self-management recommendations for the treatment and cation programs in chronic disease: a education for Mexican Americans: theS52 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement Starr County Border Health Initiative. diabetes mellitus: a meta-analysis of 156. Aiello LP, Wong J, Cavallerano J, Bursell Diabetes Care 2005;28:527–532 controlledclinicaltrials.JAMA2001;286: SE, Aiello LM: Retinopathy. In Handbook132. Glazier RH, Bajcar J, Kennie NR, Willson 1218 –1227 of Exercise in Diabetes. 2nd ed. Ru- K. A systematic review of interventions 146. Boule NG, Kenny GP, Haddad E, Wells ´ derman N, Devlin JT, Kriska A, Eds. to improve diabetes care in socially dis- GA, Sigal RJ. Meta-analysis of the effect Alexandria, VA, American Diabetes As- advantaged populations. Diabetes Care of structured exercise training on cardio- sociation, 2002, p. 401– 413 2006;29:1675–1688 respiratory fitness in Type 2 diabetes 157. Lemaster JW, Reiber GE, Smith DG,133. Sarkisian CA, Brown AF, Norris KC, mellitus. Diabetologia 2003;46:1071– Heagerty PJ, Wallace C. Daily weight- Wintz RL, Mangione CM. A systematic 1081 bearing activity does not increase the review of diabetes self-care interventions 147. U.S. Department of Health and Human risk of diabetic foot ulcers. Med Sci for older, African American, or Latino Services. 2008 Physical Activity Guide- Sports Exerc 2003;35:1093–1099 adults. Diabetes Educ 2003;29:467–479 lines for Americans. Atlanta, GA, 158. Vinik A, Erbas T: Neuropathy. In Hand-134. Chodosh J, Morton SC, Mojica W, Ma- Centers for Disease Control and Pre- book of Exercise in Diabetes. 2nd ed. Ru- glione M, Suttorp MJ, Hilton L, Rhodes vention, 2008 derman N, Devlin JT, Kriska A, Eds. S, Shekelle P. Meta-analysis: chronic dis- 148. Cauza E, Hanusch-Enserer U, Strasser B, Alexandria, VA, American Diabetes As- ease self-management programs for Ludvik B, Metz-Schimmerl S, Pacini G, sociation, 2002, p. 463– 496 older adults. Ann Intern Med 2005;143: Wagner O, Georg P, Prager R, Kostner K, 159. Wackers FJ, Young LH, Inzucchi SE, 427– 438 Dunky A, Haber P. The relative benefits Chyun DA, Davey JA, Barrett EJ,135. Peyrot M, Rubin RR. Behavioral and psy- of endurance and strength training on Taillefer R, Wittlin SD, Heller GV, Filip- chosocial interventions in diabetes: a the metabolic factors and muscle func- chuk N, Engel S, Ratner RE, Iskandrian conceptual review. Diabetes Care 2007; tion of people with type 2 diabetes mel- AE, Detection of Ischemia in Asymp- 30:2433–2440 litus. Arch Phys Med Rehabil 2005;86: tomatic Diabetics Investigators. Detec-136. Rickheim PL, Weaver TW, Flader JL, 1527–1533 tion of silent myocardial ischemia in Kendall DM. Assessment of group versus 149. Dunstan DW, Daly RM, Owen N, Jolley asymptomatic diabetic subjects: the individual diabetes education: a ran- D, De Courten M, Shaw J, Zimmet P. DIAD study. Diabetes Care 2004;27: domized study. Diabetes Care 2002;25: High-intensity resistance training im- 1954 –1961 269 –274 proves glycemic control in older patients 160. Valensi P, Sachs RN, Harfouche B,137. Trento M, Passera P, Borgo E, Tomalino with type 2 diabetes. Diabetes Care Lormeau B, Paries J, Cosson E, Paycha F, M, Bajardi M, Cavallo F, Porta M. A 2002;25:1729 –1736 Leutenegger M, Attali JR. Predictive 5-year randomized controlled study of 150. Castaneda C, Layne JE, Munoz-Orians value of cardiac autonomic neuropathy learning, problem solving ability, and L, Gordon PL, Walsmith J, Foldvari M, in diabetic patients with or without si- quality of life modifications in people Roubenoff R, Tucker KL, Nelson ME. A lent myocardial ischemia. Diabetes Care with type 2 diabetes managed by group randomized controlled trial of resistance 2001;24:339 –343 care. Diabetes Care 2004;27:670 – 675 exercise training to improve glycemic 161. Mogensen CE: Nephropathy. In Hand-138. Deakin T, McShane CE, Cade JE, Wil- control in older adults with type 2 dia- book of Exercise in Diabetes. 2nd ed. Ru- liams RD: Group based training for self- betes. Diabetes Care 2002;25:2335– derman N, Devlin JT, Kriska A, Eds. management strategies in people with 2341 Alexandria, VA, American Diabetes As- type 2 diabetes mellitus. Cochrane Da- 151. Sigal RJ, Kenny GP, Boule NG, Wells ´ sociation, 2002, p. 433– 449 tabase Syst Rev CD003417, 2005 GA, Prud’homme D, Fortier M, Reid RD, 162. Anderson RJ, Grigsby AB, Freedland KE,139. Heisler, M. Building Peer Support Pro- Tulloch H, Coyle D, Phillips P, Jennings de Groot M, McGill JB, Clouse RE, Lust- grams to Manage Chronic Disease: Seven A, Jaffey J. Effects of aerobic training, re- man PJ. Anxiety and poor glycemic con- Models for Success. Oakland, CA, Califor- sistance training, or both on glycemic trol: a meta-analytic review of the nia Health Care Foundation, 2006 control in type 2 diabetes: a randomized literature. Int J Psychiatry Med 2002;32:140. Foster G, Taylor SJ, Eldridge SE, Ramsay trial. Ann Intern Med 2007;147: 235–247 J, Griffiths CJ: Self-management educa- 357–369 163. Delahanty LM, Grant RW, Wittenberg E, tion programmes by lay leaders for peo- 152. Bax JJ, Young LH, Frye RL, Bonow RO, Bosch JL, Wexler DJ, Cagliero E, Meigs ple with chronic conditions. Cochrane Steinberg HO, Barrett EJ, ADA. Screen- JB. Association of diabetes-related emo- Database Syst Rev CD005108, 2007 ing for coronary artery disease in pa- tional distress with diabetes treatment in141. Norris SL, Chowdhury FM, Van Le K, tients with diabetes. Diabetes Care 2007; primary care patients with Type 2 diabe- Horsley T, Brownstein JN, Zhang X, Jack 30:2729 –2736 tes. Diabet Med 2007;24:48 –54 L Jr, Satterfield DW. Effectiveness of 153. Berger M, Berchtold P, Cuppers HJ, ¨ 164. American Diabetes Association: Psycho- community health workers in the care of Drost H, Kley HK, Muller WA, ¨ social factors affecting adherence, qual- persons with diabetes. Diabet Med Wiegelmann W, Zimmerman-Telschow ity of life, and well-being: Helping 2006;23:544 –556 H, Gries FA, Kruskemper HL, Zimmer- ¨ Patients cope. In Medical Management of142. Duncan I, Birkmeyer C, Coughlin S, Li mann H. Metabolic and hormonal ef- Type 1 Diabetes. 5 ed. Francine R. Kauf- QE, Sherr D, Boren S. Assessing the fects of muscular exercise in juvenile man, Ed. Alexandria, VA, American Di- value of diabetes education. Diabetes type diabetics. Diabetologia 1977;13: abetes Association, 2008, p. 173–193 Educ 2009;35:752–760 355–365 165. Fisher L, Skaff MM, Mullan JT, Arean P,143. Sigal RJ, Kenny GP, Wasserman DH, 154. American Diabetes Association: Physical Mohr D, Masharani U, Glasgow R, Lau- Castaneda-Sceppa C. Physical activity/ activity/exercise and diabetes (Position rencin G. Clinical depression versus dis- exercise and type 2 diabetes. Diabetes Statement). Diabetes Care 2004; tress among patients with type 2 Care 2004;27:2518 –2539 27(Suppl. 1):S58 –S62 diabetes: not just a question of seman-144. Wasserman DH, Zinman B. Exercise in 155. Berger M: Adjustment of insulin and oral tics. Diabetes Care 2007;30:542–548 individuals with IDDM. Diabetes Care agent therapy. In Handbook of Exercise in 166. Surwit RS, Schneider MS, Feinglos MN. 1994;17:924 –937 Diabetes. 2nd ed. Ruderman N, Devlin Stress and diabetes mellitus. Diabetes145. Boule NG, Haddad E, Kenny GP, Wells ´ JTSSH, Krisska A, Eds. Alexandria, VA, Care 1992;15:1413–1422 GA, Sigal RJ. Effects of exercise on gly- American Diabetes Association, 2002, p. 167. McCulloch DK, Glasgow RE, Hampson cemic control and body mass in type 2 365–376 SE, Wagner E. A systematic approach tocare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S53
    • Standards of Medical Care diabetes management in the post-DCCT 183. Buse JB, Ginsberg HN, Bakris GL, Clark ity: a meta-analysis of individual data for era. Diabetes Care 1994;17:765–769 NG, Costa F, Eckel R, Fonseca V, Ger- one million adults in 61 prospective168. Rubin RR, Peyrot M. Psychological is- stein HC, Grundy S, Nesto RW, Pignone studies. Lancet 2002;360:1903–1913 sues and treatments for people with di- MP, Plutzky J, Porte D, Redberg R, Stit- 191. Stamler J, Vaccaro O, Neaton JD, Went- abetes. J Clin Psychol 2001;57:457– 478 zel KF, Stone NJ, American Heart Asso- worth D. Diabetes, other risk factors,169. Jacobson AM. Depression and diabetes. ciation, American Diabetes Association. and 12-yr cardiovascular mortality for Diabetes Care 1993;16:1621–1623 Primary prevention of cardiovascular men screened in the Multiple Risk Fac-170. Lustman PJ, Griffith LS, Clouse RE, diseases in people with diabetes melli- tor Intervention Trial. Diabetes Care Cryer PE. Psychiatric illness in diabetes tus: a scientific statement from the 1993;16:434 – 444 mellitus. Relationship to symptoms and American Heart Association and the 192. Cushman WC, Grimm RH Jr, Cutler JA, glucose control. J Nerv Ment Dis 1986; American Diabetes Association. Diabe- Evans GW, Capes S, Corson MA, Sadler 174:736 –742 tes Care 2007;30:162–172 LS, Alderman MH, Peterson K, Bertoni171. Blonde L, Merilainen M, Karwe V, 184. Chobanian AV, Bakris GL, Black HR, A, Basile JN, ACCORD Study Group: Ra- Raskin P, TITRATE Study Group. Pa- Cushman WC, Green LA, Izzo JL Jr, tionale and design for the blood pressure tient-directed titration for achieving gly- Jones DW, Materson BJ, Oparil S, intervention of the Action to Control caemic goals using a once-daily basal Wright JT Jr, Roccella EJ, National Cardiovascular Risk in Diabetes (AC- insulin analogue: an assessment of two Heart, Lung, and Blood Institute Joint CORD) trial. Am J Cardiol 2007;99:44i– different fasting plasma glucose targets National Committee on Prevention, De- 55i -the TITRATE study. Diabetes Obes tection, Evaluation, and Treatment of 193. Sacks FM, Svetkey LP, Vollmer WM, Ap- Metab 2009;11:623– 631 High Blood Pressure, National High Blood pel LJ, Bray GA, Harsha D, Obarzanek E,172. American Diabetes Association: Hyper- Pressure Education Program Coordinat- Conlin PR, Miller ER 3rd, Simons-Mor- glycemic crises in diabetes. Diabetes ing Committee. The Seventh Report of the ton DG, Karanja N, Lin PH, DASH-So- Care 2004;27 (Suppl. 1):S94 –S102 Joint National Committee on Prevention, dium Collaborative Research Group.173. Kitabchi AE, Umpierrez GE, Miles JM, Detection, Evaluation, and Treatment of Effects on blood pressure of reduced di- Fisher JN. Hyperglycemic crises in adult High Blood Pressure: the JNC 7 report. etary sodium and the Dietary Ap- patients with diabetes. Diabetes Care JAMA 2003;289:2560 –2572 proaches to Stop Hypertension (DASH) 2009;32:1335–1343 185. Bobrie G, Chatellier G, Genes N, Clerson diet. DASH-Sodium Collaborative Re-174. Cryer PE. Hypoglycaemia: the limiting P, Vaur L, Vaisse B, Menard J, Mallion search Group. N Engl J Med 2001;344: factor in the glycaemic management of JM. Cardiovascular prognosis of 3–10 Type I and Type II diabetes. Diabetolo- “masked hypertension” detected by 194. Tatti P, Pahor M, Byington RP, Di Mauro gia 2002;45:937–948 blood pressure self-measurement in el- P, Guarisco R, Strollo G, Strollo F. Out-175. Gannon MC, Nuttall FQ: Protein and derly treated hypertensive patients. come results of the Fosinopril Versus Diabetes. In American Diabetes Associa- JAMA 2004;291:1342–1349 Amlodipine Cardiovascular Events Ran- tion Guide to Medical Nutrition Therapy 186. Sega R, Facchetti R, Bombelli M, Cesana domized Trial (FACET) in patients with for Diabetes. Franz MJ, Bantle JP, Eds. G, Corrao G, Grassi G, Mancia G. Prog- hypertension and NIDDM. Diabetes Alexandria, VA, American Diabetes As- nostic value of ambulatory and home Care 1998;21:597– 603 sociation, 1999, p. 107–125 blood pressures compared with office 195. Estacio RO, Jeffers BW, Hiatt WR, Big-176. Cryer PE. Diverse causes of hypoglyce- blood pressure in the general popula- gerstaff SL, Gifford N, Schrier RW. The mia-associated autonomic failure in dia- tion: follow-up results from the Pres- effect of nisoldipine as compared with betes. N Engl J Med 2004;350:2272– sioni Arteriose Monitorate e Loro enalapril on cardiovascular outcomes in 2279 Associazioni (PAMELA) study. Circula- patients with non-insulin-dependent di-177. Cryer PE, Davis SN, Shamoon H. Hypo- tion 2005;111:1777–1783 abetes and hypertension. N Engl J Med glycemia in diabetes. Diabetes Care 187. UKPDS: Tight blood pressure control 1998;338:645– 652 2003;26:1902–1912 and risk of macrovascular and microvas- 196. Schrier RW, Estacio RO, Mehler PS, Hi-178. Smith SA, Poland GA. Use of influenza cular complications in type 2 diabetes: att WR. Appropriate blood pressure and pneumococcal vaccines in people UKPDS 38. UK Prospective Diabetes control in hypertensive and normoten- with diabetes. Diabetes Care 2000;23: Study Group. BMJ 1998;317:703–713 sive type 2 diabetes mellitus: a summary 95–108 188. Hansson L, Zanchetti A, Carruthers SG, of the ABCD trial. Nat Clin Pract Neph-179. Colquhoun AJ, Nicholson KG, Botha JL, Dahlof B, Elmfeldt D, Julius S, Menard J, ¨ ´ rol 2007;3:428 – 438 Raymond NT. Effectiveness of influenza Rahn KH, Wedel H, Westerling S. Ef- 197. ALLHAT Officers and Coordinators for vaccine in reducing hospital admissions fects of intensive blood-pressure lower- the ALLHAT Collaborative Research in people with diabetes. Epidemiol In- ing and low-dose aspirin in patients Group. The Antihypertensive and Lipid- fect 1997;119:335–341 with hypertension: principal results of Lowering Treatment to Prevent Heart180. Bridges CB, Fukuda K, Uyeki TM, Cox the Hypertension Optimal Treatment Attack Trial: the Antihypertensive and NJ, Singleton JA. Prevention and control (HOT) randomised trial. HOT Study Lipid-Lowering Treatment to Prevent of influenza. Recommendations of the Group. Lancet 1998;351:1755–1762 Heart Attack Trial (ALLHAT). JAMA Advisory Committee on Immunization 189. Adler AI, Stratton IM, Neil HA, Yudkin 2002;288:2981–2997 Practices (ACIP). MMWR Recomm Rep JS, Matthews DR, Cull CA, Wright AD, 198. Psaty BM, Lumley T, Furberg CD, Schel- 2002;51:1–31 Turner RC, Holman RR. Association of lenbaum G, Pahor M, Alderman MH,181. American Diabetes Association: Influ- systolic blood pressure with macrovas- Weiss NS. Health outcomes associated enza and pneumococcal immunization cular and microvascular complications with various antihypertensive therapies in diabetes (Position Statement). Diabe- of type 2 diabetes (UKPDS 36): prospec- used as first-line agents: a network meta- tes Care 2004;27(Suppl. 1):S111–S113 tive observational study. BMJ 2000;321: analysis. JAMA 2003;289:2534 –2544182. Gaede P, Lund-Andersen H, Parving 412– 419 199. Effects of ramipril on cardiovascular and HH, Pedersen O. Effect of a multifacto- 190. Lewington S, Clarke R, Qizilbash N, microvascular outcomes in people with rial intervention on mortality in type 2 Peto R, Collins R, Prospective Studies diabetes mellitus: results of the HOPE diabetes. N Engl J Med 2008;358:580 – Collaboration. Age-specific relevance of study and MICRO-HOPE substudy: 591 usual blood pressure to vascular mortal- Heart Outcomes Prevention EvaluationS54 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement Study Investigators. Lancet 2000;355: Hypertension and Diabetes Executive heart disease and diabetes: the Treating 253–259 Committees Working Group. Am J Kid- to New Targets (TNT) study. Diabetes200. Pfeffer MA, Swedberg K, Granger CB, ney Dis 2000;36:646 – 661 Care 2006;29:1220 –1226 Held P, McMurray JJ, Michelson EL, 207. Psaty BM, Smith NL, Siscovick DS, Ko- 215. Sever PS, Poulter NR, Dahlof B, Wedel ¨ Olofsson B, Ostergren J, Yusuf S, Pocock epsell TD, Weiss NS, Heckbert SR, Le- H, Collins R, Beevers G, Caulfield M, S, CHARM Investigators and Commit- maitre RN, Wagner EH, Furberg CD. Kjeldsen SE, Kristinsson A, McInnes GT, tees. Effects of candesartan on mortality Health outcomes associated with antihy- Mehlsen J, Nieminen M, O’Brien E, Os- and morbidity in patients with chronic pertensive therapies used as first-line tergren J. Reduction in cardiovascular heart failure: the CHARM-Overall pro- agents: a systematic review and meta- events with atorvastatin in 2,532 pa- gramme. Lancet 2003;362:759 –766 analysis. JAMA 1997;277:739 –745 tients with type 2 diabetes: Anglo-Scan-201. Granger CB, McMurray JJ, Yusuf S, Held 208. Patel A, ADVANCE Collaborative dinavian Cardiac Outcomes Trial–lipid- P, Michelson EL, Olofsson B, Ostergren Group, MacMahon S, Chalmers J, Neal lowering arm (ASCOT-LLA). Diabetes J, Pfeffer MA, Swedberg K, CHARM In- B, Woodward M, Billot L, Harrap S, Care 2005;28:1151–1157 vestigators and Committees. Effects of Poulter N, Marre M, Cooper M, Glasziou 216. Knopp RH, d’Emden M, Smilde JG, Po- candesartan in patients with chronic P, Grobbee DE, Hamet P, Heller S, Liu cock SJ. Efficacy and safety of atorvasta- heart failure and reduced left-ventricular LS, Mancia G, Mogensen CE, Pan CY, tin in the prevention of cardiovascular systolic function intolerant to angioten- Rodgers A, Williams B. Effects of a fixed end points in subjects with type 2 di- sin-converting-enzyme inhibitors: the combination of perindopril and indap- abetes: the Atorvastatin Study for Pre- CHARM-Alternative trial. Lancet 2003; amide on macrovascular and microvas- vention of Coronary Heart Disease 362:772–776 cular outcomes in patients with type 2 Endpoints in non-insulin-dependent di-202. McMurray JJ, Ostergren J, Swedberg K, diabetes mellitus (the ADVANCE trial): abetes mellitus (ASPEN). Diabetes Care Granger CB, Held P, Michelson EL, a randomised controlled trial. Lancet 2006;29:1478 –1485 Olofsson B, Yusuf S, Pfeffer MA, 2007;370:829 – 840 217. Singh IM, Shishehbor MH, Ansell BJ. CHARM Investigators and Committees. 209. Sibai BM. Treatment of hypertension in High-density lipoprotein as a therapeu- Effects of candesartan in patients with pregnant women. N Engl J Med 1996; tic target: a systematic review. JAMA chronic heart failure and reduced left- 335:257–265 2007;298:786 –798 ventricular systolic function taking an- 210. Baigent C, Keech A, Kearney PM, Black- 218. Canner PL, Berge KG, Wenger NK, giotensin-converting-enzyme well L, Buck G, Pollicino C, Kirby A, Stamler J, Friedman L, Prineas RJ, inhibitors: the CHARM-Added trial. Sourjina T, Peto R, Collins R, Simes R, Friedewald W. Fifteen year mortality in Lancet 2003;362:767–771 Cholesterol Treatment Trialists’ (CTT) Coronary Drug Project patients: long-203. Lindholm LH, Ibsen H, Dahlof B, De- ¨ Collaborators. Efficacy and safety of term benefit with niacin. J Am Coll Car- vereux RB, Beevers G, de Faire U, Fyhr- cholesterol-lowering treatment: pro- diol 1986;8:1245–1255 quist F, Julius S, Kjeldsen SE, spective meta-analysis of data from 219. Rubins HB, Robins SJ, Collins D, Fye CL, Kristiansson K, Lederballe-Pedersen O, 90,056 participants in 14 randomised Anderson JW, Elam MB, Faas FH, Lin- Nieminen MS, Omvik P, Oparil S, trials of statins. Lancet 2005;366:1267– ares E, Schaefer EJ, Schectman G, Wilt Wedel H, Aurup P, Edelman J, Snapinn 1278 TJ, Wittes J. Gemfibrozil for the second- S, LIFE Study Group. Cardiovascular 211. Pyorala K, Pedersen TR, Kjekshus J, ˘ ¨ ¨ ary prevention of coronary heart disease morbidity and mortality in patients with Faergeman O, Olsson AG, Thorgeirsson in men with low levels of high-density diabetes in the Losartan Intervention For G. Cholesterol lowering with simvasta- lipoprotein cholesterol. Veterans Affairs Endpoint reduction in hypertension tin improves prognosis of diabetic pa- High-Density Lipoprotein Cholesterol study (LIFE): a randomised trial against tients with coronary heart disease: a Intervention Trial Study Group. N Engl atenolol. Lancet 2002;359:1004 –1010 subgroup analysis of the Scandinavian J Med 1999;341:410 – 418204. Berl T, Hunsicker LG, Lewis JB, Pfeffer Simvastatin Survival Study (4S). Diabe- 220. Frick MH, Elo O, Haapa K, Heinonen MA, Porush JG, Rouleau JL, Drury PL, tes Care 1997;20:614 – 620 OP, Heinsalmi P, Helo P, Huttunen JK, Esmatjes E, Hricik D, Parikh CR, Raz I, 212. Collins R, Armitage J, Parish S, Sleigh P, Kaitaniemi P, Koskinen P, Manninen V: Vanhille P, Wiegmann TB, Wolfe BM, Peto R, Heart Protection Study Collabo- Helsinki Heart Study: primary-preven- Locatelli F, Goldhaber SZ, Lewis EJ, rative Group: MRC/BHF Heart Protec- tion trial with gemfibrozil in middle- Irbesartan Diabetic Nephropathy Trial. tion Study of cholesterol-lowering with aged men with dyslipidemia: safety of Collaborative Study Group. Collabora- simvastatin in 5963 people with diabe- treatment, changes in risk factors, and tive Study Group. Cardiovascular out- tes: a randomised placebo-controlled incidence of coronary heart disease. comes in the Irbesartan Diabetic trial. Lancet 2003;361:2005–2016 N Engl J Med 1987;317:1237–1245 Nephropathy Trial of patients with type 213. Goldberg RB, Mellies MJ, Sacks FM, 221. Keech A, Simes RJ, Barter P, Best J, Scott 2 diabetes and overt nephropathy. Ann Moye LA, Howard BV, Howard WJ, ´ R, Taskinen MR, Forder P, Pillai A, Davis Intern Med 2003;138:542–549 Davis BR, Cole TG, Pfeffer MA, Braun- T, Glasziou P, Drury P, Kesaniemi YA, ¨205. Laffel LM, McGill JB, Gans DJ. The ben- wald E. Cardiovascular events and their Sullivan D, Hunt D, Colman P, d’Emden eficial effect of angiotensin-converting reduction with pravastatin in diabetic M, Whiting M, Ehnholm C, Laakso M, enzyme inhibition with captopril on di- and glucose-intolerant myocardial in- FIELD study investigators. Effects of abetic nephropathy in normotensive farction survivors with average choles- long-term fenofibrate therapy on cardio- IDDM patients with microalbuminuria. terol levels: subgroup analyses in the vascular events in 9795 people with type North American Microalbuminuria cholesterol and recurrent events (CARE) 2 diabetes mellitus (the FIELD study): Study Group. Am J Med 1995;99:497– trial. The Care Investigators. Circulation randomised controlled trial. Lancet 504 1998;98:2513–2519 2005;366:1849 –1861206. Bakris GL, Williams M, Dworkin L, El- 214. Shepherd J, Barter P, Carmena R, Deed- 222. Expert Panel on Detection, Evaluation, liott WJ, Epstein M, Toto R, Tuttle K, wania P, Fruchart JC, Haffner S, Hsia J, and Treatment of High Blood Choles- Douglas J, Hsueh W, Sowers J. Preserv- Breazna A, LaRosa J, Grundy S, Waters terol in Adults: Executive Summary of ing renal function in adults with hyper- D. Effect of lowering LDL cholesterol The Third Report of The National Cho- tension and diabetes: a consensus substantially below currently recom- lesterol Education Program (NCEP) Ex- approach: National Kidney Foundation mended levels in patients with coronary pert Panel on Detection, Evaluation,care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S55
    • Standards of Medical Care And Treatment of High Blood Choles- study: A randomized trial. Arterial Dis- Force recommendation statement. Ann terol In Adults (Adult Treatment Panel ease Multiple Intervention Trial. JAMA Intern Med 2009;150:396 – 404 III). JAMA 2001;285:2486 –2497 2000;284:1263–1270 239. Ogawa H, Nakayama M, Morimoto T,223. Hayward RA, Hofer TP, Vijan S. Nar- 231. Grundy SM, Vega GL, McGovern ME, Uemura S, Kanauchi M, Doi N, Jinnou- rative review: lack of evidence for rec- Tulloch BR, Kendall DM, Fitz-Patrick D, chi H, Sugiyama S, Saito Y, Japanese Pri- ommended low-density lipoprotein Ganda OP, Rosenson RS, Buse JB, Rob- mary Prevention of Atherosclerosis With treatment targets: a solvable problem. ertson DD, Sheehan JP, Diabetes Multi- Aspirin for Diabetes (JPAD) Trial Inves- Ann Intern Med 2006;145:520 –530 center Research Group. Efficacy, safety, tigators. Low-dose aspirin for primary224. Cannon CP, Braunwald E, McCabe CH, and tolerability of once-daily niacin for prevention of atherosclerotic events in Rader DJ, Rouleau JL, Belder R, Joyal SV, the treatment of dyslipidemia associated patients with type 2 diabetes: a random- Hill KA, Pfeffer MA, Skene AM, Prava- with type 2 diabetes: results of the as- ized controlled trial. JAMA 2008;300: statin or Atorvastatin Evaluation and sessment of diabetes control and evalu- 2134 –2141 Infection Therapy-Thrombolysis in ation of the efficacy of niaspan trial. Arch 240. Belch J, MacCuish A, Campbell I, Cobbe Myocardial Infarction 22 Investigators. Intern Med 2002;162:1568 –1576 S, Taylor R, Prescott R, Lee R, Bancroft J, Intensive versus moderate lipid lowering 232. Jones PH, Davidson MH. Reporting rate MacEwan S, Shepherd J, Macfarlane P, with statins after acute coronary syn- of rhabdomyolysis with fenofibrate Morris A, Jung R, Kelly C, Connacher A, dromes. N Engl J Med 2004;350:1495– statin versus gemfibrozil any statin. Peden N, Jamieson A, Matthews D, Leese 1504 Am J Cardiol 2005;95:120 –122 G, McKnight J, O’Brien I, Semple C, Pet-225. de Lemos JA, Blazing MA, Wiviott SD, 233. Brunzell JD, Davidson M, Furberg CD, rie J, Gordon D, Pringle S, MacWalter R. Lewis EF, Fox KA, White HD, Rouleau Goldberg RB, Howard BV, Stein JH, Wit- The prevention of progression of arterial JL, Pedersen TR, Gardner LH, Mukher- ztum JL, American Diabetes Association, disease and diabetes (POPADAD) trial: jee R, Ramsey KE, Palmisano J, Bilhei- American College of Cardiology Foun- factorial randomised placebo controlled mer DW, Pfeffer MA, Califf RM, dation. Lipoprotein management in trial of aspirin and antioxidants in pa- Braunwald E, A to Z Investigators. Early patients with cardiometabolic risk: con- tients with diabetes and asymptomatic intensive vs a delayed conservative sim- sensus statement from the American Di- peripheral arterial disease. BMJ 2008; vastatin strategy in patients with acute abetes Association and the American 337:a1840 coronary syndromes: phase Z of the A to College of Cardiology Foundation. Dia- 241. Pignone M, Earnshaw S, Tice JA, Z trial. JAMA 2004;292:1307–1316 betes Care 2008;31:811– 822 Pletcher MJ. Aspirin, statins, or both226. Nissen SE, Tuzcu EM, Schoenhagen P, 234. Colhoun HM, Betteridge DJ, Durrington drugs for the primary prevention of cor- Brown BG, Ganz P, Vogel RA, Crowe T, PN, Hitman GA, Neil HA, Livingstone SJ, onary heart disease events in men: a Howard G, Cooper CJ, Brodie B, Grines Thomason MJ, Mackness MI, Charlton- cost-utility analysis. Ann Intern Med CL, DeMaria AN, REVERSAL Investiga- Menys V, Fuller JH, CARDS investigators. 2006;144:326 –336 tors. Effect of intensive compared with Primary prevention of cardiovascular dis- 242. Campbell CL, Smyth S, Montalescot G, moderate lipid-lowering therapy on pro- ease with atorvastatin in type 2 diabetes in Steinhubl SR. Aspirin dose for the pre- gression of coronary atherosclerosis: a the Collaborative Atorvastatin Diabetes vention of cardiovascular disease: a sys- randomized controlled trial. JAMA Study (CARDS): multicentre randomised tematic review. JAMA 2007;297:2018 – 2004;291:1071–1080 placebo-controlled trial. Lancet 2004;364: 2024227. Grundy SM, Cleeman JI, Merz CN, 685– 696 243. Davì G, Patrono C. Platelet activation Brewer HB Jr, Clark LT, Hunninghake 235. Buse JB, Ginsberg HN, Bakris GL, Clark and atherothrombosis. N Engl J Med DB, Pasternak RC, Smith SC Jr, Stone NJ, NG, Costa F, Eckel R, Fonseca V, Ger- 2007;357:2482–2494 National Heart, Lung, and Blood Institute, stein HC, Grundy S, Nesto RW, Pignone 244. Watala C, Golanski J, Pluta J, Boncler M, American College of Cardiology Founda- MP, Plutzky J, Porte D, Redberg R, Stit- Rozalski M, Luzak B, Kropiwnicka A, tion, American Heart Association. Impli- zel KF, Stone NJ, American Heart Asso- Drzewoski J. Reduced sensitivity of cations of recent clinical trials for the ciation, American Diabetes Association. platelets from type 2 diabetic patients to National Cholesterol Education Program Primary prevention of cardiovascular acetylsalicylic acid (aspirin)-its relation Adult Treatment Panel III guidelines. Cir- diseases in people with diabetes melli- to metabolic control. Thromb Res 2004; culation 2004;110:227–239 tus: a scientific statement from the 113:101–113228. Chasman DI, Posada D, Subrahmanyan American Heart Association and the 245. Lev EI. Aspirin resistance transient lab- L, Cook NR, Stanton VP, Jr, Ridker PM. American Diabetes Association. Diabe- oratory finding or important clinical en- Pharmacogenetic study of statin therapy tes Care 2007;30:162–172 tity? J Am Coll Cardiol 2009;53:678 – and cholesterol reduction. JAMA 2004; 236. Antithrombotic Trialists’ (ATT) Collab- 680 291:2821–2827 oration, Baigent C, Blackwell L, Collins 246. Santilli F, Rocca B, De Cristofaro R, Lat-229. Baigent C, Keech A, Kearney PM, Black- R, Emberson J, Godwin J, Peto R, Buring tanzio S, Pietrangelo L, Habib A, Petti- well L, Buck G, Pollicino C, Kirby A, J, Hennekens C, Kearney P, Meade T, nella C, Recchiuti A, Ferrante E, Sourjina T, Peto R, Collins R, Simes R, Patrono C, Roncaglioni MC, Zanchetti Ciabattoni G, Davì G, Patrono C. Platelet Cholesterol Treatment Trialists’ (CTT) A. Aspirin in the primary and secondary cyclooxygenase inhibition by low-dose Collaborators. Efficacy and safety of prevention of vascular disease: collabo- aspirin is not reflected consistently by cholesterol-lowering treatment: pro- rative meta-analysis of individual partic- platelet function assays: implications for spective meta-analysis of data from ipant data from randomised trials. aspirin “resistance”. J Am Coll Cardiol 90,056 participants in 14 randomised Lancet 2009;373:1849 –1860 2009;53:667– 677 trials of statins. Lancet 2005;366:1267– 237. Wolff T, Miller T, Ko S. Aspirin for the 247. Bhatt DL, Marso SP, Hirsch AT, Ringleb 1278 primary prevention of cardiovascular PA, Hacke W, Topol EJ. Amplified ben-230. Elam MB, Hunninghake DB, Davis KB, events: an update of the evidence for the efit of clopidogrel versus aspirin in pa- Garg R, Johnson C, Egan D, Kostis JB, U.S. Preventive Services Task Force. tients with diabetes mellitus. Am J Sheps DS, Brinton EA. Effect of niacin on Ann Intern Med 2009;150:405– 410 Cardiol 2002;90:625– 628 lipid and lipoprotein levels and glycemic 238. US Preventive Services Task Force: As- 248. Haire-Joshu D, Glasgow RE, Tibbs TL. control in patients with diabetes and pe- pirin for the prevention of cardiovascu- Smoking and diabetes. Diabetes Care ripheral arterial disease: the ADMIT lar disease: U.S. Preventive Services Task 1999;22:1887–1898S56 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement249. American Diabetes Asociation: Smoking cet 2008;372:1174 –1183 2 diabetes. N Engl J Med 2001;345:851– and diabetes (Position Statement). Dia- 259. Garg JP, Bakris GL. Microalbuminuria: 860 betes Care 2004;27(Suppl. 1):S74 –S75 marker of vascular dysfunction, risk fac- 270. Brenner BM, Cooper ME, de Zeeuw D,250. US Preventive Services Task Force. tor for cardiovascular disease. Vasc Med Keane WF, Mitch WE, Parving HH, Re- Counseling to Prevent Tobacco Use and To- 2002;7:35– 43 muzzi G, Snapinn SM, Zhang Z, Shahin- bacco-Related Diseases: Recommendation 260. Klausen K, Borch-Johnsen K, Feldt-Ras- far S, RENAAL Study Investigators. Statement. Rockville, MD, Agency for mussen B, Jensen G, Clausen P, Effects of losartan on renal and cardio- Healthcare Research and Quality, 2003 Scharling H, Appleyard M, Jensen JS. vascular outcomes in patients with type251. Ranney L, Melvin C, Lux L, McClain E, Very low levels of microalbuminuria are 2 diabetes and nephropathy. N Engl Lohr KN. Systematic review: smoking associated with increased risk of coro- J Med 2001;345:861– 869 cessation intervention strategies for nary heart disease and death indepen- 271. Parving HH, Lehnert H, Brochner- ¨ adults and adults in special populations. dently of renal function, hypertension, Mortensen J, Gomis R, Andersen S, Ann Intern Med 2006;145:845– 856 and diabetes. Circulation 2004;110: Arner P, Irbesartan in Patients with Type252. Scognamiglio R, Negut C, Ramondo A, 32–35 2 Diabetes and Microalbuminuria Study Tiengo A, Avogaro A. Detection of coro- 261. Gall MA, Hougaard P, Borch-Johnsen K, Group. The effect of irbesartan on the nary artery disease in asymptomatic pa- Parving HH. Risk factors for develop- development of diabetic nephropathy in tients with type 2 diabetes mellitus. J Am ment of incipient and overt diabetic ne- patients with type 2 diabetes. N Engl Coll Cardiol 2006;47:65–71 phropathy in patients with non-insulin J Med 2001;345:870 – 878253. Boden WE, O’Rourke RA, Teo KK, Har- dependent diabetes mellitus: prospec- 272. Pepine CJ, Handberg EM, Cooper-De- tigan PM, Maron DJ, Kostuk WJ, Knudt- tive, observational study. BMJ 1997;314: Hoff RM, Marks RG, Kowey P, Messerli son M, Dada M, Casperson P, Harris CL, 783–788 FH, Mancia G, Cangiano JL, Garcia-Bar- Chaitman BR, Shaw L, Gosselin G, 262. Ravid M, Lang R, Rachmani R, Lishner reto D, Keltai M, Erdine S, Bristol HA, Nawaz S, Title LM, Gau G, Blaustein AS, M. Long-term renoprotective effect of Kolb HR, Bakris GL, Cohen JD, Parmley Booth DC, Bates ER, Spertus JA, Berman angiotensin-converting enzyme inhibi- WW, INVEST Investigators. A calcium DS, Mancini GB, Weintraub WS, tion in non-insulin-dependent diabetes antagonist vs a non-calcium antagonist COURAGE Trial Research Group. Opti- mellitus. A 7-year follow-up study. Arch hypertension treatment strategy for pa- mal medical therapy with or without PCI Intern Med 1996;156:286 –289 tients with coronary artery disease: the for stable coronary disease. N Engl J Med 263. Reichard P, Nilsson BY, Rosenqvist U. The International Verapamil-Trandolapril 2007;356:1503–1516 effect of long-term intensified insulin study (INVEST): a randomized con-254. BARI 2D Study Group, Frye RL, August treatment on the development of micro- trolled trial. JAMA 2003;290:2805– P, Brooks MM, Hardison RM, Kelsey SF, vascular complications of diabetes melli- 2816 MacGregor JM, Orchard TJ, Chaitman tus. N Engl J Med 1993;329:304 –309 273. Bakris GL, Siomos M, Richardson D, BR, Genuth SM, Goldberg SH, Hlatky 264. Effect of intensive therapy on the devel- Janssen I, Bolton WK, Hebert L, Agarwal MA, Jones TL, Molitch ME, Nesto RW, opment and progression of diabetic ne- R, Catanzaro D. ACE inhibition or an- Sako EY, Sobel BE. A randomized trial of phropathy in the Diabetes Control and giotensin receptor blockade: impact on therapies for type 2 diabetes and coro- Complications Trial. The Diabetes Con- potassium in renal failure. VAL-K Study nary artery disease. N Engl J Med 2009; trol and Complications (DCCT) Re- Group. Kidney Int 2000;58:2084 –2092 360:2503–2515 search Group. Kidney Int 1995;47: 274. Mogensen CE, Neldam S, Tikkanen I,255. Wackers FJ, Chyun DA, Young LH, 1703–1720 Oren S, Viskoper R, Watts RW, Cooper Heller GV, Iskandrian AE, Davey JA, 265. Lewis EJ, Hunsicker LG, Bain RP, Rohde ME. Randomised controlled trial of dual Barrett EJ, Taillefer R, Wittlin SD, Filip- RD. The effect of angiotensin-convert- blockade of renin-angiotensin system in chuk N, Ratner RE, Inzucchi SE: Reso- ing-enzyme inhibition on diabetic ne- patients with hypertension, microalbu- lution of asymptomatic myocardial phropathy. The Collaborative Study minuria, and non-insulin dependent di- ischemia in patients with type 2 diabetes Group. N Engl J Med 1993;329:1456 – abetes: the candesartan and lisinopril mellitus in the DIAD Study. Diabetes 1462 microalbuminuria (CALM) study. BMJ Care 2007;30:2892–2898 266. Remuzzi G, Macia M, Ruggenenti P. Pre- 2000;321:1440 –1444256. Young LH, Wackers FJ, Chyun DA, vention and treatment of diabetic renal 275. Schjoedt KJ, Jacobsen P, Rossing K, Davey JA, Barrett EJ, Taillefer R, Heller disease in type 2 diabetes: the BENE- Boomsma F, Parving HH. Dual blockade GV, Iskandrian AE, Wittlin SD, Filip- DICT study. JAmSocNephrol 2006;17: of the renin-angiotensin-aldosterone chuk N, Ratner RE, Inzucchi SE, DIAD S90 –S97 system in diabetic nephropathy: the role Investigators. Cardiac outcomes after 267. Bilous R, Chaturvedi N, Sjølie AK, Fuller of aldosterone. Horm Metab Res 2005; screening for asymptomatic coronary ar- J, Klein R, Orchard T, Porta M, Parving 37(Suppl. 1):4 – 8 tery disease in patients with type 2 dia- HH. Effect of candesartan on microalbu- 276. Schjoedt KJ, Rossing K, Juhl TR, betes: the DIAD study: a randomized minuria and albumin excretion rate in Boomsma F, Rossing P, Tarnow L, Parv- controlled trial. JAMA 2009;301:1547– diabetes: three randomized trials. Ann ing HH. Beneficial impact of spironolac- 1555 Intern Med 2009;151:11–14 tone in diabetic nephropathy. Kidney257. Braunwald E, Domanski MJ, Fowler SE, 268. Mauer M, Zinman B, Gardiner R, Suissa Int 2005;68:2829 –2836 Geller NL, Gersh BJ, Hsia J, Pfeffer MA, S, Sinaiko A, Strand T, Drummond K, 277. Parving HH, Persson F, Lewis JB, Lewis Rice MM, Rosenberg YD, Rouleau JL, Donnelly S, Goodyer P, Gubler MC, EJ, Hollenberg NK, AVOID Study Inves- PEACE Trial Investigators. Angiotensin- Klein R. Renal and retinal effects of ena- tigators. Aliskiren combined with losar- converting-enzyme inhibition in stable lapril and losartan in type 1 diabetes. tan in type 2 diabetes and nephropathy. coronary artery disease. N Engl J Med N Engl J Med 2009;361:40 –51 N Engl J Med 2008;358:2433–2446 2004;351:2058 –2068 269. Lewis EJ, Hunsicker LG, Clarke WR, 278. Pijls LT, de Vries H, Donker AJ, van Eijk258. Effects of the angiotensin-receptor Berl T, Pohl MA, Lewis JB, Ritz E, Atkins JT. The effect of protein restriction on blocker telmisartan on cardiovascular RC, Rohde R, Raz I, Collaborative Study albuminuria in patients with type 2 dia- events in high-risk patients intolerant to Group. Renoprotective effect of the an- betes mellitus: a randomized trial. angiotensin-converting enzyme inhibi- giotensin-receptor antagonist irbesartan Nephrol Dial Transplant 1999;14:1445– tors: a randomised controlled trial. Lan- in patients with nephropathy due to type 1453care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S57
    • Standards of Medical Care279. Pedrini MT, Levey AS, Lau J, Chalmers ment). Diabetes Care 2004;27(Suppl. 304. American Diabetes Association: Reti- TC, Wang PH. The effect of dietary pro- 1):S79 –S83 nopathy in diabetes. Diabetes Care tein restriction on the progression of di- 291. Klein R. Hyperglycemia and microvas- 2004;27 Suppl. 1:S84 –S87 abetic and nondiabetic renal diseases: a cular and macrovascular disease in dia- 305. Ciulla TA, Amador AG, Zinman B. Dia- meta-analysis. Ann Intern Med 1996; betes. Diabetes Care 1995;18:258 –268 betic retinopathy and diabetic macular 124:627– 632 292. Estacio RO, McFarling E, Biggerstaff S, edema: pathophysiology, screening, and280. Hansen HP, Tauber-Lassen E, Jensen Jeffers BW, Johnson D, Schrier RW. novel therapies. Diabetes Care 2003;26: BR, Parving HH. Effect of dietary protein Overt albuminuria predicts diabetic ret- 2653–2664 restriction on prognosis in patients with inopathy in Hispanics with NIDDM. 306. Boulton AJ, Vinik AI, Arezzo JC, Bril V, diabetic nephropathy. Kidney Int 2002; Am J Kidney Dis 1998;31:947–953 Feldman EL, Freeman R, Malik RA, Ma- 62:220 –228 293. Leske MC, Wu SY, Hennis A, Hyman L, ser RE, Sosenko JM, Ziegler D, American281. Kasiske BL, Lakatua JD, Ma JZ, Louis TA. Nemesure B, Yang L, Schachat AP, Bar- Diabetes Association. Diabetic neuropa- A meta-analysis of the effects of dietary bados Eye Study Group. Hyperglycemia, thies: a statement by the American Dia- protein restriction on the rate of decline blood pressure, and the 9-year incidence betes Association. Diabetes Care 2005; in renal function. Am J Kidney Dis 1998; of diabetic retinopathy: the Barbados 28:956 –962 31:954 –961 Eye Studies. Ophthalmology 2005;112: 307. Vinik AI, Maser RE, Mitchell BD, Free-282. Eknoyan G, Hostetter T, Bakris GL, He- 799 – 805 man R. Diabetic autonomic neuropathy. bert L, Levey AS, Parving HH, Steffes 294. Fong DS, Aiello LP, Ferris FL 3rd, Klein Diabetes Care 2003;26:1553–1579 MW, Toto R. Proteinuria and other R. Diabetic retinopathy. Diabetes Care 308. Boulton AJ, Armstrong DG, Albert SF, markers of chronic kidney disease: a po- 2004;27:2540 –2553 Frykberg RG, Hellman R, Kirkman MS, sition statement of the national kidney 295. Diabetes Control and Complications Lavery LA, Lemaster JW, Mills JL Sr, foundation (NKF) and the national insti- Trial Research Group: Effect of preg- Mueller MJ, Sheehan P, Wukich DK, tute of diabetes and digestive and kidney nancy on microvascular complications American Diabetes Association, Ameri- diseases (NIDDK). Am J Kidney Dis in the diabetes control and complica- can Association of Clinical Endocrinolo- 2003;42:617– 622 tions trial. The Diabetes Control and gists. Comprehensive foot examination283. Levey AS, Coresh J, Balk E, Kausz AT, Complications Trial Research Group. and risk assessment: a report of the task Levin A, Steffes MW, Hogg RJ, Perrone Diabetes Care 2000;23:1084 –1091 force of the foot care interest group of RD, Lau J, Eknoyan G, National Kidney 296. The Diabetic Retinopathy Study (DRS) the American Diabetes Association, with Foundation. National Kidney Founda- Research Group. Preliminary report on endorsement by the American Associa- tion practice guidelines for chronic kid- the effects of photocoagulation therapy: tion of Clinical Endocrinologists. Diabe- ney disease: evaluation, classification, DRS Report #1. Am J Ophthalmol 1976; tes Care 2008;31:1679 –1685 and stratification. Ann Intern Med 2003; 81:383–396. 309. American Diabetes Association: Periph- 139:137–147 297. Photocoagulation for diabetic macular eral arterial disease in people with dia-284. Kramer H, Molitch ME. Screening for edema. Early Treatment Diabetic Reti- betes (Consensus Statement). Diabetes kidney disease in adults with diabetes. nopathy Study report number 1. Early Care 2003;26:3333–3341 Diabetes Care 2005;28:1813–1816 Treatment Diabetic Retinopathy Study 310. American Diabetes Association: Consen-285. Kramer HJ, Nguyen QD, Curhan G, Hsu research group. Arch Ophthalmol 1985; sus Development Conference on Dia- CY. Renal insufficiency in the absence of 103:1796 –1806 betic Foot Wound Care, 7– 8 April albuminuria and retinopathy among 298. Klein R, Klein BE, Moss SE, Davis MD, 1999, Boston, Massachusetts. Diabetes adults with type 2 diabetes mellitus. DeMets DL. The Wisconsin epidemiologic Care 1999;22:1354 –1360 JAMA 2003;289:3273–3277 study of diabetic retinopathy. II. Preva- 311. Silverstein J, Klingensmith G, Copeland286. Tsalamandris C, Allen TJ, Gilbert RE, lence and risk of diabetic retinopathy KC, Plotnick L, Kaufman F, Laffel L, Sinha A, Panagiotopoulos S, Cooper ME, when age at diagnosis is less than 30 years. Deeb LC, Grey M, Anderson BJ, Hol- Jerums G. Progressive decline in renal Arch Ophthalmol 1984;102:520 –526 zmeister LA, and Clark NG Care of chil- function in diabetic patients with and 299. Harris MI, Klein R, Welborn TA, dren and adolescents with type 1 without albuminuria. Diabetes 1994;43: Knuiman MW. Onset of NIDDM occurs diabetes mellitus: A statement of the 649 – 655 at least 4 –7 yr before clinical diagnosis. American Diabetes Association. Diabe-287. Levey AS, Bosch JP, Lewis JB, Greene T, Diabetes Care 1992;15:815– 819 tes Care 2005; 28:186 –212. Rogers N, Roth D. A more accurate 300. Vijan S, Hofer TP, Hayward RA. Cost- 312. Northam EA, Anderson PJ, Werther GA, method to estimate glomerular filtration utility analysis of screening intervals for Warne GL, Adler RG, Andrewes D. Neu- rate from serum creatinine: a new pre- diabetic retinopathy in patients with ropsychological complications of IDDM diction equation. Modification of Diet in type 2 diabetes mellitus. JAMA 2000; in children 2 years after disease onset. Renal Disease Study Group. Ann Intern 283:889 – 896 Diabetes Care 1998;21:379 –384 Med 1999;130:461– 470 301. Klein R. Screening interval for retinopa- 313. Rovet J, Alvarez M. Attentional function-288. Rigalleau V, Lasseur C, Perlemoine C, thy in type 2 diabetes. Lancet 2003;361: ing in children and adolescents with Barthe N, Raffaitin C, Liu C, Chauveau 190 –191 IDDM. Diabetes Care 1997;20:803– 810 P, Baillet-Blanco L, Beauvieux MC, 302. Younis N, Broadbent DM, Vora JP, Har- 314. Bjørgaas M, Gimse R, Vik T, Sand T. Combe C, Gin H. Estimation of glomer- ding SP, Liverpool Diabetic Eye Study. Cognitive function in type 1 diabetic ular filtration rate in diabetic subjects: Incidence of sight-threatening retinopa- children with and without episodes of Cockcroft formula or modification of thy in patients with type 2 diabetes in the severe hypoglycaemia. Acta Paediatr Diet in Renal Disease study equation? Liverpool Diabetic Eye Study: a cohort 1997;86:148 –153 Diabetes Care 2005;28:838 – 843 study. Lancet 2003;361:195–200 315. Doyle EA, Weinzimer SA, Steffen AT,289. Levinsky NG. Specialist evaluation in 303. Ahmed J, Ward TP, Bursell SE, Aiello Ahern JA, Vincent M, Tamborlane WV. chronic kidney disease: too little, too LM, Cavallerano JD, Vigersky RA. The A randomized, prospective trial compar- late. Ann Intern Med 2002;137:542– sensitivity and specificity of nonmydri- ing the efficacy of continuous subcuta- 543 atic digital stereoscopic retinal imaging neous insulin infusion with multiple290. American Diabetes Association: Ne- in detecting diabetic retinopathy. Diabe- daily injections using insulin glargine. phropathy in diabetes (Position State- tes Care 2006;29:2205–2209 Diabetes Care 2004;27:1554 –1558S58 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement316. Nimri R, Weintrob N, Benzaquen H, Hypertension, and Obesity in Youth in children and adolescents with Type 1 Ofan R, Fayman G, Phillip M. Insulin Committee, American Heart Association diabetes. Diabet Med 2002;19:518 –521 pump therapy in youth with type 1 dia- Council of Cardiovascular Disease in the 332. Mohn A, Di Michele S, Di Luzio R, betes: a retrospective paired study. Pedi- Young, American Heart Association Tumini S, Chiarelli F. The effect of sub- atrics 2006;117:2126 –2131 Council on Cardiovascular Nursing. clinical hypothyroidism on metabolic317. Krantz JS, Mack WJ, Hodis HN, Liu CR, Drug therapy of high-risk lipid abnor- control in children and adolescents with Liu CH, Kaufman FR. Early onset of sub- malities in children and adolescents: a Type 1 diabetes mellitus. Diabet Med clinical atherosclerosis in young persons scientific statement from the American 2002;19:70 –73 with type 1 diabetes. J Pediatr 2004;145: Heart Association Atherosclerosis, Hy- 333. Chase HP, Garg SK, Cockerham RS, 452– 457 pertension, and Obesity in Youth Com- Wilcox WD, Walravens PA. Thyroid318. Jarvisalo MJ, Putto-Laurila A, Jartti L, ¨ mittee, Council of Cardiovascular hormone replacement and growth of Lehtimaki T, Solakivi T, Ronnemaa T, ¨ ¨ Disease in the Young, with the Council children with subclinical hypothyroid- Raitakari OT. Carotid artery intima-me- on Cardiovascular Nursing. Circulation ism and diabetes. Diabet Med 1990;7: dia thickness in children with type 1 di- 2007;115:1948 –1967 299 –303 abetes. Diabetes 2002;51:493– 498 323. Salo P, Viikari J, Hamalainen M, Lapin- ¨ ¨ ¨ 334. Eppens MC, Craig ME, Cusumano J,319. Haller MJ, Samyn M, Nichols WW, leimu H, Routi T, Ronnemaa T, Sep- ¨ Hing S, Chan AK, Howard NJ, Silink M, Brusko T, Wasserfall C, Schwartz RF, At- panen R, Jokinen E, Valimaki I, Simell ¨ ¨ ¨ Donaghue KC. Prevalence of diabetes kinson M, Shuster JJ, Pierce GL, Silver- O. Serum cholesterol ester fatty acids in complications in adolescents with type 2 stein JH. Radial artery tonometry 7- and 13-month-old children in a pro- compared with type 1 diabetes. Diabetes demonstrates arterial stiffness in chil- spective randomized trial of a low-satu- Care 2006;29:1300 –1306 dren with type 1 diabetes. Diabetes Care rated fat, low-cholesterol diet: the STRIP 335. Kitzmiller JL, Gavin LA, Gin GD, Jo- 2004;27:2911–2917 baby project. Special Turku coronary vanovic-Peterson L, Main EK, Zigrang320. Orchard TJ, Forrest KY, Kuller LH, Risk factor Intervention Project for chil- WD. Preconception care of diabetes. Becker DJ, Pittsburgh Epidemiology of dren. Acta Paediatr 1999;88:505–512 Glycemic control prevents congenital Diabetes Complications Study. Lipid 324. Efficacy and safety of lowering dietary anomalies. JAMA 1991;265:731–736 and blood pressure treatment goals for intake of fat and cholesterol in children 336. Goldman JA, Dicker D, Feldberg D, Ye- type 1 diabetes: 10-year incidence data with elevated low-density lipoprotein shaya A, Samuel N, Karp M. Pregnancy from the Pittsburgh Epidemiology of Di- cholesterol. The Dietary Intervention outcome in patients with insulin-depen- abetes Complications Study. Diabetes Study in Children (DISC). The Writing dent diabetes mellitus with preconcep- Care 2001;24:1053–1059 Group for the DISC Collaborative Re- tional diabetic control: a comparative321. Kavey RE, Allada V, Daniels SR, Hayman search Group. JAMA 1995;273:1429 – study. AmJ Obstet Gynecol 1986;155: LL, McCrindle BW, Newburger JW, 1435 293–297 Parekh RS, Steinberger J, American 325. McCrindle BW, Ose L, Marais AD. Effi- 337. Rosenn B, Miodovnik M, Combs CA, Heart Association Expert Panel on Pop- cacy and safety of atorvastatin in chil- Khoury J, Siddiqi TA. Pre-conception ulation and Prevention Science, Ameri- dren and adolescents with familial management of insulin-dependent dia- can Heart Association Council on hypercholesterolemia or severe hyper- betes: improvement of pregnancy out- Cardiovascular Disease in the Young, lipidemia: a multicenter, randomized, come. Obstet Gynecol 1991;77:846 – American Heart Association Council on placebo-controlled trial. J Pediatr 2003; 849 Epidemiology and Prevention, Ameri- 143:74 – 80 338. Tchobroutsky C, Vray MM, Altman JJ. can Heart Association Council on Nutri- 326. de Jongh S, Lilien MR, op’t RJ, Stroes ES, Risk/benefit ratio of changing late ob- tion, Physical Activity and Metabolism, Bakker HD, Kastelein JJ. Early statin stetrical strategies in the management of American Heart Association Council on therapy restores endothelial function in insulin-dependent diabetic pregnancies. High Blood Pressure Research, Ameri- children with familial hypercholesterol- A comparison between 1971–1977 and can Heart Association Council on Car- emia. J Am Coll Cardiol 2002;40:2117– 1978 –1985 periods in 389 pregnancies. diovascular Nursing, American Heart 2121 Diabete Metab 1991;17:287–294 Association Council on the Kidney in 327. Wiegman A, Hutten BA, de Groot E, Ro- 339. Willhoite MB, Bennert HW, Jr, Palomaki Heart Disease, Interdisciplinary Work- denburg J, Bakker HD, Buller HR, Si- ¨ GE, Zaremba MM, Herman WH, Wil- ing Group on Quality of Care and Out- jbrands EJ, Kastelein JJ. Efficacy and liams JR, Spear NH. The impact of pre- comes Research. Cardiovascular risk safety of statin therapy in children with conception counseling on pregnancy reduction in high-risk pediatric patients: familial hypercholesterolemia: a ran- outcomes. The experience of the Maine a scientific statement from the American domized controlled trial. JAMA 2004; Diabetes in Pregnancy Program. Diabe- Heart Association Expert Panel on Pop- 292:331–337 tes Care 1993;16:450 – 455 ulation and Prevention Science; the 328. Holmes GK. Screening for coeliac dis- 340. Cooper WO, Hernandez-Diaz S, Arbo- Councils on Cardiovascular Disease in ease in type 1 diabetes. Arch Dis Child gast PG, Dudley JA, Dyer S, Gideon PS, the Young, Epidemiology and Preven- 2002;87:495– 498 Hall K, Ray WA. Major congenital mal- tion, Nutrition, Physical Activity and 329. Rewers M, Liu E, Simmons J, Redondo formations after first-trimester exposure Metabolism, High Blood Pressure Re- MJ, Hoffenberg EJ: Celiac disease asso- to ACE inhibitors. N Engl J Med 2006; search, Cardiovascular Nursing, and the ciated with type 1 diabetes mellitus. En- 354:2443–2451 Kidney in Heart Disease; and the Inter- docrinol Metab Clin North Am 2004;33: 341. American Diabetes Association: Precon- disciplinary Working Group on Quality 197–214, xi ception care of women with diabetes of Care and Outcomes Research: en- 330. Roldan MB, Alonso M, Barrio R. Thyroid (Position Statement). Diabetes Care dorsed by the American Academy of Pe- autoimmunity in children and adoles- 2004;27(Suppl. 1):S76 –S78 diatrics. Circulation 2006;114:2710 – cents with Type 1 diabetes mellitus. Di- 342. Brown AF, Mangione CM, Saliba D, 2738 abetes Nutr Metab 1999;12:27–31 Sarkisian CA, California Healthcare322. McCrindle BW, Urbina EM, Dennison 331. Kordonouri O, Deiss D, Danne T, Foundation/American Geriatrics Society BA, Jacobson MS, Steinberger J, Roc- Dorow A, Bassir C, Gruters-Kieslich A. ¨ Panel on Improving Care for Elders with chini AP, Hayman LL, Daniels SR, Amer- Predictivity of thyroid autoantibodies Diabetes. Guidelines for improving the ican Heart Association Atherosclerosis, for the development of thyroid disorders care of the older person with diabetescare.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S59
    • Standards of Medical Care mellitus. J Am Geriatr Soc 2003;51: betes mellitus and acute myocardial in- 32:591–595 S265–S280 farction: long-term results from the 363. Donihi AC, Raval D, Saul M, Koryt-343. Curb JD, Pressel SL, Cutler JA, Savage Diabetes and Insulin-Glucose Infusion in kowski MT, DeVita MA. Prevalence and PJ, Applegate WB, Black H, Camel G, Acute Myocardial Infarction (DIGAMI) predictors of corticosteroid-related hy- Davis BR, Frost PH, Gonzalez N, Guthrie study. Circulation 1999;99:2626 –2632 perglycemia in hospitalized patients. G, Oberman A, Rutan GH, Stamler J. Ef- 353. Wiener RS, Wiener DC, Larson RJ. Ben- Endocr Pract 2006;12:358 –362 fect of diuretic-based antihypertensive efits and risks of tight glucose control in 364. Goldberg PA, Siegel MD, Sherwin RS, treatment on cardiovascular disease risk critically ill adults: a meta-analysis. Halickman JI, Lee M, Bailey VA, Lee SL, in older diabetic patients with isolated JAMA 2008;300:933–944 Dziura JD, Inzucchi SE. Implementation systolic hypertension. Systolic Hyper- 354. Brunkhorst FM, Engel C, Bloos F, Meier- of a safe and effective insulin infusion tension in the Elderly Program Cooper- Hellmann A, Ragaller M, Weiler N, Mo- protocol in a medical intensive care unit. ative Research Group. JAMA 1996;276: erer O, Gruendling M, Oppert M, Grond Diabetes Care 2004;27:461– 467 1886 –1892 S, Olthoff D, Jaschinski U, John S, Ros- 365. Rea RS, Donihi AC, Bobeck M, Herout P,344. Beckett NS, Peters R, Fletcher AE, Staes- saint R, Welte T, Schaefer M, Kern P, McKaveney TP, Kane-Gill SL, Koryt- sen JA, Liu L, Dumitrascu D, Stoyanovsky Kuhnt E, Kiehntopf M, Hartog C, Natan- kowski MT. Implementing an intrave- V, Antikainen RL, Nikitin Y, Anderson C, son C, Loeffler M, Reinhart K, German nous insulin infusion protocol in the Belhani A, Forette F, Rajkumar C, Thijs L, Competence Network Sepsis (SepNet). intensive care unit. Am J Health Syst Banya W, Bulpitt CJ, HYVET Study Intensive insulin therapy and pen- Pharm 2007;64:385–395 Group. Treatment of hypertension in pa- tastarch resuscitation in severe sepsis. 366. Nazer LH, Chow SL, Moghissi ES. Insu- tients 80 years of age or older. N Engl N Engl J Med 2008;358:125–139 lin infusion protocols for critically ill pa- J Med 2008;358:1887–1898 355. NICE-SUGAR Study Investigators, Fin- tients: a highlight of differences and345. Clement S, Braithwaite SS, Magee MF, fer S, Chittock DR, Su SY, Blair D, Foster similarities. Endocr Pract 2007;13:137– Ahmann A, Smith EP, Schafer RG, Hir- D, Dhingra V, Bellomo R, Cook D, 146 sch IB, Hirsh IB, American Diabetes As- Dodek P, Henderson WR, Hebert PC, ´ 367. DeSantis AJ, Schmeltz LR, Schmidt K, sociation Diabetes in Hospitals Writing Heritier S, Heyland DK, McArthur C, O’Shea-Mahler E, Rhee C, Wells A, Committee. Management of diabetes McDonald E, Mitchell I, Myburgh JA, Brandt S, Peterson S, Molitch ME. Inpa- and hyperglycemia in hospitals. Diabe- Norton R, Potter J, Robinson BG, Ronco tient management of hyperglycemia: the tes Care 2004;27:553–591 JJ. Intensive versus conventional glucose Northwestern experience. Endocr Pract346. Moghissi ES, Korytkowski MT, DiNardo control in critically ill patients. N Engl 2006;12:491–505 M, Einhorn D, Hellman R, Hirsch IB, In- J Med 2009;360:1283–1297 368. Noschese M, Donihi AC, Koerbel G, zucchi SE, Ismail-Beigi F, Kirkman MS, 356. Krinsley JS, Grover A. Severe hypoglyce- Karslioglu E, DiNardo M, Curll M, Ko- Umpierrez GE, American Association of mia in critically ill patients: risk factors rytkowski MT. Effect of a diabetes order Clinical Endocrinologists, American and outcomes. Crit Care Med 2007;35: set on glycaemic management and con- Diabetes Association. American Asso- 2262–2267 trol in the hospital. Qual Saf Health Care ciation of Clinical Endocrinologists 357. Van den Berghe G, Wilmer A, Hermans 2008;17:464 – 468 and American Diabetes Association G, Meersseman W, Wouters PJ, Milants 369. Umpierrez GE, Hor T, Smiley D, Tem- consensus statement on inpatient gly- I, Van Wijngaerden E, Bobbaers H, poni A, Umpierrez D, Ceron M, Munoz cemic control. Diabetes Care 2009;32: Bouillon R. Intensive insulin therapy in C, Newton C, Peng L, Baldwin D. Com- 1119 –1131 the medical ICU. N Engl J Med 2006; parison of inpatient insulin regimens347. American Diabetes Association: Eco- 354:449 – 461 with detemir plus aspart versus neutral nomic costs of diabetes in the U.S. In 358. Griesdale DE, de Souza RJ, van Dam RM, protamine hagedorn plus regular in 2007. Diabetes Care 2008;31:596 – 615 Heyland DK, Cook DJ, Malhotra A, medical patients with type 2 diabetes.348. Centers for Disease Control and Preven- Dhaliwal R, Henderson WR, Chittock J Clin Endocrinol Metab 2009;94:564 – tion. National Diabetes Fact Sheet: Gen- DR, Finfer S, Talmor D. Intensive insulin 569 eral Information and National Estimates on therapy and mortality among critically 370. Moghissi ES, Hirsch IB. Hospital man- Diabetes in the United States, 2007. At- ill patients: a meta-analysis including agement of diabetes. Endocrinol Metab lanta, GA, US Department of Health and NICE-SUGAR study data. CMAJ 2009; Clin North Am 2005;34:99 –116 Human Services, 2008 180:821– 827 371. Umpierrez GE, Smiley D, Zisman A, Pri-349. Levetan CS, Passaro M, Jablonski K, Kass 359. Saudek CD, Herman WH, Sacks DB, eto LM, Palacio A, Ceron M, Puig A, Me- M, Ratner RE. Unrecognized diabetes Bergenstal RM, Edelman D, Davidson jia R. Randomized study of basal-bolus among hospitalized patients. Diabetes MB. A new look at screening and diag- insulin therapy in the inpatient manage- Care 1998;21:246 –249 nosing diabetes mellitus. J Clin Endocri- ment of patients with type 2 diabetes350. Umpierrez GE, Isaacs SD, Bazargan N, nol Metab 2008;93:2447–2453 (RABBIT 2 trial). Diabetes Care 2007;30: You X, Thaler LM, Kitabchi AE. Hyper- 360. Mitrakou A, Ryan C, Veneman T, Mokan 2181–2186 glycemia: an independent marker of in- M, Jenssen T, Kiss I, Durrant J, Cryer P, 372. Umpierrez GE, Palacio A, Smiley D. hospital mortality in patients with Gerich J. Hierarchy of glycemic thresholds Sliding scale insulin use: myth or insan- undiagnosed diabetes. J Clin Endocrinol for counterregulatory hormone secretion, ity? Am J Med 2007;120:563–567 Metab 2002;87:978 –982 symptoms, and cerebral dysfunction. Am J 373. Queale WS, Seidler AJ, Brancati FL. Gly-351. van den Berghe G, Wouters P, Weekers Physiol 1991;260:E67–E74 cemic control and sliding scale insulin F, Verwaest C, Bruyninckx F, Schetz M, 361. Korytkowski M, DiNardo M, Donihi AC, use in medical inpatients with diabetes Vlasselaers D, Ferdinande P, Lauwers P, Bigi L, Devita M. Evolution of a diabetes mellitus. Arch Intern Med 1997;157: Bouillon R. Intensive insulin therapy in inpatient safety committee. Endocr Pract 545–552 the critically ill patients. N Engl J Med 2006;12(Suppl. 3):91–99 374. Korytkowski MT, Salata RJ, Koerbel GL, 2001;345:1359 –1367 362. DiNardo M, Noschese M, Korytkowski Selzer F, Karslioglu E, Idriss AM, Lee352. Malmberg K, Norhammar A, Wedel H, M, Freeman S. The medical emergency KK, Moser AJ, Toledo FG. Insulin ther- Ryden L. Glycometabolic state at admis- ´ team and rapid response system: find- apy and glycemic control in hospitalized sion: important risk marker of mortality in ing, treating, and preventing hypoglyce- patients with diabetes during enteral nu- conventionally treated patients with dia- mia. Jt Comm J Qual Patient Saf 2006; trition therapy: a randomized controlledS60 DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 care.diabetesjournals.org
    • Position Statement clinical trial. Diabetes Care 2009;32: 389. D’Orazio P, Burnett RW, Fogh- 1):124 –130 594 –596 Andersen N, Jacobs E, Kuwa K, Kulp- ¨ 400. Mahoney JJ. Reducing patient drug ac-375. Hirsch IB. Sliding scale insulin–time to mann WR, Larsson L, Lewenstam A, quisition costs can lower diabetes health stop sliding. JAMA 2009;301:213–214 Maas AH, Mager G, Naskalski JW, claims. Am J Manag Care 2005;11:376. Umpierrez GE. Basal versus sliding-scale Okorodudu AO, International Federa- S170 –S176 regular insulin in hospitalized patients tion of Clinical Chemistry Scientific Di- 401. Maney M, Tseng CL, Safford MM, Miller with hyperglycemia during enteral nu- vision Working Group on Selective DR, Pogach LM. Impact of self-reported trition therapy. Diabetes Care 2009;32: Electrodes and Point of Care Testing. patient characteristics upon assessment 751–753 Approved IFCC recommendation on re- of glycemic control in the Veterans377. Pancorbo-Hidalgo PL, García-Fernan- porting results for blood glucose (abbre- Health Administration. Diabetes Care dez FP, Ramírez-Perez C. Complications ´ viated). Clin Chem 2005;51:1573–1576 2007;30:245–251 associated with enteral nutrition by na- 390. Dungan K, Chapman J, Braithwaite SS, 402. Bergenstal RM. Treatment models from sogastric tube in an internal medicine Buse J. Glucose measurement: con- the International Diabetes Center: ad- unit. J Clin Nurs 2001;10:482– 490 founding issues in setting targets for in- vancing from oral agents to insulin ther-378. Nylen ES, Muller B. Endocrine changes patient management. Diabetes Care apy in type 2 diabetes. Endocr Pract in critical illness. J Intensive Care Med 2007;30:403– 409 2006;12(Suppl. 1):98 –104 2004;19:67– 82 391. Boyd JC, Bruns DE. Quality specifica- 403. Berikai P, Meyer PM, Kazlauskaite R,379. Shilo S, Berezovsky S, Friedlander Y, tions for glucose meters: assessment by Savoy B, Kozik K, Fogelfeld L. Gain in Sonnenblick M. Hypoglycemia in hospi- simulation modeling of errors in insulin patients’ knowledge of diabetes manage- talized nondiabetic older patients. J Am dose. Clin Chem 2001;47:209 –214 ment targets is associated with better Geriatr Soc 1998;46:978 –982 392. Goldberg PA, Siegel MD, Russell RR, Sh- glycemic control. Diabetes Care 2007;380. Fischer KF, Lees JA, Newman JH. Hypo- erwin RS, Halickman JI, Cooper DA, 30:1587–1589 glycemia in hospitalized patients. Dziura JD, Inzucchi SE. Experience with 404. O’Connor PJ. Electronic medical records Causes and outcomes. N Engl J Med the continuous glucose monitoring sys- and diabetes care improvement: are we 1986;315:1245–1250 tem in a medical intensive care unit. Di- waiting for Godot? Diabetes Care 2003;381. Markovitz LJ, Wiechmann RJ, Harris N, abetes Technol Ther 2004;6:339 –347 26:942–943 Hayden V, Cooper J, Johnson G, Harel- 393. Cheung BM, Ong KL, Cherny SS, Sham 405. Shojania KG, Ranji SR, McDonald KM, stad R, Calkins L, Braithwaite SS. De- PC, Tso AW, Lam KS. Diabetes preva- Grimshaw JM, Sundaram V, Rushakoff scription and evaluation of a glycemic lence and therapeutic target achieve- RJ, Owens DK. Effects of quality im- management protocol for patients with ment in the United States, 1999 to 2006. provement strategies for type 2 diabetes diabetes undergoing heart surgery. En- Am J Med 2009;122:443– 453 on glycemic control: a meta-regression docr Pract 2002;8:10 –18 394. Coleman K, Austin BT, Brach C, Wagner analysis. JAMA 2006;296:427– 440382. Levetan CS, Salas JR, Wilets IF, Zumoff EH. Evidence on the Chronic Care 406. Davidson MB. How our current medical B. Impact of endocrine and diabetes Model in the new millennium. Health care system fails people with diabetes: team consultation on hospital length of Aff (Millwood) 2009;28:75– 85 lack of timely, appropriate clinical deci- stay for patients with diabetes. Am J Med 395. Clark CM, Jr, Snyder JW, Meek RL, Stutz 1995;99:22–28 LM, Parkin CG. A systematic approach sions. Diabetes Care 2009;32:370 –372383. Levetan CS, Passaro MD, Jablonski KA, to risk stratification and intervention 407. McLean DL, McAlister FA, Johnson JA, Ratner RE. Effect of physician specialty within a managed care environment im- King KM, Makowsky MJ, Jones CA, on outcomes in diabetic ketoacidosis. proves diabetes outcomes and patient Tsuyuki RT, SCRIP-HTN Investigators. A Diabetes Care 1999;22:1790 –1795 satisfaction.DiabetesCare2001;24:1079 – randomized trial of the effect of commu-384. Koproski J, Pretto Z, Poretsky L. Effects 1086 nity pharmacist and nurse care on improv- of an intervention by a diabetes team in 396. Meigs JB, Cagliero E, Dubey A, Murphy- ing blood pressure management in hospitalized patients with diabetes. Dia- Sheehy P, Gildesgame C, Chueh H, patients with diabetes mellitus: study of betes Care 1997;20:1553–1555 Barry MJ, Singer DE, Nathan DM. A con- cardiovascular risk intervention by phar-385. Furnary AP, Braithwaite SS. Effects of trolled trial of web-based diabetes dis- macists-hypertension (SCRIP-HTN). Arch outcome on in-hospital transition from ease management: the MGH diabetes Intern Med 2008;168:2355–2361 intravenous insulin infusion to subcuta- primary care improvement project. Dia- 408. Parchman ML, Zeber JE, Romero RR, neous therapy. Am J Cardiol 2006;98: betes Care 2003;26:750 –757 Pugh JA. Risk of coronary artery disease 557–564 397. O’Connor PJ, Desai J, Solberg LI, Reger in type 2 diabetes and the delivery of386. American Diabetes Association: Diabe- LA, Crain AL, Asche SE, Pearson TL, care consistent with the chronic care tes nutrition recommendations for Clark CK, Rush WA, Cherney LM, model in primary care settings: a STAR- health care institutions (Position State- Sperl-Hillen JM, Bishop DB. Random- Net study. Med Care 2007;45:1129 – ment). Diabetes Care 2004;27(Suppl. ized trial of quality improvement inter- 1134 1):S55–S57 vention to improve diabetes care in 409. Feifer C, Nemeth L, Nietert PJ, Wessell387. Boucher JL, Swift CS, Franz MJ, primary care settings. Diabetes Care AM, Jenkins RG, Roylance L, Ornstein Kulkarni K, Schafer RG, Pritchett E, 2005;28:1890 –1897 SM. Different paths to high-quality care: Clark NG. Inpatient management of di- 398. Sperl-Hillen JM, O’Connor PJ. Factors three archetypes of top-performing abetes and hyperglycemia: implications driving diabetes care improvement in a practice sites. Ann Fam Med 2007;5: for nutrition practice and the food and large medical group: ten years of 233–241 nutrition professional. J Am Diet Assoc progress. Am J Manag Care 2005;11: 410. Ornstein S, Nietert PJ, Jenkins RG, Wes- 2007;107:105–111 S177–S185 sell AM, Nemeth LS, Feifer C, Corley388. Scott MG, Bruns DE, Boyd JC, Sacks DB. 399. Siminerio LM. Implementing diabetes ST. Improving diabetes care through a Tight glucose control in the intensive self-management training programs: multicomponent quality improvement care unit: are glucose meters up to the breaking through the barriers in pri- model in a practice-based research net- task? Clin Chem 2009;55:18 –20 mary care. EndocrPract 2006;12(Suppl. work. Am J Med Qual 2007;22:34 – 41care.diabetesjournals.org DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S61