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    Ada2011 Ada2011 Document Transcript

    • P O S I T I O N S T A T E M E N TStandards of Medical Care in Diabetes—2011AMERICAN DIABETES ASSOCIATIONCONTENTS 1. Hypertension/blood pressure 4. Diabetes care providers in the control hospitalI. CLASSIFICATION AND DIAGNOSIS 2. Dyslipidemia/lipid management 5. Self-management in the hospital OF DIABETES, p. S12 3. Antiplatelet agents 6. Diabetes self-management edu- A. Classification of diabetes 4. Smoking cessation cation in the hospital B. Diagnosis of diabetes 5. Coronary heart disease screen- 7. Medical nutrition therapy in the C. Categories of increased risk for di- ing and treatment hospital abetes (prediabetes) B. Nephropathy screening and treat- 8. Bedside blood glucose monitor-II. TESTING FOR DIABETES IN ASYMP- ment ing TOMATIC PATIENTS, p. S13 C. Retinopathy screening and treat- 9. Discharge planning A. Testing for type 2 diabetes and risk ment IX. STRATEGIES FOR IMPROVING DI- of future diabetes in adults D. Neuropathy screening and treat- ABETES CARE, p. S46 B. Testing for type 2 diabetes in chil- ment D dren iabetes is a chronic illness that re- E. Foot care C. Screening for type 1 diabetes quires continuing medical care and VII. DIABETES CARE IN SPECIFIC POP-III. DETECTION AND DIAGNOSIS OF ongoing patient self-management ULATIONS, p. S38 GESTATIONAL DIABETES MELLI- education and support to prevent acute A. Children and adolescents TUS, p. S15 complications and to reduce the risk of 1. Type 1 diabetesIV. PREVENTION/DELAY OF TYPE 2 long-term complications. Diabetes care is Glycemic control DIABETES, p. S16 complex and requires that many issues, a. Screening and management ofV. DIABETES CARE, p. S16 beyond glycemic control, be addressed. A chronic complications in chil- A. Initial evaluation large body of evidence exists that sup- dren and adolescents with B. Management ports a range of interventions to improve type 1 diabetes C. Glycemic control diabetes outcomes. i. Nephropathy These standards of care are intended 1. Assessment of glycemic control ii. Hypertension to provide clinicians, patients, research- a. Glucose monitoring iii. Dyslipidemia ers, payors, and other interested individ- b. A1C iv. Retinopathy uals with the components of diabetes 2. Glycemic goals in adults v. Celiac disease care, general treatment goals, and tools to D. Pharmacologic and overall ap- vi. Hypothyroidism evaluate the quality of care. While indi- proaches to treatment b. Self-management vidual preferences, comorbidities, and 1. Therapy for type 1 diabetes c. School and day care other patient factors may require modifi- 2. Therapy for type 2 diabetes d. Transition from pediatric to cation of goals, targets that are desirable E. Diabetes self-management educa- adult care for most patients with diabetes are pro- tion 2. Type 2 diabetes vided. These standards are not intended F. Medical nutrition therapy 3. Monogenic diabetes syndromes to preclude clinical judgment or more ex- G. Physical activity B. Preconception care tensive evaluation and management of the H. Psychosocial assessment and care C. Older adults patient by other specialists as needed. I. When treatment goals are not met D. Cystic fibrosis–related diabetes For more detailed information about J. Hypoglycemia VIII. DIABETES CARE IN SPECIFIC management of diabetes, refer to refer- K. Intercurrent illness SETTINGS, p. S43 ences 1–3. L. Bariatric surgery A. Diabetes care in the hospital The recommendations included are M. Immunization 1. Glycemic targets in hospitalized screening, diagnostic, and therapeutic ac-VI. PREVENTION AND MANAGEMENT patients tions that are known or believed to favor- OF DIABETES COMPLICATIONS, p. 2. Anti-hyperglycemic agents in ably affect health outcomes of patients S27 hospitalized patients with diabetes. A grading system (Table 1), A. Cardiovascular disease 3. Preventing hypoglycemia developed by the American Diabetes As-● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● sociation (ADA) and modeled after exist-Originally approved 1988. Most recent review/revision October 2010. ing methods, was utilized to clarify andDOI: 10.2337/dc11-S011© 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly codify the evidence that forms the basis cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons. for the recommendations. The level of ev- org/licenses/by-nc-nd/3.0/ for details. idence that supports each recommenda-care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S11
    • Standards of Medical CareTable 1—ADA evidence grading system for clinical practice recommendations 2-h value in the 75-g oral glucose toler- ance test (OGTT) (4).Level of In 2009, an International Expertevidence Description Committee that included representatives of the ADA, the International DiabetesA Clear evidence from well-conducted, generalizable, randomized controlled Federation (IDF), and the European As- trials that are adequately powered, including: sociation for the Study of Diabetes • Evidence from a well-conducted multicenter trial (EASD) recommended the use of the A1C • Evidence from a meta-analysis that incorporated quality ratings in the test to diagnose diabetes, with a threshold analysis of 6.5% (5), and ADA adopted this cri- Compelling nonexperimental evidence, i.e., “all or none” rule developed terion in 2010 (4). The diagnostic test by Center for Evidence Based Medicine at Oxford should be performed using a method that Supportive evidence from well-conducted randomized controlled trials is certified by the National Glycohemo- that are adequately powered, including: globin Standardization Program (NGSP) • Evidence from a well-conducted trial at one or more institutions and standardized or traceable to the Dia- • Evidence from a meta-analysis that incorporated quality ratings in the betes Control and Complications Trial analysis (DCCT) reference assay. Point-of-careB Supportive evidence from well-conducted cohort studies A1C assays are not sufficiently accurate at • Evidence from a well-conducted prospective cohort study or registry this time to use for diagnostic purposes. • Evidence from a well-conducted meta-analysis of cohort studies Epidemiologic datasets show a simi- Supportive evidence from a well-conducted case-control study lar relationship between A1C and risk ofC Supportive evidence from poorly controlled or uncontrolled studies retinopathy as has been shown for the • Evidence from randomized clinical trials with one or more major or corresponding FPG and 2-h plasma glu- three or more minor methodological flaws that could invalidate the cose thresholds. The A1C has several ad- results vantages to the FPG and OGTT, including • Evidence from observational studies with high potential for bias (such greater convenience, since fasting is not as case series with comparison to historical controls) required; evidence to suggest greater pre- • Evidence from case series or case reports analytical stability; and less day-to-day Conflicting evidence with the weight of evidence supporting the perturbations during periods of stress and recommendation illness. These advantages must be bal-E Expert consensus or clinical experience anced by greater cost, the limited avail- ability of A1C testing in certain regions of the developing world, and the incompletetion is listed after each recommendation lin action, diseases of the exocrine pan- correlation between A1C and average glu-using the letters A, B, C, or E. creas (such as cystic fibrosis), and drug- cose in certain individuals. In addition, These standards of care are revised or chemical-induced (such as in the A1C levels can vary with patients’ ethnic-annually by the ADA’s multidisciplinary treatment of HIV/AIDS or after organ ity (6) as well as with certain anemias andProfessional Practice Committee, incor- transplantation) hemoglobinopathies. For patients with anporating new evidence. Members of the ● Gestational diabetes mellitus (GDM) abnormal hemoglobin but normal red cellProfessional Practice Committee and their (diabetes diagnosed during pregnancy turnover, such as sickle cell trait, an A1Cdisclosed conflicts of interest are listed on that is not clearly overt diabetes) assay without interference from abnormalpage S97. Subsequently, as with all Posi- hemoglobins should be used (an updatedtion Statements, the standards of care are Some patients cannot be clearly classified list is available at www.ngsp.org/interf.reviewed and approved by the Executive as having type 1 or type 2 diabetes. Clin- asp). For conditions with abnormal redCommittee of ADA’s Board of Directors. ical presentation and disease progression cell turnover, such as pregnancy, recent vary considerably in both types of diabe- blood loss or transfusion, or some ane-I. CLASSIFICATION AND tes. Occasionally, patients who otherwise mias, the diagnosis of diabetes must em-DIAGNOSIS OF DIABETES have type 2 diabetes may present with ke- ploy glucose criteria exclusively. toacidosis. Similarly, patients with type 1 The established glucose criteria forA. Classification of diabetes diabetes may have a late onset and slow the diagnosis of diabetes (FPG and 2-hThe classification of diabetes includes (but relentless) progression of disease de- PG) remain valid as well (Table 2). Just asfour clinical classes: spite having features of autoimmune dis- there is less than 100% concordance be- ease. Such difficulties in diagnosis may tween the FPG and 2-h PG tests, there is● Type 1 diabetes (results from -cell de- not perfect concordance between A1C occur in children, adolescents, and struction, usually leading to absolute adults. The true diagnosis may become and either glucose-based test. Analyses of insulin deficiency) more obvious over time. National Health and Nutrition Examina-● Type 2 diabetes (results from a progres- tion Survey (NHANES) data indicate that, sive insulin secretory defect on the assuming universal screening of the undi- background of insulin resistance) B. Diagnosis of diabetes agnosed, the A1C cut point of 6.5%● Other specific types of diabetes due to For decades, the diagnosis of diabetes was identifies one-third fewer cases of undiag- other causes, e.g., genetic defects in based on plasma glucose criteria, either nosed diabetes than a fasting glucose cut -cell function, genetic defects in insu- the fasting plasma glucose (FPG) or the point of 126 mg/dl (7.0 mmol/l) (7).S12 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementTable 2—Criteria for the diagnosis of variability of all the tests, it is also possible Table 3—Categories of increased risk for di-diabetes that when a test whose result was above abetes (prediabetes)*A1C 6.5%. The test should be performed the diagnostic threshold is repeated, the FPG 100–125 mg/dl (5.6–6.9 mmol/l): IFG in a laboratory using a method that is second value will be below the diagnostic or NGSP certified and standardized to the cut point. This is least likely for A1C, 2-h plasma glucose in the 75-g OGTT 140– DCCT assay.* somewhat more likely for FPG, and most 199 mg/dl (7.8–11.0 mmol/l): IGT or likely for the 2-h PG. Barring a laboratory orFPG 126 mg/dl (7.0 mmol/l). Fasting is error, such patients are likely to have test A1C 5.7–6.4% defined as no caloric intake for at least results near the margins of the threshold *For all three tests, risk is continuous, extending 8 h.* for a diagnosis. The healthcare profes- below the lower limit of the range and becoming or sional might opt to follow the patient disproportionately greater at higher ends of the2-h plasma glucose 200 mg/dl (11.1 closely and repeat the testing in 3– 6 range. mmol/l) during an OGTT. The test should months. be performed as described by the World The current diagnostic criteria for di- compared with an A1C of 5.0% (10). In a Health Organization, using a glucose load abetes are summarized in Table 2. community-based study of black and containing the equivalent of 75 g white adults without diabetes, baseline anhydrous glucose dissolved in water.* C. Categories of increased risk for A1C was a stronger predictor of subse- or diabetes (prediabetes) quent diabetes and cardiovascular eventsIn a patient with classic symptoms of In 1997 and 2003, The Expert Committee than fasting glucose (11). Other analyses hyperglycemia or hyperglycemic crisis, a on Diagnosis and Classification of Diabe- suggest that an A1C of 5.7% is associated random plasma glucose 200 mg/dl (11.1 tes Mellitus (8,9) recognized an interme- with diabetes risk similar to that of the mmol/l) diate group of individuals whose glucose high-risk participants in the Diabetes Pre- levels, although not meeting criteria for vention Program (DPP).*In the absence of unequivocal hyperglycemia, re-sult should be confirmed by repeat testing. diabetes, are nevertheless too high to be Hence, it is reasonable to consider an considered normal. These persons were A1C range of 5.7– 6.4% as identifying in- defined as having impaired fasting glu- dividuals with high risk for future diabe-However, in practice, a large portion of cose (IFG) (FPG levels 100 –125 mg/dl tes, a state that may be referred to asthe diabetic population remains unaware [5.6 – 6.9 mmol/l]) or impaired glucose prediabetes (4). As is the case for individ-of their condition. Thus, the lower sensi- tolerance (IGT) (2-h PG values in the uals found to have IFG and IGT, individ-tivity of A1C at the designated cut point OGTT of 140 –199 mg/dl [7.8 –11.0 uals with an A1C of 5.7– 6.4% should bemay well be offset by the test’s greater mmol/l]). It should be noted that the informed of their increased risk for diabe-practicality, and wider application of a World Health Organization (WHO) and a tes as well as CVD and counseled aboutmore convenient test (A1C) may actually number of other diabetes organizations effective strategies to lower their risks (seeincrease the number of diagnoses made. define the cutoff for IFG at 110 mg/dl (6.1 IV. PREVENTION/DELAY OF TYPE 2 DIABETES). As As with most diagnostic tests, a test mmol/l). with glucose measurements, the contin-result diagnostic of diabetes should be re- Individuals with IFG and/or IGT have uum of risk is curvilinear—as A1C rises,peated to rule out laboratory error, unless been referred to as having prediabetes, in- the risk of diabetes rises disproportion-the diagnosis is clear on clinical grounds, dicating the relatively high risk for the fu- ately (10). Accordingly, interventionssuch as a patient with a hyperglycemic ture development of diabetes. IFG and should be most intensive and follow-upcrisis or classic symptoms of hyperglyce- IGT should not be viewed as clinical en- particularly vigilant for those with A1Csmia and a random plasma glucose 200 tities in their own right but rather risk above 6.0%, who should be considered tomg/dl. It is preferable that the same test be factors for diabetes as well as cardiovas- be at very high risk.repeated for confirmation, since there will cular disease (CVD). IFG and IGT are as- Table 3 summarizes the categories ofbe a greater likelihood of concurrence in sociated with obesity (especially increased risk for diabetes.this case. For example, if the A1C is 7.0% abdominal or visceral obesity), dyslipide-and a repeat result is 6.8%, the diagnosis mia with high triglycerides and/or low II. TESTING FOR DIABETESof diabetes is confirmed. However, if two HDL cholesterol, and hypertension. IN ASYMPTOMATICdifferent tests (such as A1C and FPG) are As is the case with the glucose mea- PATIENTSboth above the diagnostic thresholds, the sures, several prospective studies thatdiagnosis of diabetes is also confirmed. used A1C to predict the progression to Recommendations On the other hand, if two different diabetes demonstrated a strong, continu- ● Testing to detect type 2 diabetes andtests are available in an individual and the ous association between A1C and subse- assess risk for future diabetes in asymp-results are discordant, the test whose re- quent diabetes. In a systematic review of tomatic people should be considered insult is above the diagnostic cut point 44,203 individuals from 16 cohort stud- adults of any age who are overweight orshould be repeated, and the diagnosis is ies with a follow-up interval averaging 5.6 obese (BMI 25 kg/m2) and who havemade on the basis of the confirmed test. years (range 2.8 –12 years), those with an one or more additional risk factors forThat is, if a patient meets the diabetes cri- A1C between 5.5 and 6.0% had a sub- diabetes (Table 4). In those withoutterion of the A1C (two results 6.5%) but stantially increased risk of diabetes with these risk factors, testing should beginnot the FPG ( 126 mg/dl or 7.0 mmol/l), 5-year incidences ranging from 9 –25%. at age 45 years. (B)or vice versa, that person should be con- An A1C range of 6.0 – 6.5% had a 5-year ● If tests are normal, repeat testing car-sidered to have diabetes. risk of developing diabetes between 25– ried out at least at 3-year intervals is Since there is preanalytic and analytic 50% and relative risk 20 times higher reasonable. (E)care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S13
    • Standards of Medical CareTable 4—Criteria for testing for diabetes in A. Testing for type 2 diabetes and complications of diabetes within 3 yearsasymptomatic adult individuals risk of future diabetes in adults of a negative test result. In the modeling1. Testing should be considered in all adults Type 2 diabetes is frequently not diag- study, repeat screening every 3 or 5 years who are overweight (BMI 25 kg/m2*) nosed until complications appear, and was cost-effective (12). and have additional risk factors: approximately one-fourth of all people Because of the need for follow-up and • physical inactivity with diabetes in the U.S. may be undiag- discussion of abnormal results, testing • first-degree relative with diabetes nosed. The effectiveness of early identifi- should be carried out within the health • high-risk race/ethnicity (e.g., African cation of prediabetes and diabetes care setting. Community screening out- American, Latino, Native American, through mass testing of asymptomatic in- side a health care setting is not recom- Asian American, Pacific Islander) dividuals has not been proven defini- mended because people with positive • women who delivered a baby weighing tively, and rigorous trials to provide such tests may not seek, or have access to, ap- 9 lb or were diagnosed with GDM proof are unlikely to occur. However, propriate follow-up testing and care. • hypertension ( 140/90 mmHg or on mathematical modeling studies suggest Conversely, there may be failure to ensure therapy for hypertension) that screening independent of risk factors appropriate repeat testing for individuals • HDL cholesterol level 35 mg/dl (0.90 beginning at age 30 or 45 years is highly who test negative. Community screening mmol/l) and/or a triglyceride level 250 cost-effective ( $11,000 per quality- may also be poorly targeted, i.e., it may mg/dl (2.82 mmol/l) adjusted life-year gained) (12). Prediabe- fail to reach the groups most at risk and • women with polycystic ovarian tes and diabetes meet established criteria inappropriately test those at low risk (the syndrome (PCOS) for conditions in which early detection is worried well) or even those already diag- • A1C 5.7%, IGT, or IFG on previous appropriate. Both conditions are com- nosed. testing mon and increasing in prevalence and im- • other clinical conditions associated with pose significant public health burdens. B. Testing for type 2 diabetes in insulin resistance (e.g., severe obesity, There is a long presymptomatic phase be- children acanthosis nigricans) fore the diagnosis of type 2 diabetes is The incidence of type 2 diabetes in ado- • history of CVD usually made. Relatively simple tests are lescents has increased dramatically in the2. In the absence of the above criteria, testing available to detect preclinical disease. Ad- last decade, especially in minority popu- for diabetes should begin at age 45 ditionally, the duration of glycemic bur- lations (21), although the disease remains years. den is a strong predictor of adverse rare in the general pediatric population3. If results are normal, testing should be outcomes, and effective interventions ex- (22). Consistent with recommendations repeated at least at 3-year intervals, with ist to prevent progression of prediabetes for adults, children and youth at in- consideration of more frequent testing to diabetes (see IV. PREVENTION/DELAY OF TYPE creased risk for the presence or the devel- depending on initial results and risk 2 DIABETES) and to reduce risk of compli- opment of type 2 diabetes should be status. cations of diabetes (see VI. PREVENTION AND tested within the health care setting. The MANAGEMENT OF DIABETES COMPLICATIONS). recommendations of the ADA Consensus*At-risk BMI may be lower in some ethnic groups. Recommendations for testing for dia- Statement on Type 2 Diabetes in Children betes in asymptomatic, undiagnosed and Youth (23), with some modifications, adults are listed in Table 4. Testing should are summarized in Table 5.● To test for diabetes or to assess risk of be considered in adults of any age with future diabetes, A1C, FPG, or 2-h 75-g BMI 25 kg/m2 and one or more of the C. Screening for type 1 diabetes OGTT is appropriate. (B) known risk factors for diabetes. Because Generally, people with type 1 diabetes● In those identified with increased risk age is a major risk factor for diabetes, test- present with acute symptoms of diabetes for future diabetes, identify and, if ap- ing of those without other risk factors and markedly elevated blood glucose lev- propriate, treat other CVD risk factors. should begin no later than age 45 years. els, and most cases are diagnosed soon (B) Either A1C, FPG, or the 2-h OGTT is after the onset of hyperglycemia. How- appropriate for testing. The 2-h OGTT ever, evidence from type 1 prevention stud-For many illnesses, there is a major dis- identifies people with either IFG or IGT ies suggests that measurement of islettinction between screening and diagnos- and thus more people at increased risk for autoantibodies identifies individuals whotic testing. However, for diabetes, the the development of diabetes and CVD. It are at risk for developing type 1 diabetes.same tests would be used for “screening” should be noted that the two tests do not Such testing may be appropriate in high-as for diagnosis. Diabetes may be identi- necessarily detect the same individuals. risk individuals, such as those with priorfied anywhere along a spectrum of clinical The efficacy of interventions for primary transient hyperglycemia or those who havescenarios ranging from a seemingly low- prevention of type 2 diabetes (13–19) relatives with type 1 diabetes, in the contextrisk individual who happens to have glu- have primarily been demonstrated among of clinical research studies (see, for ex-cose testing, to a higher-risk individual individuals with IGT, not for individuals ample, http://www2.diabetestrialnet.org).whom the provider tests because of high with IFG (who do not also have IGT) or Widespread clinical testing of asymptom-suspicion of diabetes, to the symptomatic for individuals with specific A1C levels. atic low-risk individuals cannot currentlypatient. The discussion herein is primar- The appropriate interval between be recommended, as it would identifyily framed as testing for diabetes in those tests is not known (20). The rationale for very few individuals in the general popu-without symptoms. Testing for diabetes the 3-year interval is that false negatives lation who are at risk. Individuals whowill also detect individuals at increased will be repeated before substantial time screen positive should be counseledfuture risk for diabetes, herein referred to elapses, and there is little likelihood that about their risk of developing diabetes.as having prediabetes. an individual will develop significant Clinical studies are being conducted toS14 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementTable 5—Testing for type 2 diabetes in for detection and classification of GDM, Table 6—Screening for and diagnosis ofasymptomatic children but its limitations were recognized for GDMCriteria many years. As the ongoing epidemic of Perform a 75-g OGTT, with plasma glucose • Overweight (BMI 85th percentile for obesity and diabetes has led to more type measurement fasting and at 1 and 2 h, age and sex, weight for height 85th 2 diabetes in women of childbearing age, at 24–28 weeks of gestation in women percentile, or weight 120% of ideal for the number of pregnant women with un- not previously diagnosed with overt height) diagnosed type 2 diabetes has increased diabetes.Plus any two of the following risk factors: (24). Because of this, it is reasonable to The OGTT should be performed in the • Family history of type 2 diabetes in first- screen women with risk factors for type 2 morning after an overnight fast of at or second-degree relative diabetes (Table 4) for diabetes at their ini- least 8 h. • Race/ethnicity (Native American, African tial prenatal visit, using standard diagnos- The diagnosis of GDM is made when any of American, Latino, Asian American, tic criteria (Table 2). Women with the following plasma glucose values are Pacific Islander) diabetes found at this visit should receive exceeded: • Signs of insulin resistance or conditions a diagnosis of overt, not gestational, dia- • Fasting 92 mg/dl (5.1 mmol/l) associated with insulin resistance betes. • 1 h 180 mg/dl (10.0 mmol/l) (acanthosis nigricans, hypertension, GDM carries risks for the mother and • 2 h 153 mg/dl (8.5 mmol/l) dyslipidemia, PCOS, or small-for- neonate. The Hyperglycemia and Adverse gestational-age birth weight) Pregnancy Outcomes (HAPO) study (25), • Maternal history of diabetes or GDM a large-scale ( 25,000 pregnant women) during the child’s gestation multinational epidemiologic study, dem- optimizing gestational outcomes forAge of initiation: age 10 years or at onset of onstrated that risk of adverse maternal, women and their babies. puberty, if puberty occurs at a younger fetal, and neonatal outcomes continu- Admittedly, there are few data from age ously increased as a function of maternal randomized clinical trials regarding ther-Frequency: every 3 years glycemia at 24 –28 weeks, even within apeutic interventions in women who will ranges previously considered normal for now be diagnosed with GDM based on pregnancy. For most complications, there only one blood glucose value above thetest various methods of preventing type 1 was no threshold for risk. These results specified cut points (in contrast to thediabetes, or reversing early type 1 diabe- older criteria that stipulated at least two have led to careful reconsideration of thetes, in those with evidence of autoimmu- abnormal values.) Expected benefits to diagnostic criteria for GDM. After delib-nity. their pregnancies and offspring is inferred erations in 2008 –2009, the International Association of Diabetes and Pregnancy from intervention trials that focused onIII. DETECTION AND women with more mild hyperglycemia Study Groups (IADPSG), an internationalDIAGNOSIS OF than identified using older GDM diagnos- consensus group with representativesGESTATIONAL DIABETES tic criteria and that found modest benefitsMELLITUS from multiple obstetrical and diabetes or- ganizations, including ADA, developed (27,28). The frequency of their follow-up revised recommendations for diagnosing and blood glucose monitoring is not yetRecommendations clear, but likely to be less intensive than● Screen for undiagnosed type 2 diabetes GDM. The group recommended that all women not known to have diabetes un- women diagnosed by the older criteria. at the first prenatal visit in those with dergo a 75-g OGTT at 24 –28 weeks of Additional well-designed clinical studies risk factors, using standard diagnostic gestation. Additionally, the group devel- are needed to determine the optimal in- criteria. (B)● In pregnant women not known to have oped diagnostic cut points for the fasting, tensity of monitoring and treatment of diabetes, screen for GDM at 24 –28 1-h, and 2-h plasma glucose measure- women with GDM diagnosed by the new weeks of gestation, using a 75-g 2-h ments that conveyed an odds ratio for ad- criteria (that would not have met the prior OGTT and the diagnostic cut points in verse outcomes of at least 1.75 compared definition of GDM). It is important to note Table 6. (B) with the mean glucose levels in the HAPO that 80 –90% of women in both of the● Screen women with GDM for persistent study. Current screening and diagnostic mild GDM studies (whose glucose values diabetes 6 –12 weeks postpartum. (E) strategies, based on the IADPSG state- overlapped with the thresholds recom-● Women with a history of GDM should ment (26), are outlined in Table 6. mended herein) could be managed with have lifelong screening for the develop- These new criteria will significantly lifestyle therapy alone. ment of diabetes or prediabetes at least increase the prevalence of GDM, primar- Because some cases of GDM may rep- every 3 years. (E) ily because only one abnormal value, not resent preexisting undiagnosed type 2 di- two, is sufficient to make the diagnosis. abetes, women with a history of GDMFor many years, GDM was defined as any The ADA recognizes the anticipated sig- should be screened for diabetes 6 –12degree of glucose intolerance with onset nificant increase in the incidence of GDM weeks postpartum, using nonpregnantor first recognition during pregnancy (8), to be diagnosed by these criteria and is OGTT criteria. Women with a history ofwhether or not the condition persisted af- sensitive to concerns about the “medical- GDM have a greatly increased subsequentter pregnancy, and not excluding the pos- ization” of pregnancies previously catego- risk for diabetes (29) and should be fol-sibility that unrecognized glucose rized as normal. These diagnostic criteria lowed up with subsequent screening forintolerance may have antedated or begun changes are being made in the context of the development of diabetes or prediabe-concomitantly with the pregnancy. This worrisome worldwide increases in obe- tes, as outlined in II. TESTING FOR DIABETES INdefinition facilitated a uniform strategy sity and diabetes rates, with the intent of ASYMPTOMATIC PATIENTS.care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S15
    • Standards of Medical CareTable 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) treatLifestyle Finnish DPS (14) 522 IGT, BMI 25 kg/m2 55 3.2 I-D&E 6 58 (30–70) 8.5 DPP (13) 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 (15) 259* IGT (randomized groups) 45 6 G-D&E 14.5 38 (14–56) 7.9 Toranomon Study 458 IGT (men), BMI 24 55 4 I-D&E 2.4 67 (P 0.043)† 20.6 (35) kg/m2 Indian DPP (19) 269* IGT 46 2.5 I-D&E 23 29 (21–37) 6.4Medications DPP (13) 2,155* IGT, BMI 24 kg/m2, 51 2.8 Metformin (1,700 10.4 31 (17–43) 13.9 FPG 5.3 mmol/l mg) Indian DPP (19) 269* IGT 46 2.5 Metformin (500 mg) 23 26 (19–35) 6.9 STOP-NIDDM (17) 1,419 IGT, FPG 5.6 mmol/l 54 3.2 Acarbose (300 mg) 12.4 25 (10–37) 9.6 XENDOS (36) 3,277 BMI 30 kg/m2 43 4 Orlistat (360 mg) 2.4 37 (14–54) 45.5 DREAM (18) 5,269 IGT or IFG 55 3.0 Rosiglitazone (8 mg) 9.1 60 (54–65) 6.9 Voglibose Ph-3 1,780 IGT 56 3.0 (1-year Vogliobose (0.2 mg) 12.0 40 (18–57) 21 (1-year (37) Rx) Rx)Modified and reprinted with permission (38). 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. DPP, DiabetesPrevention Program; DPS, Diabetes Prevention Study; DREAM, Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication; STOP-NIDDM, Study toPrevent Non-Insulin Dependent Diabetes; XENDOS, Xenical in the prevention of Diabetes in Obese Subjects. I, individual; G, group; D&E, diet and exercise.IV. PREVENTION/DELAY abetes (13–19). These interventions loss and moderate physical activity of atOF TYPE 2 DIABETES include intensive lifestyle modification least 150 min/week). Regarding the more programs that have been shown to be very difficult issue of drug therapy for diabetesRecommendations effective (58% reduction after 3 years) prevention, a consensus panel felt that● Patients with IGT (A), IFG (E), or an and use of the pharmacologic agents met- metformin should be the only drug con- A1C of 5.7– 6.4% (E) should be re- formin, -glucosidase inhibitors, orlistat, sidered (39). For other drugs, the issues of ferred to an effective ongoing support and thiazolidinediones (TZDs), each of cost, side effects, and lack of persistence program targeting weight loss of 7% of which has been shown to decrease inci- of effect in some studies led the panel to body weight and increasing physical dent diabetes to various degrees. A sum- not recommend their use for diabetes pre- activity to at least 150 min/week of mary of major diabetes prevention trials is vention. Metformin, which was signifi- moderate activity such as walking. shown in Table 7. cantly less effective than lifestyle in the● Follow-up counseling appears to be im- Follow-up of all three large studies of DPP and DPPOS, reasonably may be rec- portant for success. (B) lifestyle intervention has shown sustained ommended for very-high-risk individuals● Based on potential cost savings of diabe- reduction in the rate of conversion to type (those with risk factors for diabetes and/or tes prevention, such programs should be 2 diabetes, with 43% reduction at 20 those with more severe or progressive hy- covered by third-party payors. (E) years in the Da Qing study (30), 43% re- perglycemia). Of note, in the DPP met-● Metformin therapy for prevention of duction at 7 years in the Finnish Diabetes formin was most effective compared to type 2 diabetes may be considered in Prevention Study (DPS) (31) and 34% re- lifestyle in those with BMI of at least 35 those at the highest risk for developing duction at 10 years in the U.S. Diabetes kg/m2 and was not significantly better diabetes, such as those with multiple Prevention Program Outcomes Study than placebo in those over age 60 years. risk factors, especially if they demon- (DPPOS) (32). A cost-effectiveness analy- strate progression of hyperglycemia sis suggested that lifestyle interventions as V. DIABETES CARE (e.g., A1C 6%) despite lifestyle inter- delivered in the DPP are cost-effective ventions. (B) (33). Group delivery of the DPP interven- A. Initial evaluation● Monitoring for the development of di- tion in community settings has the poten- A complete medical evaluation should be abetes in those with prediabetes should tial to be significantly less expensive while performed to classify the diabetes, detect be performed every year. (E) still achieving similar weight loss (34). the presence of diabetes complications, Based on the results of clinical trials review previous treatment and glycemicRandomized controlled trials have shown and the known risks of progression of control in patients with established diabe-that individuals at high risk for develop- prediabetes to diabetes, persons with an tes, assist in formulating a managementing diabetes (those with IFG, IGT, or A1C of 5.7– 6.4%, IGT, or IFG should be plan, and provide a basis for continuingboth) can be given interventions that sig- counseled on lifestyle changes with goals care. Laboratory tests appropriate to thenificantly decrease the rate of onset of di- similar to those of the DPP (7% weight evaluation of each patient’s medical con-S16 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementdition should be performed. A focus on Table 8—Components of the comprehensive diabetes evaluationthe components of comprehensive care Medical history(Table 8) will assist the health care team to • Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding)ensure optimal management of the pa- • Eating patterns, physical activity habits, nutritional status, and weight history; growthtient with diabetes. and development in children and adolescents • Diabetes education historyB. Management • Review of previous treatment regimens and response to therapy (A1C records)People with diabetes should receive med- • Current treatment of diabetes, including medications, meal plan, physical activityical care from a physician-coordinated patterns, and results of glucose monitoring and patient’s use of datateam. Such teams may include, but are • DKA frequency, severity, and causenot limited to, physicians, nurse practitio- • Hypoglycemic episodesners, physician’s assistants, nurses, dieti- • Hypoglycemia awarenesstians, pharmacists, and mental health • Any severe hypoglycemia: frequency and causeprofessionals with expertise and a special • History of diabetes-related complicationsinterest in diabetes. It is essential in this • Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history ofcollaborative and integrated team ap- foot lesions; autonomic, including sexual dysfunction and gastroparesis)proach that individuals with diabetes as- • Macrovascular: CHD, cerebrovascular disease, PADsume an active role in their care. • Other: psychosocial problems*, dental disease* The management plan should be Physical examinationformulated as a collaborative therapeu- • Height, weight, BMItic alliance among the patient and fam- • Blood pressure determination, including orthostatic measurements when indicatedily, the physician, and other members of • Fundoscopic examination*the health care team. A variety of strat- • Thyroid palpationegies and techniques should be used to • Skin examination (for acanthosis nigricans and insulin injection sites)provide adequate education and devel- • Comprehensive foot examination:opment of problem-solving skills in the • Inspectionvarious aspects of diabetes manage- • Palpation of dorsalis pedis and posterior tibial pulsesment. Implementation of the manage- • Presence/absence of patellar and Achilles reflexesment plan requires that each aspect is • Determination of proprioception, vibration, and monofilament sensationunderstood and agreed to by the patient Laboratory evaluationand the care providers and that the goals • A1C, if results not available within past 2–3 monthsand treatment plan are reasonable. Any • If not performed/available within past year:plan should recognize diabetes self- • Fasting lipid profile, including total, LDL and HDL cholesterol and triglyceridesmanagement education (DSME) and • Liver function testsongoing diabetes support as an integral • Test for urine albumin excretion with spot urine albumin-to-creatinine ratiocomponent of care. In developing the • Serum creatinine and calculated GFRplan, consideration should be given to • Thyroid-stimulating hormone in type 1 diabetes, dyslipidemia, or women over age 50the patient’s age, school or work sched- yearsule and conditions, physical activity, Referralseating patterns, social situation and • Annual dilated eye examcultural factors, and presence of com- • Family planning for women of reproductive ageplications of diabetes or other medical • Registered dietitian for MNTconditions. • DSME • Dental examination • Mental health professional, if neededC. Glycemic control *See appropriate referrals for these categories.1. Assessment of glycemic controlTwo primary techniques are available for ● For patients using less-frequent insulin in conjunction with intensive insulinhealth providers and patients to assess the injections, noninsulin therapies, or regimens can be a useful tool to lowereffectiveness of the management plan on medical nutrition therapy (MNT) A1C in selected adults (age 25 years)glycemic control: patient self-monitoring alone, SMBG may be useful as a guide to with type 1 diabetes. (A)of blood glucose (SMBG) or interstitial the success of therapy. (E) ● Although the evidence for A1C-glucose, and A1C. ● To achieve postprandial glucose tar- lowering is less strong in children, gets, postprandial SMBG may be appro- teens, and younger adults, CGM maya. Glucose monitoring priate. (E) be helpful in these groups. Success cor- ● When prescribing SMBG, ensure that relates with adherence to ongoing useRecommendations patients receive initial instruction in, of the device. (C)● SMBG should be carried out three or and routine follow-up evaluation of, ● CGM may be a supplemental tool to more times daily for patients using mul- SMBG technique and their ability to use SMBG in those with hypoglycemia un- tiple insulin injections or insulin pump data to adjust therapy. (E) awareness and/or frequent hypoglyce- therapy. (A) ● Continuous glucose monitoring (CGM) mic episodes. (E)care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S17
    • Standards of Medical CareMajor clinical trials of insulin-treated pa- hyperglycemic excursions. Small studies Table 9—Correlation of A1C with averagetients that demonstrated the benefits of in selected patients with type 1 diabetes glucoseintensive glycemic control on diabetes have suggested that CGM use reduces thecomplications have included SMBG as time spent in hypo- and hyperglycemic Mean plasma glucosepart of multifactorial interventions, sug- ranges and may modestly improve glyce-gesting that SMBG is a component of ef- mic control. A larger 26-week random- A1C (%) mg/dl mmol/lfective therapy. SMBG allows patients to ized trial of 322 type 1 patients showed 6 126 7.0evaluate their individual response to ther- that adults age 25 years and older using 7 154 8.6apy and assess whether glycemic targets intensive insulin therapy and CGM expe- 8 183 10.2are being achieved. Results of SMBG can rienced a 0.5% reduction in A1C (from 9 212 11.8be useful in preventing hypoglycemia and 7.6% to 7.1%) compared to usual in- 10 240 13.4adjusting medications (particularly pran- tensive insulin therapy with SMBG (45). 11 269 14.9dial insulin doses), MNT, and physical ac- Sensor use in children, teens, and adults 12 298 16.5tivity. up to age 24 years did not result in signif- These estimates are based on ADAG data of 2,700 The frequency and timing of SMBG icant A1C lowering, and there was no sig- glucose measurements over 3 months per A1C mea-should be dictated by the particular needs nificant difference in hypoglycemia in any surement in 507 adults with type 1, type 2, and noand goals of the patient. SMBG is espe- group. Importantly, the greatest predictor diabetes. The correlation between A1C and averagecially important for patients treated with of A1C-lowering in this study for all age- glucose was 0.92 (51). A calculator for converting A1C results into estimated average glucose (eAG), ininsulin to monitor for and prevent asymp- groups was frequency of sensor use, either mg/dl or mmol/l, is available at http://tomatic hypoglycemia and hyperglyce- which was lower in younger age-groups. professional.diabetes.org/eAG.mia. For most patients with type 1 In a smaller randomized controlled trial ofdiabetes and pregnant women taking in- 129 adults and children with baselinesulin, SMBG is recommended three or A1C 7.0%, outcomes combining A1C quency of A1C testing should bemore times daily. For these populations, and hypoglycemia favored the group uti- dependent on the clinical situation, thesignificantly more frequent testing may be lizing CGM, suggesting that CGM is also treatment regimen used, and the judg-required to reach A1C targets safely with- beneficial for individuals with type 1 dia- ment of the clinician. Some patients without hypoglycemia. The optimal frequency betes who have already achieved excellent stable glycemia well within target may doand timing of SMBG for patients with type control with A1C 7.0 (46). Although well with testing only twice per year,2 diabetes on noninsulin therapy is un- CGM is an evolving technology, emerging while unstable or highly intensively man-clear. A meta-analysis of SMBG in non– data suggest that, in appropriately se- aged patients (e.g., pregnant type 1insulin-treated patients with type 2 lected patients who are motivated to wear women) may be tested more frequentlydiabetes concluded that some regimen of it most of the time, it may offer benefit. than every 3 months. The availability ofSMBG was associated with a reduction in CGM may be particularly useful in those the A1C result at the time that the patientA1C of 0.4%. However, many of the stud- with hypoglycemia unawareness and/or is seen (point-of-care testing) has been re-ies in this analysis also included patient frequent episodes of hypoglycemia, and ported to result in increased intensifica-education with diet and exercise counsel- studies in this area are ongoing. tion of therapy and improvement ining and, in some cases, pharmacologic in- glycemic control (49,50).tervention, making it difficult to assess the b. A1C The A1C test is subject to certain lim-contribution of SMBG alone to improved itations. Conditions that affect erythro-control (40). Several recent trials have Recommendations cyte turnover (hemolysis, blood loss) andcalled into question the clinical utility and ● Perform the A1C test at least two times hemoglobin variants must be considered,cost-effectiveness of routine SMBG in a year in patients who are meeting treat- particularly when the A1C result does notnon–insulin-treated patients (41– 43). ment goals (and who have stable glyce- correlate with the patient’s clinical situa- Because the accuracy of SMBG is in- mic control). (E) tion (44). In addition, A1C does not pro-strument and user dependent (44), it is ● Perform the A1C test quarterly in pa- vide a measure of glycemic variability orimportant to evaluate each patient’s mon- tients whose therapy has changed or hypoglycemia. For patients prone to gly-itoring technique, both initially and at who are not meeting glycemic goals. (E) cemic variability (especially type 1 pa-regular intervals thereafter. In addition, ● Use of point-of-care testing for A1C al- tients, or type 2 patients with severeoptimal use of SMBG requires proper in- lows for timely decisions on therapy insulin deficiency), glycemic control isterpretation of the data. Patients should changes, when needed. (E) best judged by the combination of resultsbe taught how to use the data to adjust of SMBG testing and the A1C. The A1Cfood intake, exercise, or pharmacological Because A1C is thought to reflect average may also serve as a check on the accuracytherapy to achieve specific glycemic goals, glycemia over several months (44), and of the patient’s meter (or the patient’s re-and these skills should be reevaluated pe- has strong predictive value for diabetes ported SMBG results) and the adequacy ofriodically. complications (47,48), A1C testing the SMBG testing schedule. CGM through the measurement of in- should be performed routinely in all pa- Table 9 contains the correlation be-terstitial glucose (which correlates well tients with diabetes, at initial assessment tween A1C levels and mean plasma glu-with plasma glucose) is available. These and then as part of continuing care. Mea- cose levels based on data from thesensors require calibration with SMBG, surement approximately every 3 months international A1C-Derived Average Glu-and the latter are still recommended for determines whether a patient’s glycemic cose (ADAG) trial utilizing frequentmaking acute treatment decisions. CGM targets have been reached and main- SMBG and CGM in 507 adults (83% Cau-devices also have alarms for hypo- and tained. For any individual patient, the fre- casian) with type 1, type 2, and no diabe-S18 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementtes (51). The American Diabetes the diagnosis of diabetes, is associated The Veterans Affairs Diabetes TrialAssociation and American Association of with long-term reduction in macrovas- (VADT) showed significant reductions inClinical Chemists have determined that cular disease. Therefore, a reasonable albuminuria with intensive (achieved me-the correlation (r 0.92) is strong A1C goal for many nonpregnant adults dian A1C 6.9%) compared to standardenough to justify reporting both an A1C is 7%. (B) glycemic control, but no difference in ret-result and an estimated average glucose ● Because additional analyses from sev- inopathy and neuropathy (60,61). The(eAG) result when a clinician orders the eral randomized trials suggest a small Action in Diabetes and Vascular Disease:A1C test. The table in previous versions of but incremental benefit in microvascu- Preterax and Diamicron Modified Releasethe Standards of Medical Care in Diabetes lar outcomes with A1C values closer to Controlled Evaluation (ADVANCE) studydescribing the correlation between A1C normal, providers might reasonably of intensive versus standard glycemicand mean glucose was derived from rela- suggest more stringent A1C goals for control in type 2 diabetes found a statis-tively sparse data (one 7-point profile selected individual patients, if this can tically significant reduction in albumin-over 1 day per A1C reading) in the pri- be achieved without significant hypo- uria with an A1C target of 6.5%marily Caucasian type 1 diabetic partici- glycemia or other adverse effects of (achieved median A1C 6.3%) comparedpants in the DCCT (52). Clinicians treatment. Such patients might include to standard therapy achieving a medianshould note that the numbers in the table those with short duration of diabetes, A1C of 7.0% (62). Recent analyses fromare now different, as they are based on long life expectancy, and no significant the Action to Control Cardiovascular Risk 2,800 readings per A1C in the ADAG CVD. (B) in Diabetes (ACCORD) trial have showntrial. ● Conversely, less stringent A1C goals lower rates of measures of microvascular In the ADAG trial, there were no sig- may be appropriate for patients with a complications in the intensive glycemicnificant differences among racial and eth- history of severe hypoglycemia, limited control arm compared with the standardnic groups in the regression lines between life expectancy, advanced microvascu- arm (63,64).A1C and mean glucose, although there lar or macrovascular complications, ex- Epidemiological analyses of thewas a trend toward a difference between tensive comorbid conditions, and those DCCT and UKPDS (47,48) demonstrate aAfrican/African American participants with longstanding diabetes in whom curvilinear relationship between A1C andand Caucasian ones that might have been the general goal is difficult to attain de- microvascular complications. Such anal-significant had more African/African spite DSME, appropriate glucose mon- yses suggest that, on a population level,American participants been studied. A re- itoring, and effective doses of multiple the greatest number of complications willcent study comparing A1C with CGM glucose-lowering agents including in- be averted by taking patients from verydata in 48 type 1 diabetic children found sulin. (C) poor control to fair or good control. Thesea highly statistically significant correla- analyses also suggest that further loweringtion between A1C and mean blood glu- Glycemic control is fundamental to the of A1C from 7 to 6% is associated withcose, although the correlation (r 0.7) management of diabetes. The DCCT (47) further reduction in the risk of microvas-was significantly lower than in the ADAG (in patients with type 1 diabetes), the Ku- cular complications, albeit the absolutetrial (53). Whether there are significant mamoto study (54), and the UK Prospec- risk reductions become much smaller.differences in how A1C relates to average tive Diabetes Study (UKPDS) (55,56) Given the substantially increased risk ofglucose in children or in African Ameri- (both in patients with type 2 diabetes) hypoglycemia (particularly in those withcan patients is an area for further study. were prospective, randomized, controlled type 1 diabetes, but also in the recent typeFor the time being, the question has not trials of intensive versus standard glyce- 2 trials), the concerning mortality find-led to different recommendations about mic control in patients with relatively re- ings in the ACCORD trial (65), and thetesting A1C or to different interpretations cently diagnosed diabetes. These trials relatively much greater effort required toof the clinical meaning of given levels of showed definitively that improved glyce- achieve near-normoglycemia, the risks ofA1C in those populations. mic control is associated with signifi- lower targets may outweigh the potential For patients in whom A1C/eAG and cantly decreased rates of microvascular benefits on microvascular complicationsmeasured blood glucose appear discrep- (retinopathy and nephropathy) and neu- on a population level. However, selectedant, clinicians should consider the possi- ropathic complications. Follow up of the individual patients, especially those withbilities of hemoglobinopathy or altered DCCT cohorts in the Epidemiology of Di- little comorbidity and long life expect-red cell turnover, and the options of more abetes Interventions and Complications ancy (who may reap the benefits of fur-frequent and/or different timing of SMBG (EDIC) study (57,58) and of the UKPDS ther lowering of glycemia below 7%) may,or use of CGM. Other measures of chronic cohort (59) has shown persistence of at patient and provider judgment, adoptglycemia such as fructosamine are avail- these microvascular benefits in previously glycemic targets as close to normal as pos-able, but their linkage to average glucose intensively treated subjects, even though sible as long as significant hypoglycemiaand their prognostic significance are not their glycemic control has been equiva- does not become a barrier.as clear as is the case for A1C. lent to that of previous standard arm sub- Whereas many epidemiologic studies jects during follow-up. and meta-analyses (66,67) have clearly2. Glycemic goals in adults Subsequent trials in patients with shown a direct relationship between A1C more long-standing type 2 diabetes, de- and CVD, the potential of intensive glyce-Recommendations signed primarily to look at the role of mic control to reduce CVD has been less● Lowering A1C to below or around 7% intensive glycemic control on cardiovas- clearly defined. In the DCCT, there was a has been shown to reduce microvascu- cular outcomes also confirmed a benefit, trend toward lower risk of CVD events lar and neuropathic complications of although more modest, on onset or pro- with intensive control. However, 9-year diabetes and, if implemented soon after gression of microvascular complications. post-DCCT follow-up of the cohort hascare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S19
    • Standards of Medical Careshown that participants previously ran- explanation for the excess mortality in the concept, data from an ancillary study ofdomized to the intensive arm had a 42% intensive arm. The ACCORD investiga- the VADT demonstrated that intensivereduction (P 0.02) in CVD outcomes tors subsequently published additional glycemic control was quite effective in re-and a 57% reduction (P 0.02) in the analyses showing no increase in mortality ducing CVD events in individuals withrisk of nonfatal myocardial infarction in the intensive arm participants who less atherosclerosis at baseline (assessed(MI), stroke, or CVD death compared achieved A1C levels 7% or in those who by coronary calcium) but not in personswith those previously in the standard arm lowered their A1C quickly after trial en- with more extensive baseline atheroscle-(68). The benefit of intensive glycemic rollment. In fact, the converse was ob- rosis (72).control in this type 1 cohort has recently served—those at highest risk for mortality The evidence for a cardiovascularbeen shown to persist for several decades were participants in the intensive arm benefit of intensive glycemic control pri-(69). with the highest A1C levels (71). marily rests on long-term follow-up of The UKPDS trial of type 2 diabetes The primary outcome of ADVANCE study cohorts treated early in the courseobserved a 16% reduction in cardiovascu- was a combination of microvascular of type 1 and type 2 diabetes and subsetlar complications (combined fatal or non- events (nephropathy and retinopathy) analyses of ACCORD, ADVANCE, andfatal MI and sudden death) in the and major adverse cardiovascular events VADT. A recent group-level meta-intensive glycemic control arm, although (MI, stroke, and cardiovascular death). analysis of the latter three trials suggeststhis difference was not statistically signif- Intensive glycemic control significantly that glucose lowering has a modest (9%)icant (P 0.052), and there was no sug- reduced the primary end point, although but statistically significant reduction ingestion of benefit on other CVD outcomes this was due to a significant reduction in major CVD outcomes, primarily nonfatalsuch as stroke. However, 10 years of fol- the microvascular outcome, primarily de- MI, with no significant effect on mortality.low-up of the UKPDS cohort demon- velopment of macroalbuminuria, with no A prespecified subgroup analysis sug-strated, for participants originally significant reduction in the macrovascu- gested that major CVD outcome reduc-randomized to intensive glycemic control lar outcome. There was no difference in tion occurred in patients without knowncompared with those randomized to con- overall or cardiovascular mortality be- CVD at baseline (HR 0.84 [95% CI 0.74 –ventional glycemic control, long-term re- tween the intensive compared with the 0.94]) (73). Conversely, the mortalityductions in MI (15% with sulfonylurea or standard glycemic control arms (62). findings in ACCORD and subgroup anal-insulin as initial pharmacotherapy, 33% The VADT randomized participants yses of VADT suggest that the potentialwith metformin as initial pharmacother- with type 2 diabetes uncontrolled on in- risks of very intensive glycemic controlapy, both statistically significant) and in sulin or maximal dose oral agents (me- may outweigh its benefits in some pa-all-cause mortality (13 and 27%, respec- dian entry A1C 9.4%) to a strategy of tients, such as those with very long dura-tively, both statistically significant) (59). intensive glycemic control (goal A1C tion of diabetes, known history of severe Results of three large trials 6.0%) or standard glycemic control, hypoglycemia, advanced atherosclerosis,(ACCORD, ADVANCE, and VADT) sug- with a planned A1C separation of at least and advanced age/frailty. Certainly, pro-gested no significant reduction in CVD 1.5%. The primary outcome of the VADT viders should be vigilant in preventing se-outcomes with intensive glycemic control was a composite of CVD events. The cu- vere hypoglycemia in patients within these populations, who had more ad- mulative primary outcome was nonsig- advanced disease and should not aggres-vanced diabetes than UKPDS partici- nificantly lower in the intensive arm (60). sively attempt to achieve near-normalpants. Details of these three studies are Unlike the UKPDS, which was carried A1C levels in patients in whom such areviewed extensively in a recent ADA po- out in patients with newly diagnosed di- target cannot be reasonably easily andsition statement (70). abetes, all three of the recent type 2 car- safely achieved. The glycemic control arm of diovascular trials were conducted in Recommended glycemic goals forACCORD was halted early due to the participants with established diabetes many nonpregnant adults are shown infinding of an increased rate of mortality in (mean duration 8 –11 years) and either Table 10. The recommendations arethe intensive arm compared with the stan- known CVD or multiple risk factors, sug- based on those for A1C values, with listeddard arm (1.41% vs. 1.14% per year; HR gesting the presence of established ath- blood glucose levels that appear to corre-1.22 [95% CI 1.01 to 1.46]); with a sim- erosclerosis. Subset analyses of the three late with achievement of an A1C of 7%.ilar increase in cardiovascular deaths. The trials suggested a significant benefit of in- Less-stringent treatment goals may be ap-primary outcome of ACCORD (MI, tensive glycemic control on CVD in par- propriate for adults with limited life ex-stroke, or cardiovascular death) was ticipants with shorter duration of pectancies or advanced vascular disease.lower in the intensive glycemic control diabetes, lower A1C at entry, and/or or Glycemic goals for children are providedgroup, due to a reduction in nonfatal MI, absence of known CVD. The DCCT-EDIC in VII.A.1.a. Glycemic control. Severe orbut this reduction was not statistically sig- study and the long-term follow-up of the frequent hypoglycemia is an absolute in-nificant when the study was terminated UKPDS cohort both suggest that intensive dication for the modification of treatment(65). glycemic control initiated soon after diag- regimens, including setting higher glyce- The potential cause of excess deaths nosis of diabetes in patients with a lower mic goals.in the intensive group of the ACCORD level of CVD risk may impart long-term The issue of pre- versus postprandialhas been difficult to pinpoint. Explor- protection from CVD events. As is the SMBG targets is complex (74). Elevatedatory analyses of the mortality findings of case with microvascular complications, it postchallenge (2-h OGTT) glucose valuesACCORD (evaluating variables including may be that glycemic control plays a have been associated with increased car-weight gain, use of any specific drug or greater role before macrovascular disease diovascular risk independent of FPG indrug combination, and hypoglycemia) is well developed and minimal or no role some epidemiological studies. In diabeticwere reportedly unable to identify a clear when it is advanced. Consistent with this subjects, some surrogate measures of vas-S20 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementTable 10—Summary of glycemic recommendations for many nonpregnant adults with type 1 diabetes consists of the followingdiabetes components: 1) use of multiple dose in-A1C 7.0%* sulin injections (three to four injectionsPreprandial capillary plasma glucose 70–130 mg/dl* (3.9–7.2 mmol/l) per day of basal and prandial insulin) orPeak postprandial capillary plasma glucose† 180 mg/dl* ( 10.0 mmol/l) CSII therapy; 2) matching of prandial in- • Goals should be individualized based on*: sulin to carbohydrate intake, premeal • duration of diabetes blood glucose, and anticipated activity; • age/life expectancy and 3) for many patients (especially if hy- • comorbid conditions poglycemia is a problem), use of insulin • known CVD or advanced microvascular analogs. There are excellent reviews avail- complications able that guide the initiation and manage- • hypoglycemia unawareness ment of insulin therapy to achieve desired • individual patient considerations glycemic goals (3,79,81). • More or less stringent glycemic goals may Because of the increased frequency of be appropriate for individual patients. other autoimmune diseases in type 1 dia- • Postprandial glucose may be targeted if betes, screening for thyroid dysfunction, A1C goals are not met despite reaching vitamin B12 deficiency, or celiac disease preprandial glucose goals. should be considered based on signs andPostprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peak symptoms. Periodic screening in absencelevels in patients with diabetes. of symptoms has been recommended, but the effectiveness and optimal frequency are unclear.cular pathology, such as endothelial dys- • 2-h postmeal 120 mg/dl (6.7function, are negatively affected by mmol/l)postprandial hyperglycemia (75). It is For women with preexisting type 1 or 2. Therapy for type 2 diabetesclear that postprandial hyperglycemia, type 2 diabetes who become pregnant, a The ADA and the EASD published an ex-like preprandial hyperglycemia, contrib- recent consensus statement (78) recom- pert consensus statement on the approachutes to elevated A1C levels, with its rela- mended the following as optimal glyce- to management of hyperglycemia in indi-tive contribution being higher at A1C mic goals, if they can be achieved without viduals with type 2 diabetes (82). High-levels that are closer to 7%. However, out- excessive hypoglycemia: lights of this approach are: intervention atcome studies have clearly shown A1C to the time of diagnosis with metformin inbe the primary predictor of complica- ● premeal, bedtime, and overnight glu- combination with lifestyle changes (MNTtions, and landmark glycemic control tri- cose 60 –99 mg/dl (3.3–5.4 mmol/l) and exercise) and continuing timely aug-als such as the DCCT and UKPDS relied ● peak postprandial glucose 100 –129 mentation of therapy with additionaloverwhelmingly on preprandial SMBG. mg/dl (5.4 –7.1mmol/l) agents (including early initiation of insu-Additionally, a randomized controlled ● A1C 6.0% lin therapy) as a means of achieving andtrial in patients with known CVD found maintaining recommended levels of gly-no CVD benefit of insulin regimens tar- D. Pharmacologic and overall cemic control (i.e., A1C 7% for mostgeting postprandial glucose compared approaches to treatment patients). As A1C targets are not achieved,with targeting preprandial glucose (76). A treatment intensification is based on thereasonable recommendation for post- 1. Therapy for type 1 diabetes addition of another agent from a differentprandial testing and targets is that for in- The DCCT clearly showed that intensive class. The overall objective is to achievedividuals who have premeal glucose insulin therapy (three or more injections and maintain glycemic control and tovalues within target but have A1C values per day of insulin, or continuous subcu- change interventions when therapeuticabove target, monitoring postprandial taneous insulin infusion (CSII) (insulin goals are not being met.plasma glucose (PPG) 1–2 h after the start pump therapy) was a key part of im- The algorithm took into account theof the meal and treatment aimed at reduc- proved glycemia and better outcomes evidence for A1C-lowering of the individ-ing PPG values to 180 mg/dl may help (47,68). At the time of the study, therapy ual interventions, their additive effects,lower A1C. was carried out with short- and interme- and their expense. The precise drugs used As regards goals for glycemic control diate-acting human insulins. Despite bet- and their exact sequence may not be asfor women with GDM, recommendations ter microvascular outcomes, intensive important as achieving and maintainingfrom the Fifth International Workshop- insulin therapy was associated with a high glycemic targets safely. Medications notConference on Gestational Diabetes (77) rate in severe hypoglycemia (62 episodes included in the consensus algorithm, ow-were to target maternal capillary glucose per 100 patient-years of therapy). Since ing to less glucose-lowering effectiveness,concentrations of: the time of the DCCT, a number of rapid- limited clinical data, and/or relative ex- acting and long-acting insulin analogs pense, still may be appropriate choices in• Preprandial 95 mg/dl (5.3 mmol/l) have been developed. These analogs are individual patients to achieve glycemic and either associated with less hypoglycemia with goals. Initiation of insulin at time of diagno- • 1-h postmeal 140 mg/dl (7.8 equal A1C-lowering in type 1 diabetes sis is recommended for individuals present- mmol/l) (79,80). ing with weight loss or other severe or Therefore, recommended therapy for hyperglycemic symptoms or signs.care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S21
    • Standards of Medical CareE. Diabetes self-management model working in collaboration with F. Medical nutrition therapyeducation health care professionals. Patient- centered care is respectful of and respon-Recommendations sive to individual patient preferences, General recommendations● People with diabetes should receive di- needs, and values and ensures that patient ● Individuals who have prediabetes or di- abetes self-management education values guide all decision making (91). abetes should receive individualized (DSME) according to national stan- medical nutrition therapy (MNT) as dards when their diabetes is diagnosed Evidence for the benefits of DSME needed to achieve treatment goals, pref- and as needed thereafter. (B) Multiple studies have found that DSME is erably provided by a registered dietitian● Effective self-management and quality associated with improved diabetes familiar with the components of diabe- of life are the key outcomes of DSME knowledge and improved self-care behav- tes MNT. (A) and should be measured and moni- ior (83), improved clinical outcomes such ● Because MNT can result in cost-savings tored as part of care. (C) as lower A1C (84,85,87,88,92), lower and improved outcomes (B), MNT● DSME should address psychosocial is- self-reported weight (83), improved qual- should be adequately covered by insur- sues, since emotional well-being is as- ity of life (86,93), healthy coping (94), ance and other payors. (E) sociated with positive diabetes and lower costs (95). Better outcomes outcomes. (C) were reported for DSME interventions● Because DSME can result in cost- that were longer and included follow-up Energy balance, overweight, and savings and improved outcomes (B), support (83,96 –99), that were culturally obesity ● In overweight and obese insulin- DSME should be adequately reim- (100,101) and age appropriate (102,103) bursed by third-party payors. (E) and tailored to individual needs and pref- resistant individuals, modest weight erences, and that addressed psychosocial loss has been shown to reduce insulinDSME is an essential element of diabetes issues and incorporated behavioral strat- resistance. Thus, weight loss is recom-care (83– 88), and national standards for egies (83,87,104 –106). Both individual mended for all overweight or obese in-DSME (89) are based on evidence for its and group approaches have been found dividuals who have or are at risk forbenefits. Education helps people with di- effective (107–110). There is growing ev- diabetes. (A) ● For weight loss, either low-carbohydrate,abetes initiate effective self-management idence for the role of community healthand cope with diabetes when they are first workers and peer (111,112) and lay lead- low-fat calorie-restricted, or Mediterra-diagnosed. Ongoing DSME and support ers (113) in delivering DSME and support nean diets may be effective in the short-also help people with diabetes maintain in addition to the core team (114). term (up to 2 years). (A) ● For patients on low-carbohydrate diets,effective self-management throughout a Diabetes education is associated withlifetime of diabetes as they face new chal- increased use of primary and preventive monitor lipid profiles, renal function,lenges and treatment advances become services and lower use of acute, inpatient and protein intake (in those with ne-available. DSME helps patients optimize hospital services (95). Patients who par- phropathy), and adjust hypoglycemicmetabolic control, prevent and manage ticipate in diabetes education are more therapy as needed. (E) ● Physical activity and behavior modifi-complications, and maximize quality of likely to follow best practice treatmentlife in a cost-effective manner (90). recommendations, particularly among cation are important components of DSME is the ongoing process of facil- the Medicare population, and have lower weight loss programs and are mostitating the knowledge, skill, and ability Medicare and commercial claim costs helpful in maintenance of weight loss.necessary for diabetes self-care. This pro- (115). (B)cess incorporates the needs, goals, and lifeexperiences of the person with diabetes. National standards for DSMEThe overall objectives of DSME are to sup- National standards for DSME are de- Recommendations for primaryport informed decision-making, self-care signed to define quality DSME and to as- prevention of diabetesbehaviors, problem-solving, and active sist diabetes educators in a variety of ● Among individuals at high risk for de-collaboration with the health care team to settings to provide evidence-based educa- veloping type 2 diabetes, structuredimprove clinical outcomes, health status, tion (89). The standards, most recently programs that emphasize lifestyleand quality of life in a cost-effective man- revised in 2007, are reviewed and up- changes that include moderate weightner (89). dated every 5 years by a task force repre- loss (7% body weight) and regular Current best practice of DSME is a senting key organizations involved in the physical activity (150 min/week),skills-based approach that focuses on field of diabetes education and care. with dietary strategies including re-helping those with diabetes to make in- duced calories and reduced intake offormed self-management choices. DSME Reimbursement for DSME dietary fat, can reduce the risk for de-has changed from a didactic approach fo- DSME, when provided by a program that veloping diabetes and are thereforecusing on providing information to more meets the national standards for DSME and recommended. (A)theoretically based empowerment models is recognized by the ADA or other approval ● Individuals at high risk for type 2 dia-that focus on helping those with diabetes bodies, is reimbursed as partof the Medicare betes should be encouraged to achievemake informed self-management deci- program as overseen by the Centers for Medi- the U.S. Department of Agriculturesions. Care of diabetes has shifted to an care and Medicaid Services (CMS) (www. (USDA) recommendation for dietary fi-approach that is more patient centered cms.hhs.gov/DiabetesSelfManagement). ber (14 g fiber/1,000 kcal) and foodsand places the person with diabetes and DSME is also covered by a growing number containing whole grains (one-half ofhis or her family at the center of the care of other health insurance plans. grain intake). (B)S22 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementRecommendations for management volvement of the person with prediabetes lar events in subjects with type 2 diabetes.of diabetes or diabetes. Because of the complexity of One-year results of the intensive lifestyle nutrition issues, it is recommended that a intervention in this trial show an averageMacronutrients in diabetes registered dietitian who is knowledgeable 8.6% weight loss, significant reduction ofmanagement and skilled in implementing nutrition A1C, and reduction in several CVD risk● The best mix of carbohydrate, protein, therapy into diabetes management and factors (134), with benefits sustained at 4 and fat may be adjusted to meet the education be the team member who pro- years (135). When completed, the Look metabolic goals and individual prefer- vides MNT. AHEAD study should provide insight into ences of the person with diabetes. (E) Clinical trials/outcome studies of the effects of long-term weight loss on im-● Monitoring carbohydrate, whether by MNT have reported decreases in A1C at portant clinical outcomes. carbohydrate counting, choices, or ex- 3– 6 months ranging from 0.25% to 2.9% The optimal macronutrient distribu- perience-based estimation, remains a with higher reductions seen in type 2 di- tion of weight loss diets has not been es- key strategy in achieving glycemic con- abetes of shorter duration. Multiple stud- tablished. Although low-fat diets have trol. (A) ies have demonstrated sustained traditionally been promoted for weight● For individuals with diabetes, the use of improvements in A1C at 12 months and loss, several randomized controlled trials the glycemic index and glycemic load longer when an Registered Dietitian pro- found that subjects on low-carbohydrate may provide a modest additional bene- vided follow-up visits ranging from diets ( 130 g/day of carbohydrate) lost fit for glycemic control over that ob- monthly to three sessions per year (117– more weight at 6 months than subjects on served when total carbohydrate is 124). Studies in nondiabetic people sug- low-fat diets (136,137); however, at 1 considered alone. (B) gest that MNT reduces LDL cholesterol by year, the difference in weight loss be-● Saturated fat intake should be 7% of 15–25 mg/dl up to 16% (125) and sup- tween the low-carbohydrate and low-fat total calories. (A) port a role for lifestyle modification in diets was not significant, and weight loss● Reducing intake of trans fat lowers LDL treating hypertension (125,126). was modest with both diets. A study com- cholesterol and increases HDL choles- Because of the effects of obesity on paring low-fat to low-carbohydrate diets, terol (A), therefore intake of trans fat insulin resistance, weight loss is an im- both combined with a comprehensive should be minimized. (E) portant therapeutic objective for over- lifestyle program, showed the same weight or obese individuals with amount of weight loss (7%) at 2 years inOther nutrition recommendations prediabetes or diabetes (127). Short-term both groups (138). Another study of over-● If adults with diabetes choose to use studies have demonstrated that moderate weight women randomized to one of four alcohol, daily intake should be limited weight loss (5% of body weight) in sub- diets showed significantly more weight to a moderate amount (one drink per jects with type 2 diabetes is associated loss at 12 months with the Atkins low- day or less for adult women and two with decreased insulin resistance, im- carbohydrate diet than with higher- drinks per day or less for adult men). proved measures of glycemia and lipemia, carbohydrate diets (139). Changes in (E) and reduced blood pressure (128); long- serum triglyceride and HDL cholesterol● Routine supplementation with antioxi- er-term studies (52 weeks) showed mixed were more favorable with the low- dants, such as vitamins E and C and effects on A1C in adults with type 2 dia- carbohydrate diets. In one study, those carotene, is not advised because of lack betes (129 –131), and in some studies re- subjects with type 2 diabetes demon- of evidence of efficacy and concern re- sults were confounded by pharmacologic strated a greater decrease in A1C with a lated to long-term safety. (A) weight loss therapy. A systematic review low-carbohydrate diet than with a low-fat● Individualized meal planning should of 80 weight loss studies of 1 year in diet (137). A recent meta-analysis showed include optimization of food choices to duration demonstrated that moderate that at 6 months, low-carbohydrate diets meet recommended dietary allowance weight loss achieved through diet alone, were associated with greater improve- (RDA)/dietary reference intake (DRI) diet and exercise, and meal replacements ments in triglyceride and HDL cholesterol for all micronutrients. (E) can be achieved and maintained (4.8 – 8% concentrations than low-fat diets; how- weight loss at 12 months) (132). The mul- ever, LDL cholesterol was significantlyMNT is an integral component of diabetes tifactorial intensive lifestyle intervention higher on the low-carbohydrate dietsprevention, management, and self- employed in the DPP, which included re- (140). In a 2-year dietary interventionmanagement education. In addition to its duced intake of fat and calories, led to study, Mediterranean and low-carbohy-role in preventing and controlling diabe- weight loss averaging 7% at 6 months and drate diets were found to be effective andtes, ADA recognizes the importance of maintenance of 5% weight loss at 3 years, safe alternatives to a low-fat diet fornutrition as an essential component of an associated with a 58% reduction in inci- weight reduction in moderately obeseoverall healthy lifestyle. A full review of dence of type 2 diabetes (13). A recent participants (141).the evidence regarding nutrition in pre- randomized controlled trial looking at The RDA for digestible carbohydrateventing and controlling diabetes and its high-risk individuals in Spain showed the is 130 g/day and is based on providingcomplications and additional nutrition- Mediterranean dietary pattern reduced adequate glucose as the required fuel forrelated recommendations can be found in the incidence of diabetes in the absence of the central nervous system without reli-the ADA position statement, “Nutrition weight loss by 52% compared to the low- ance on glucose production from ingestedRecommendations and Interventions for fat control group (133). Look AHEAD protein or fat. Although brain fuel needsDiabetes,” published in 2007 and up- (Action for Health in Diabetes) is a large can be met on lower-carbohydrate diets,dated for 2008 (116). Achieving nutri- clinical trial designed to determine long term metabolic effects of very-low-tion-related goals requires a coordinated whether long-term weight loss will im- carbohydrate diets are unclear, and suchteam effort that includes the active in- prove glycemia and prevent cardiovascu- diets eliminate many foods that are im-care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S23
    • Standards of Medical Careportant sources of energy, fiber, vitamins, high-risk individuals (13–15). Structured with multiple cardiovascular risk factorsand minerals and are important in dietary exercise interventions of at least 8 weeks’ for coronary artery disease (CAD). As dis-palatability (142). duration have been shown to lower A1C cussed more fully in VI.A.5. Coronary Although numerous studies have at- by an average of 0.66% in people with heart disease screening and treatment, thetempted to identify the optimal mix of type 2 diabetes, even with no significant area of screening asymptomatic diabeticmacronutrients for meal plans of people change in BMI (146). Higher levels of ex- patients for CAD remains unclear, and awith diabetes, it is unlikely that one such ercise intensity are associated with greater recent ADA consensus statement on thiscombination of macronutrients exists. improvements in A1C and in fitness issue concluded that routine screening isThe best mix of carbohydrate, protein, (147). A new joint position statement of not recommended (154). Providersand fat appears to vary depending on in- the American Diabetes Association and should use clinical judgment in this area.dividual circumstances. It must be clearly the American College of Sports Medicine Certainly, high risk patients should be en-recognized that regardless of the macronu- summarizes the evidence for the benefits couraged to start with short periods oftrient mix, total caloric intake must be ap- of exercise in people with type 2 diabetes low intensity exercise and increase the in-propriate to weight management goal. (148). tensity and duration slowly.Further, individualization of the macronu- Providers should assess patients fortrient composition will depend on the met- Frequency and type of exercise conditions that might contraindicate cer-abolic status of the patient (e.g., lipid The U.S. Department of Health and Hu- tain types of exercise or predispose to in-profile, renal function) and/or food prefer- man Services’ Physical Activity Guide- jury, such as uncontrolled hypertension,ences. Plant-based diets (vegan or vegetar- lines for Americans (149) suggest that severe autonomic neuropathy, severe pe-ian) that are well planned and nutritionally adults over age 18 years do 150 min/week ripheral neuropathy or history of footadequate have also been shown to improve of moderate-intensity, or 75 min/week of lesions, and unstable proliferative reti-metabolic control (143,144). vigorous aerobic physical activity, or an nopathy. The patient’s age and previous The primary goal with respect to di- equivalent combination of the two. In ad- physical activity level should be consid-etary fat in individuals with diabetes is to dition, the guidelines suggest that adults ered.limit saturated fatty acids, trans fatty acids, also do muscle-strengthening activitiesand cholesterol intake so as to reduce risk that involve all major muscle groups two Exercise in the presence offor CVD. Saturated and trans fatty acids are or more days per week. The guidelines nonoptimal glycemic controlthe principal dietary determinants of suggest that adults over age 65 years, or Hyperglycemia. When people with typeplasma LDL cholesterol. There is a lack of those with disabilities, follow the adult 1 diabetes are deprived of insulin forevidence on the effects of specific fatty acids guidelines if possible or (if this is not pos- 12– 48 h and are ketotic, exercise canon people with diabetes, so the recom- sible) be as physically active as they are worsen hyperglycemia and ketosis (155);mended goals are consistent with those for able. Studies included in the meta- therefore, vigorous activity should beindividuals with CVD (125,145). analysis of effects of exercise interventions avoided in the presence of ketosis. How- on glycemic control (146) had a mean ever, it is not necessary to postpone exer-Reimbursement for MNT number of sessions per week of 3.4, with cise based simply on hyperglycemia,MNT, when delivered by a registered dietitian a mean of 49 min/session. The DPP life- provided the patient feels well and urineaccording to nutrition practice guidelines, is style intervention, which included 150 and/or blood ketones are negative.reimbursedaspartoftheMedicareprogramas min/week of moderate intensity exercise, Hypoglycemia. In individuals taking in-overseen by the Centers for Medicare and had a beneficial effect on glycemia in sulin and/or insulin secretagogues, phys-MedicaidServices(CMS)(www.cms.hhs.gov/ those with prediabetes. Therefore, it ical activity can cause hypoglycemia ifmedicalnutritiontherapy). seems reasonable to recommend that peo- medication dose or carbohydrate con- ple with diabetes try to follow the physical sumption is not altered. For individualsG. Physical activity activity guidelines for the general popula- on these therapies, added carbohydrate tion. should be ingested if pre-exercise glucoseRecommendations Progressive resistance exercise im- levels are 100 mg/dl (5.6 mmol/l). Hy-● People with diabetes should be advised proves insulin sensitivity in older men poglycemia is rare in diabetic individuals to perform at least 150 min/week of with type 2 diabetes to the same or even a who are not treated with insulin or insulin moderate-intensity aerobic physical ac- greater extent as aerobic exercise (150). secretagogues, and no preventive mea- tivity (50 –70% of maximum heart Clinical trials have provided strong evi- sures for hypoglycemia are usually ad- rate). (A) dence for the A1C-lowering value of re- vised in these cases.● In the absence of contraindications, sistance training in older adults with type people with type 2 diabetes should be 2 diabetes (151,152) and for an additive Exercise in the presence of specific encouraged to perform resistance train- benefit of combined aerobic and resis- long-term complications of diabetes ing three times per week. (A) tance exercise in adults with type 2 diabe- Retinopathy. In the presence of prolifer- tes (153). ative diabetic retinopathy (PDR) or severeExercise is an important part of the diabe- nonproliferative diabetic retinopathytes management plan. Regular exercise Evaluation of the diabetic patient (NPDR), vigorous aerobic or resistancehas been shown to improve blood glucose before recommending an exercise exercise may be contraindicated becausecontrol, reduce cardiovascular risk fac- program of the risk of triggering vitreous hemor-tors, contribute to weight loss, and im- Prior guidelines suggested that before rec- rhage or retinal detachment (156).prove well-being. Furthermore, regular ommending a program of physical activ- Peripheral neuropathy. Decreased painexercise may prevent type 2 diabetes in ity, the provider should assess patients sensation in the extremities results in in-S24 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementcreased risk of skin breakdown and infec- Psychological and social problems can barriers including income, health literacy,tion and of Charcot joint destruction. impair the individual’s (162–165) or fam- diabetes distress, depression, and com-Prior recommendations have advised ily’s ability to carry out diabetes care tasks peting demands, including those relatednon–weight-bearing exercise for patients and therefore compromise health status. to family responsibilities and dynamics.with severe peripheral neuropathy. How- There are opportunities for the clinician Other strategies may include culturallyever, studies have shown that moderate- to assess psychosocial status in a timely appropriate and enhanced DSME, co-intensity walking may not lead to and efficient manner so that referral for management with a diabetes team, refer-increased risk of foot ulcers or re- appropriate services can be accom- ral to a medical social worker forulceration in those with peripheral neu- plished. assistance with insurance coverage, orropathy (157). All individuals with Key opportunities for screening of change in pharmacological therapy. Initi-peripheral neuropathy should wear psychosocial status occur at diagnosis, ation of or increase in SMBG, utilizationproper footwear and examine their feet during regularly scheduled management of CGM, frequent contact with the pa-daily to detect lesions early. Anyone with visits, during hospitalizations, at discov- tient, or referral to a mental health profes-a foot injury or open sore should be re- ery of complications, or when problems sional or physician with special expertisestricted to non–weight-bearing activities. with glucose control, quality of life, or ad- in diabetes may be useful. Providing pa-Autonomic neuropathy. Autonomic neu- herence are identified. Patients are likely tients with an algorithm for self-titrationropathy can increase the risk of exercise- to exhibit psychological vulnerability at of insulin doses based on SMBG resultsinduced injury or adverse event through diagnosis and when their medical status may be helpful for type 2 patients whodecreased cardiac responsiveness to exer- changes, e.g., the end of the honeymoon take insulin (172).cise, postural hypotension, impaired period, when the need for intensifiedthermoregulation, impaired night vision treatment is evident, and when complica- J. Hypoglycemiadue to impaired papillary reaction, and tions are discovered (164).unpredictable carbohydrate delivery from Issues known to impact self- Recommendationsgastroparesis predisposing to hypoglyce- management and health outcomes in- ● Glucose (15–20 g) is the preferredmia (158). Autonomic neuropathy is also clude but are not limited to: attitudes treatment for the conscious individualstrongly associated with CVD in people about the illness, expectations for medical with hypoglycemia, although any formwith diabetes (159,160). People with di- management and outcomes, affect/mood, of carbohydrate that contains glucoseabetic autonomic neuropathy should un- general and diabetes-related quality of may be used. If SMBG 15 min afterdergo cardiac investigation before life, diabetes-related distress (166), re- treatment shows continued hypoglyce-beginning physical activity more intense sources (financial, social, and emotional) mia, the treatment should be repeated.than that to which they are accustomed. (167), and psychiatric history (168 – Once SMBG glucose returns to normal,Albuminuria and nephropathy. Physical 170). Screening tools are available for a the individual should consume a mealactivity can acutely increase urinary pro- number of these areas (105). Indications or snack to prevent recurrence of hypo-tein excretion. However, there is no evi- for referral to a mental health specialist glycemia. (E)dence that vigorous exercise increases the familiar with diabetes management may ● Glucagon should be prescribed for allrate of progression of diabetic kidney dis- include: gross noncompliance with med- individuals at significant risk of severeease, and there is likely no need for any ical regimen (by self or others) (170), de- hypoglycemia, and caregivers or familyspecific exercise restrictions for people pression with the possibility of self-harm, members of these individuals should bewith diabetic kidney disease (161). debilitating anxiety (alone or with depres- instructed in its administration. Gluca- sion), indications of an eating disorder gon administration is not limited to (171), or cognitive functioning that health care professionals. (E)H. Psychosocial assessment and care significantly impairs judgment. It is ● Individuals with hypoglycemia un- preferable to incorporate psychological awareness or one or more episodes of assessment and treatment into routine severe hypoglycemia should be advisedRecommendations care rather than waiting for identification to raise their glycemic targets to strictly● Assessment of psychological and social of a specific problem or deterioration in avoid further hypoglycemia for at least situation should be included as an on- psychological status (105). Although the several weeks, to partially reverse hypo- going part of the medical management clinician may not feel qualified to treat glycemia unawareness and reduce risk of diabetes. (E) psychological problems, utilizing the pa- of future episodes. (B)● Psychosocial screening and follow-up tient-provider relationship as a founda- should include, but is not limited to, tion for further treatment can increase the Hypoglycemia is the leading limiting fac- attitudes about the illness, expectations likelihood that the patient will accept re- tor in the glycemic management of type 1 for medical management and out- ferral for other services. It is important to and insulin-treated type 2 diabetes (173). comes, affect/mood, general and diabe- establish that emotional well-being is part Mild hypoglycemia may be inconvenient tes-related quality of life, resources of diabetes management. or frightening to patients with diabetes, (financial, social, and emotional), and and more severe hypoglycemia can cause psychiatric history. (E) I. When treatment goals are not met acute harm to the person with diabetes or● Screen for psychosocial problems such For a variety of reasons, some people with others, if it causes falls, motor vehicle ac- as depression and diabetes-related dis- diabetes and their health care providers cidents, or other injury. A large cohort tress, anxiety, eating disorders, and do not achieve the desired goals of treat- study suggested that among older adults cognitive impairment when self- ment (Table 10). Re-thinking the treat- with type 2 diabetes, a history of severe management is poor. (C) ment regimen may require assessment of hypoglycemia was associated with greatercare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S25
    • Standards of Medical Carerisk of dementia (174). Conversely, evi- K. Intercurrent illness and lifestyle therapy as the comparator.dence from the DCCT/EDIC trial, which The stress of illness, trauma, and/or sur- (E)involved younger type 1 patients, sug- gery frequently aggravates glycemic con-gested no association of frequency of se- trol and may precipitate diabetic Gastric reduction surgery, either gastricvere hypoglycemia with cognitive decline ketoacidosis (DKA) or nonketotic hyper- banding or procedures that involve by-(175). Treatment of hypoglycemia osmolar state, life-threatening conditions passing, transposing, or resecting sections(plasma glucose 70 mg/dl) requires in- that require immediate medical care to of the small intestine, when part of a com-gestion of glucose- or carbohydrate- prevent complications and death. Any prehensive team approach, can be an ef-containing foods. The acute glycemic condition leading to deterioration in gly- fective weight loss treatment for severeresponse correlates better with the glu- cemic control necessitates more frequent obesity, and national guidelines supportcose content than with the carbohydrate monitoring of blood glucose and (in ke- its consideration for people with type 2content of the food. Although pure glu- tosis-prone patients) urine or blood ke- diabetes who have BMI exceeding 35 kg/cose is the preferred treatment, any form tones. Marked hyperglycemia requires m2. Bariatric surgery has been shown toof carbohydrate that contains glucose will temporary adjustment of the treatment lead to near- or complete normalization of program and, if accompanied by ketosis, glycemia in 55–95% of patients withraise blood glucose. Added fat may retard vomiting, or alteration in level of con- type 2 diabetes, depending on the surgicaland then prolong the acute glycemic re- sciousness, immediate interaction with procedure. A meta-analysis of studies ofsponse. Ongoing activity of insulin or in- the diabetes care team. The patient treated bariatric surgery involving 3,188 patientssulin secretagogues may lead to with noninsulin therapies or MNT alone with diabetes reported that 78% had re-recurrence of hypoglycemia unless fur- may temporarily require insulin. Ade- mission of diabetes (normalization ofther food is ingested after recovery. quate fluid and caloric intake must be as- blood glucose levels in the absence of Severe hypoglycemia (where the indi- sured. Infection or dehydration are more medications), and that the remission ratesvidual requires the assistance of another likely to necessitate hospitalization of the were sustained in studies that had fol-person and cannot be treated with oral person with diabetes than the person low-up exceeding 2 years (177). Remis-carbohydrate due to confusion or uncon- without diabetes. sion rates tend to be lower withsciousness) should be treated using emer- The hospitalized patient should be procedures that only constrict the stom-gency glucagon kits, which require a treated by a physician with expertise in ach, and higher with those that bypassprescription. Those in close contact with, the management of diabetes. For further portions of the small intestine. Addition-or having custodial care of, people with information on management of patients ally, there is a suggestion that intestinalhypoglycemia-prone diabetes (family with hyperglycemia in the hospital, see bypass procedures may have glycemic ef-members, roommates, school personnel, VIII.A. Diabetes care in the hospital. For fects that are independent of their effectschild care providers, correctional institu- further information on management of on weight, perhaps involving the incretintion staff, or coworkers), should be in- DKA or nonketotic hyperosmolar state, axis.structed in use of such kits. An individual refer to the ADA consensus statement on One randomized controlled trialdoes not need to be a health care profes- hyperglycemic crises (172). compared adjustable gastric banding tosional to safely administer glucagon. Care “best available” medical and lifestyle ther-should be taken to ensure that unexpired L. Bariatric surgery apy in subjects with type 2 diabetes diag-glucagon kits are available. nosed less than 2 years before Prevention of hypoglycemia is a crit- Recommendations randomization and BMI 30 – 40 kg/m2 ● Bariatric surgery may be considered for (178). In this trial, 73% of surgicallyical component of diabetes management.Teaching people with diabetes to balance adults with BMI 35 kg/m2 and type 2 treated patients achieved “remission” ofinsulin use, carbohydrate intake, and ex- diabetes, especially if the diabetes or as- their diabetes, compared with 13% ofercise is a necessary but not always suffi- sociated comorbidities are difficult to those treated medically. The latter groupcient strategy. In type 1 diabetes and control with lifestyle and pharmaco- lost only 1.7% of body weight, suggesting logic therapy. (B) that their therapy was not optimal. Over-severely insulin-deficient type 2 diabetes, ● Patients with type 2 diabetes who have all the trial had 60 subjects, and only 13the syndrome of hypoglycemia unaware- undergone bariatric surgery need life- had a BMI under 35 kg/m2, making it dif-ness, or hypoglycemia-associated auto- long lifestyle support and medical ficult to generalize these results widely tonomic failure, can severely compromise monitoring. (E) diabetic patients who are less severelystringent diabetes control and quality of ● Although small trials have shown gly- obese or with longer duration of diabetes.life. The deficient counterregulatory hor- cemic benefit of bariatric surgery in pa- In a more recent study involving 110 pa-mone release and autonomic responses in tients with type 2 diabetes and BMI of tients with type 2 diabetes and a meanthis syndrome are both risk factors for, 30 –35 kg/m2, there is currently insuf- BMI of 47 kg/m2, Roux-en-Y gastric by-and caused by, hypoglycemia. A corollary ficient evidence to generally recom- pass resulted in a mean loss of excessto this “vicious cycle” is that several weeks mend surgery in patients with BMI 35 weight of 63% at 1 year and 84% at 2of avoidance of hypoglycemia has been kg/m2 outside of a research protocol. years (179).demonstrated to improve counterregula- (E) Bariatric surgery is costly in the shorttion and awareness to some extent in ● The long-term benefits, cost- term and has some risks. Rates of morbid-many patients (176). Hence, patients with effectiveness, and risks of bariatric sur- ity and mortality directly related to theone or more episodes of severe hypogly- gery in individuals with type 2 diabetes surgery have been reduced considerablycemia may benefit from at least short- should be studied in well-designed in recent years, with 30-day mortalityterm relaxation of glycemic targets. controlled trials with optimal medical rates now 0.28%, similar to those of lapa-S26 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementroscopic cholecystectomy (180). Longer- Safe and effective vaccines are avail- Goalsterm concerns include vitamin and able that can greatly reduce the risk of ● A goal systolic blood pressure 130mineral deficiencies, osteoporosis, and serious complications from these diseases mmHg is appropriate for most patientsrare but often severe hypoglycemia from (186,187). In a case-control series, influ- with diabetes. (C)insulin hypersecretion. Cohort studies at- enza vaccine was shown to reduce diabe- ● Based on patient characteristics and re-tempting to match subjects suggest that tes-related hospital admission by as much sponse to therapy, higher or lower sys-the procedure may reduce longer-term as 79% during flu epidemics (186). There tolic blood pressure targets may bemortality rates (181), and it is reasonable is sufficient evidence to support that peo- appropriate. (B)to postulate that there may be recouping ple with diabetes have appropriate sero- ● Patients with diabetes should be treatedof costs over the long run. Recent retro- logic and clinical responses to these to a diastolic blood pressure 80spective analyses and modeling studies vaccinations. The Centers for Disease mmHg. (B)suggest that these procedures may be cost Control and Prevention (CDC) Advisoryeffective, when one considers reduction Committee on Immunization Practicesin subsequent health care costs (182– recommends influenza and pneumococ- Treatment ● Patients with a systolic blood pressure184). However, studies of the mecha- cal vaccines for all individuals with diabe-nisms of glycemic improvement and tes (http://www.cdc.gov/vaccines/recs/). of 130 –139 mmHg or a diastolic bloodlong-term benefits and risks of bariatric pressure of 80 – 89 mmHg may be givensurgery in individuals with type 2 diabe- lifestyle therapy alone for a maximumtes, especially those who are not severely VI. PREVENTION AND of 3 months and then, if targets are notobese, will require well-designed clinical MANAGEMENT OF achieved, be treated with addition oftrials, with optimal medical and lifestyle DIABETES COMPLICATIONS pharmacological agents. (E) ● Patients with more severe hypertensiontherapy of diabetes and cardiovascularrisk factors as the comparator. A. CVD (systolic blood pressure 140 or dia- CVD is the major cause of morbidity and stolic blood pressure 90 mmHg) atM. Immunization mortality for individuals with diabetes, diagnosis or follow-up should receive and the largest contributor to the direct pharmacologic therapy in addition toRecommendations and indirect costs of diabetes. The com- lifestyle therapy. (A)● Annually provide an influenza vaccine mon conditions coexisting with type 2 ● Lifestyle therapy for hypertension con- to all diabetic patients at least 6 months diabetes (e.g., hypertension and dyslipi- sists of: weight loss, if overweight; Di- of age. (C) demia) are clear risk factors for CVD, and etary Approaches to Stop Hypertension● Administer pneumococcal polysaccha- diabetes itself confers independent risk. (DASH)-style dietary pattern including ride vaccine to all diabetic patients 2 Numerous studies have shown the effi- reducing sodium and increasing potas- years of age. A one-time revaccination is cacy of controlling individual cardiovas- sium intake; moderation of alcohol in- recommended for individuals 64 cular risk factors in preventing or slowing take; and increased physical activity. years of age previously immunized CVD in people with diabetes. Large ben- (B) when they were 65 years of age if the efits are seen when multiple risk factors ● Pharmacologic therapy for patients vaccine was administered 5 years are addressed globally (188,189). Risk for with diabetes and hypertension should ago. Other indications for repeat vacci- coronary heart disease (CHD) and for be with a regimen that includes either nation include nephrotic syndrome, CVD in general can be estimated using an ACE inhibitor or an ARB. If one class chronic renal disease, and other immu- multivariable risk factor approaches, and is not tolerated, the other should be nocompromised states, such as after such a strategy may be desirable to under- substituted. If needed to achieve blood transplantation. (C) take in adult patients prior to instituting pressure targets, a thiazide diuretic preventive therapy. should be added to those with an esti-Influenza and pneumonia are common, mated GFR (eGFR) (see below) 30preventable infectious diseases associated ml/min/1.73 m2 and a loop diuretic for 1. Hypertension/blood pressure those with an eGFR 30 ml/min/1.73with high mortality and morbidity in the control m2. (C)elderly and in people with chronic dis-eases. Though there are limited studies ● Multiple drug therapy (two or morereporting the morbidity and mortality of Recommendations agents at maximal doses) is generallyinfluenza and pneumococcal pneumonia required to achieve blood pressure tar-specifically in people with diabetes, ob- gets. (B)servational studies of patients with a vari- Screening and diagnosis ● If ACE inhibitors, ARBs, or diuretics areety of chronic illnesses, including ● Blood pressure should be measured at used, kidney function and serum potas-diabetes, show that these conditions are every routine diabetes visit. Patients sium levels should be monitored. (E)associated with an increase in hospitaliza- found to have systolic blood pressure ● In pregnant patients with diabetes andtions for influenza and its complications. 130 mmHg or diastolic blood pres- chronic hypertension, blood pressurePeople with diabetes may be at increased sure 80 mmHg should have blood target goals of 110 –129/65–79 mmHgrisk of the bacteremic form of pneumo- pressure confirmed on a separate day. are suggested in the interest of long-coccal infection and have been reported Repeat systolic blood pressure 130 term maternal health and minimizingto have a high risk of nosocomial bactere- mmHg or diastolic blood pressure 80 impaired fetal growth. ACE inhibitorsmia, which has a mortality rate as high as mmHg confirms a diagnosis of hyper- and ARBs are contraindicated during50% (185). tension. (C) pregnancy. (E)care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S27
    • Standards of Medical CareHypertension is a common comorbidity mmHg in the intensive group and 133/70 Only the ACCORD blood pressureof diabetes, affecting the majority of pa- mmHg in the standard group; the differ- trial formally has examined treatment tar-tients, with prevalence depending on type ence achieved was attained with an aver- gets 130 mmHg in diabetes. It is possi-of diabetes, age, obesity, and ethnicity. age of 3.4 medications per participant in ble that lowering systolic blood pressureHypertension is a major risk factor for the intensive group and 2.1 in the stan- from the low-130s to less than 120 mmHgboth CVD and microvascular complica- dard therapy group. The primary out- does not further reduce coronary eventstions. In type 1 diabetes, hypertension is come was a composite of nonfatal MI, or death, and that most of the benefit fromoften the result of underlying nephropa- nonfatal stroke, and CVD death; the haz- lowering blood pressure is achieved bythy, while in type 2 diabetes it usually ard ratio for the primary end point in the targeting a goal of 140 mmHg. How-coexists with other cardiometabolic risk intensive group was 0.88 (95% CI 0.73– ever, this has not been formally assessed.factors. 1.06; P 0.20). Of the prespecified sec- The absence of significant harm, the ondary end points, only stroke and trends toward benefit in stroke, and theScreening and diagnosis nonfatal stroke were statistically signifi- potential heterogeneity with respect to in-Measurement of blood pressure in the of- cantly reduced by intensive blood pres- tensive glycemia management suggestsfice should be done by a trained individ- sure treatment, with a hazard ratio of 0.59 that previously recommended targets areual and should follow the guidelines (95% CI 0.39 – 0.89, P 0.01) and 0.63 reasonable pending further analyses andestablished for nondiabetic individuals: (95% CI 0.41– 0.96, P 0.03), respec- results. Systolic blood pressure targetsmeasurement in the seated position, with tively. If this finding is real, the number more or less stringent than 130 mmHgfeet on the floor and arm supported at needed to treat to prevent one stroke over may be appropriate for individual pa-heart level, after 5 min of rest. Cuff size the course of 5 years with intensive blood tients, based on response to therapy,should be appropriate for the upper arm pressure management is 89. medication tolerance, and individualcircumference. Elevated values should be In predefined subgroup analyses, characteristics, keeping in mind that mostconfirmed on a separate day. Because of there was a suggestion of heterogeneity analyses have suggested that outcomesthe clear synergistic risks of hypertension (P 0.08) based on whether participants are worse if the systolic blood pressure isand diabetes, the diagnostic cut-off for a were randomized to standard or intensive 140 mmHg.diagnosis of hypertension is lower in peo- glycemia intervention. In those random-ple with diabetes (blood pressure 130/ ized to standard glycemic control, the Treatment strategies80) than those without diabetes (blood event rate for the primary end point was Although there are no well-controlledpressure 140/90 mmHg) (190). 1.89 per year in the intensive blood pres- studies of diet and exercise in the treat- Home blood pressure self-monitoring sure arm and 2.47 in the standard blood ment of hypertension in individuals withand 24-h ambulatory blood pressure pressure arm, while the respective rates in diabetes, the Dietary Approaches tomonitoring may provide additional evi- the intensive glycemia arm were 1.85 and Stop Hypertension (DASH) study indence of “white coat” and masked hyper- 1.73. If this observation is true, it suggests nondiabetic individuals has shown anti-tension and other discrepancies between that intensive management to a systolic hypertensive effects similar to pharmaco-office and “true” blood pressure, and in blood pressure target of 120 mmHg logic monotherapy. Lifestyle therapystudies in nondiabetic populations, home may be of benefit in those who are not consists of reducing sodium intake (tomeasurements may better correlate with targeting an A1C of 6% and/or that the 1,500 mg/day) and excess body weight;CVD risk than office measurements benefit of intensive blood pressure man- increasing consumption of fruits, vegeta-(191,192). However, the preponderance agement is diminished by more intensive bles (8 –10 servings/day), and low-fatof the clear evidence of benefits of treat- glycemia management targeting an A1C dairy products (2–3 servings/day); avoid-ment of hypertension in people with dia- of 6%. ing excessive alcohol consumption (nobetes is based on office measurements. Other recent randomized trial data more than 2 servings/day in men and no include those from ADVANCE, in which more than 1 serving/day in women)Treatment goals treatment with an angiotensin-converting (201); and increasing activity levelsEpidemiologic analyses show that blood enzyme inhibitor and a thiazide-type di- (190). These nonpharmacological strate-pressure values 115/75 mmHg are asso- uretic reduced the rate of death but not gies may also positively affect glycemiaciated with increased cardiovascular the composite macrovascular outcome. and lipid control. Their effects on cardio-event rates and mortality in individuals However, the ADVANCE trial had no vascular events have not been established.with diabetes (190,193,194). Random- specified targets for the randomized com- An initial trial of nonpharmacologic ther-ized clinical trials have demonstrated the parison, and the mean systolic blood apy may be reasonable in diabetic individ-benefit (reduction in CHD events, stroke, pressure in the intensive group (135 uals with mild hypertension (systolicand nephropathy) of lowering blood mmHg) was not as low as the mean sys- blood pressure 130 –139 mmHg or dia-pressure to 140 mmHg systolic and tolic blood pressure in the ACCORD stan- stolic blood pressure 80 – 89 mmHg). If 80 mmHg diastolic in individuals with dard therapy group (199). A post hoc systolic blood pressure is 140 mmHgdiabetes (190,195–197). The ACCORD analysis of blood pressure control in and/or diastolic is 90 mmHg at the timetrial examined whether lowering blood 6,400 patients with diabetes and CAD of diagnosis, pharmacologic therapypressure to a systolic 120 mmHg pro- enrolled in the International Verapamil- should be initiated along with nonphar-vides greater cardiovascular protection Trandolapril (INVEST) trial demonstrated macologic therapy (190).than a systolic blood pressure level of that “tight control” ( 130 mmHg) was Lowering of blood pressure with reg-130 –140 mmHg in patients with type 2 not associated with improved CV out- imens based on a variety of antihyperten-diabetes at high risk for CVD (198). The comes compared with “usual care” (130 – sive drugs, including ACE inhibitors,blood pressure achieved was 119/64 140 mmHg) (200). ARBs, -blockers, diuretics, and calciumS28 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementchannel blockers, has been shown to be especially diabetic patients whose targets 40 years), statin therapy should be con-effective in reducing cardiovascular are lower. Many patients will require sidered in addition to lifestyle therapy ifevents. Several studies suggested that three or more drugs to reach target goals LDL cholesterol remains above 100ACE inhibitors may be superior to dihy- (190). If blood pressure is refractory to mg/dl or in those with multiple CVDdropyridine calcium channel blockers in optimal doses of at least three antihyper- risk factors. (E)reducing cardiovascular events (202– tensive agents of different classifications, ● In individuals without overt CVD, the204). However, a variety of other studies one of which should be a diuretic, clini- primary goal is an LDL cholesterolhave shown no specific advantage to ACE cians should consider an evaluation for 100 mg/dl (2.6 mmol/l). (A)inhibitors as initial treatment of hyperten- secondary forms of hypertension. ● In individuals with overt CVD, a lowersion in the general hypertensive popula- During pregnancy in diabetic women LDL cholesterol goal of 70 mg/dl (1.8tion, but rather an advantage on with chronic hypertension, target blood mmol/l), using a high dose of a statin, iscardiovascular outcomes of initial therapy pressure goals of systolic blood pressure an option. (B)with low-dose thiazide diuretics 110 –129 mmHg and diastolic blood ● If drug-treated patients do not reach the(190,205,206). pressure 65–79 mmHg are reasonable, as above targets on maximal tolerated sta- In people with diabetes, inhibitors of they contribute to long-term maternal tin therapy, a reduction in LDL choles-the renin-angiotensin system (RAS) may health. Lower blood pressure levels may terol of 30 – 40% from baseline is anhave unique advantages for initial or early be associated with impaired fetal growth. alternative therapeutic goal. (A)therapy of hypertension. In a nonhyper- During pregnancy, treatment with ACE ● Triglyceride levels 150 mg/dl (1.7tension trial of high-risk individuals, in- inhibitors and ARBs is contraindicated, mmol/l) and HDL cholesterol 40cluding a large subset with diabetes, an since they can cause fetal damage. Anti- mg/dl (1.0 mmol/l) in men and 50ACE inhibitor reduced CVD outcomes hypertensive drugs known to be effective mg/dl (1.3 mmol/l) in women, are de-(207). In patients with congestive heart and safe in pregnancy include methyl- sirable. However, LDL cholesterol–failure (CHF), including diabetic sub- dopa, labetalol, diltiazem, clonidine, and targeted statin therapy remains thegroups, ARBs have been shown to reduce prazosin. Chronic diuretic use during preferred strategy. (C)major CVD outcomes (208 –211), and in pregnancy has been associated with re- ● If targets are not reached on maximallytype 2 patients with significant nephrop- stricted maternal plasma volume, which tolerated doses of statins, combinationathy, ARBs were superior to calcium might reduce uteroplacental perfusion therapy using statins and other lipid-channel blockers for reducing heart fail- (213). lowering agents may be considered toure (212). Though evidence for distinct achieve lipid targets but has not beenadvantages of RAS inhibitors on CVD out- 2. Dyslipidemia/lipid management evaluated in outcome studies for eithercomes in diabetes remains conflicting CVD outcomes or safety. (E)(195,206), the high CVD risks associated Recommendations ● Statin therapy is contraindicated inwith diabetes, and the high prevalence of pregnancy. (E)undiagnosed CVD, may still favor recom- Screeningmendations for their use as first-line hy- ● In most adult patients, measure fasting Evidence for benefits of lipid-pertension therapy in people with lipid profile at least annually. In adults lowering therapydiabetes (190). Recently, the blood pres- with low-risk lipid values (LDL choles- Patients with type 2 diabetes have an in-sure arm of the ADVANCE trial demon- terol 100 mg/dl, HDL cholesterol creased prevalence of lipid abnormalities,strated that routine administration of a 50 mg/dl, and triglycerides 150 contributing to their high risk of CVD.fixed combination of the ACE inhibitor mg/dl), lipid assessments may be re- For the past decade or more, multipleperindopril and the diuretic indapamide peated every 2 years. (E) clinical trials demonstrated significant ef-significantly reduced combined micro- fects of pharmacologic (primarily statin)vascular and macrovascular outcomes, as Treatment recommendations and therapy on CVD outcomes in subjectswell as CVD and total mortality. The im- goals with CHD and for primary CVD preven-proved outcomes could also have been ● Lifestyle modification focusing on the tion (214). Sub-analyses of diabetic sub-due to lower achieved blood pressure in reduction of saturated fat, trans fat, and groups of larger trials (215–219) andthe perindopril-indapamide arm (199). cholesterol intake; increase of omega-3 trials specifically in subjects with diabetesIn addition, the Avoiding Cardiovascular fatty acids, viscous fiber, and plant (220,221) showed significant primaryEvents through Combination Therapy in stanols/sterols; weight loss (if indi- and secondary prevention of CVDPatients Living with Systolic Hyperten- cated); and increased physical activity events CHD deaths in diabetic popula-sion (ACCOMPLISH) trial showed a de- should be recommended to improve tions. As shown in Table 11, and similarcrease in morbidity and mortality in those the lipid profile in patients with diabe- to findings in nondiabetic subjects, re-receiving benazapril and amlodipine ver- tes. (A) duction in “hard” CVD outcomes (CHDsus benazapril and hydrochlorothiazide. ● Statin therapy should be added to life- death and nonfatal MI) can be moreThe compelling benefits of RAS inhibitors style therapy, regardless of baseline clearly seen in diabetic subjects with highin diabetic patients with albuminuria or lipid levels, for diabetic patients: baseline CVD risk (known CVD and/orrenal insufficiency provide additional ra- ● with overt CVD. (A) very high LDL cholesterol levels), buttionale for use of these agents (see VI.B. ● without CVD who are over age 40 overall the benefits of statin therapy inNephropathy screening and treatment). years and have one or more other people with diabetes at moderate or high An important caveat is that most pa- CVD risk factors. (A) risk for CVD are convincing.tients with hypertension require multi- ● For patients at lower risk than above Low levels of HDL cholesterol, oftendrug therapy to reach treatment goals, (e.g., without overt CVD and under age associated with elevated triglyceride lev-care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S29
    • Standards of Medical CareTable 11—Reduction in 10-year risk of major CVD endpoints (CHD death/non-fatal MI) in major statin trials, or substudies of major trials,in diabetic subjects (n 16,032) Statin dose and Risk Relative risk Absolute risk LDL cholesterol LDL cholesterolStudy (ref.) CVD comparator reduction (%) reduction (%) reduction (%) reduction (mg/dl) reduction (%)4S-DM (215) 2° Simvastatin 20–40 mg 85.7 to 43.2 50 42.5 186 to 119 36 vs. placeboASPEN 2° (220) 2° Atorvastatin 10 mg vs. 39.5 to 24.5 34 15 112 to 79 29 placeboHPS-DM (216) 2° Simvastatin 40 mg vs. 43.8 to 36.3 17 7.5 123 to 84 31 placeboCARE-DM (217) 2° Pravastatin 40 mg vs. 40.8 to 35.4 13 5.4 136 to 99 27 placeboTNT-DM (218) 2° Atorvastatin 80 mg vs. 26.3 to 21.6 18 4.7 99 to 77 22 10 mgHPS-DM (216) 1° Simvastatin 40 mg vs. 17.5 to 11.5 34 6.0 124 to 86 31 placeboCARDS (221) 1° Atorvastatin 10 mg vs. 11.5 to 7.5 35 4 118 to 71 40 placeboASPEN 1° (220) 1° Atorvastatin 10 mg vs. 9.8 to 7.9 19 1.9 114 to 80 30 placeboASCOT-DM (219) 1° Atorvastatin 10 mg vs. 11.1 to 10.2 8 0.9 125 to 82 34 placeboStudies were of differing lengths (3.3–5.4 years) and used somewhat different outcomes, but all reported rates of CVD death and nonfatal MI. In this tabulation,results of the statin on 10-year risk of major CVD endpoints (CHD death/nonfatal 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.els, are the most prevalent pattern of dys- urated fat, cholesterol, and trans unsatur- diabetic patients as in type 2 diabetic pa-lipidemia in persons with type 2 diabetes. ated fat intake and increases in omega-3 tients, particularly if they have other car-However, the evidence base for drugs that fatty acids, viscous fiber (such as in oats, diovascular risk factors.target these lipid fractions is significantly legumes, citrus), and plant stanols/less robust than that for statin therapy sterols. Glycemic control can also benefi- Alternative LDL cholesterol goals(222). Nicotinic acid has been shown to cially modify plasma lipid levels, Virtually all trials of statins and CVD out-reduce CVD outcomes (223), although particularly in patients with very high comes tested specific doses of statinsthe study was done in a nondiabetic co- triglycerides and poor glycemic control. against placebo, other doses of statin, orhort. Gemfibrozil has been shown to de- In those with clinical CVD or over age other statins, rather than aiming for spe-crease rates of CVD events in subjects 40 years with other CVD risk factors, cific LDL cholesterol goals (228). As canwithout diabetes (224,225) and in the di- pharmacological treatment should be be seen in Table 11, placebo-controlledabetic subgroup in one of the larger trials added to lifestyle therapy regardless of trials generally achieved LDL cholesterol(224). However, in a large trial specific to baseline lipid levels. Statins are the drugs reductions of 30 – 40% from baseline.diabetic patients, fenofibrate failed to re- of choice for LDL cholesterol lowering. Hence, LDL cholesterol lowering of thisduce overall cardiovascular outcomes In patients other than those described magnitude is an acceptable outcome for(226). above, statin treatment should be consid- patients who cannot reach LDL choles- ered if there is an inadequate LDL choles- terol goals due to severe baseline eleva-Dyslipidemia treatment and target terol response to lifestyle modifications tions in LDL cholesterol and/orlipid levels and improved glucose control, or if the intolerance of maximal, or any, statinFor most patients with diabetes, the first patient has increased cardiovascular risk doses. Additionally for those with base-priority of dyslipidemia therapy (unless (e.g., multiple cardiovascular risk factors line LDL cholesterol minimally above 100severe hypertriglyceridemia is the imme- or long duration of diabetes). Very little mg/dl, prescribing statin therapy to lowerdiate issue) is to lower LDL cholesterol to clinical trial evidence exists for type 2 di- LDL cholesterol about 30 – 40% froma target goal of 100 mg/dl (2.60 mmol/l) abetic patients under age 40 years or for baseline is probably more effective than(227). Lifestyle intervention, including type 1 patients of any age. In the Heart prescribing just enough to get LDL cho-MNT, increased physical activity, weight Protection Study (lower age limit 40 lesterol slightly below 100 mg/dl.loss, and smoking cessation, may allow years), the subgroup of 600 patients with Recent clinical trials in high-risk pa-some patients to reach lipid goals. Nutri- type 1 diabetes had a proportionately sim- tients, such as those with acute coronarytion intervention should be tailored ac- ilar reduction in risk as patients with type syndromes or previous cardiovascularcording to each patient’s age, type of 2 diabetes, although not statistically sig- events (229 –231), have demonstrateddiabetes, pharmacological treatment, nificant (216). Although the data are not that more aggressive therapy with highlipid levels, and other medical conditions definitive, consideration should be given doses of statins to achieve an LDL choles-and should focus on the reduction of sat- to similar lipid-lowering goals in type 1 terol of 70 mg/dl led to a significant re-S30 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementduction in further events. Therefore, a triglyceride levels are accompanied by Table 12—Summary of recommendationsreduction in LDL cholesterol to a goal of only modest changes in glucose that are for glycemic blood pressure and lipid control 70 mg/dl is an option in very-high-risk generally amenable to adjustment of dia- for most adults with diabetesdiabetic patients with overt CVD (232). betes therapy (235,236). A1C 7.0%* In individual patients, LDL choles- Blood pressure 130/80 mmHg†terol lowering with statins is highly vari- Combination therapy Lipidsable, and this variable response is poorly Combination therapy, with a statin and a LDL cholesterol 100 mg/dlunderstood (233). Reduction of CVD fibrate or statin and niacin, may be effica- ( 2.6 mmol/l)‡events with statins correlates very closely cious for treatment for all three lipid frac- *More or less stringent glycemic goals may be ap-with LDL cholesterol lowering (214). tions, but this combination is associated propriate for individual patients. Goals should beWhen maximally tolerated doses of st- with an increased risk for abnormal individualized based on: duration of diabetes, age/atins fail to significantly lower LDL cho- transaminase levels, myositis, or rhabdo- life expectancy, comorbid conditions, known CVDlesterol ( 30% reduction from patients myolysis. The risk of rhabdomyolysis is or advanced microvascular complications, hypogly- cemia unawareness, and individual patient consid-baseline), the primary aim of combination higher with higher doses of statins and erations. †Based on patient characteristics andtherapy should be to achieve additional with renal insufficiency and seems to be response to therapy, higher or lower systolic bloodLDL cholesterol lowering. Niacin, fenofi- lower when statins are combined with fe- pressure targets may be appropriate. ‡In individualsbrate, ezetimibe, and bile acid seques- nofibrate than gemfibrozil (237). In the with overt CVD, a lower LDL cholesterol goal oftrants all offer additional LDL cholesterol 70 mg/dl (1.8 mmol/l), using a high dose of a recent ACCORD study, the combination statin, is an option.lowering. The evidence that combination of fenofibrate and simvastatin did not re-therapy provides a significant increment duce the rate of fatal cardiovascularin CVD risk reduction over statin therapy events, nonfatal myocardial infarction, or multiple other risk factors (e.g., 10-yearalone is still elusive. nonfatal stroke, as compared with simva- risk 5–10%), clinical judgment is re- In 2008, a consensus panel convened statin alone, in patients with type 2 dia- quired. (E)by the American Diabetes Association and betes who were at high risk for CVD. ● Use aspirin therapy (75–162 mg/day)the American College of Cardiology rec- However, prespecified subgroup analyses as a secondary prevention strategy inommended a greater focus on non-HDL suggested heterogeneity in treatment ef- those with diabetes with a history ofcholesterol and apo lipoprotein B (apo B) fects according to sex, with a benefit for CVD. (A)in patients who are likely to have small men and possible harm for women, and a ● For patients with CVD and docu-LDL particles, such as people with diabe- possible benefit of combination therapy mented aspirin allergy, clopidogrel (75tes (234). The consensus panel suggested for patients with both triglyceride level mg/day) should be used. (B)that for statin-treated patients in whom 204 mg/dl and HDL cholesterol level ● Combination therapy with ASA (75–the LDL cholesterol goal would be 70 34 mg/dl (238). Other ongoing trials 162 mg/day) and clopidogrel (75 mg/mg/dl (non-HDL cholesterol 100 mg/ may provide much-needed evidence for day) is reasonable for up to a year afterdl), apo B should be measured and treated the effects of combination therapy on car- an acute coronary syndrome. (B)to 80 mg/dl. For patients on statins with diovascular outcomes.an LDL cholesterol goal of 100 mg/dl ADA and the American Heart Association(non-HDL cholesterol 130 mg/dl), apo Table 12 summarizes common treatment (AHA) have, in the past, jointly recom-B should be measured and treated to 90 goals for A1C, blood pressure, and HDL mended that low-dose aspirin therapy bemg/dl. cholesterol. used as a primary prevention strategy in those with diabetes at increased cardio-Treatment of other lipoprotein 3. Antiplatelet agents vascular risk, including those who arefractions or targets over 40 years of age or those with addi-Severe hypertriglyceridemia may warrant Recommendations tional risk factors (family history of CVD,immediate therapy of this abnormality ● Consider aspirin therapy (75–162 mg/ hypertension, smoking, dyslipidemia, orwith lifestyle and usually pharmacologic day) as a primary prevention strategy in albuminuria) (188). These recommenda-therapy (fibric acid derivative, niacin, or those with type 1 or type 2 diabetes at tions were derived from several older tri-fish oil) to reduce the risk of acute pan- increased cardiovascular risk (10-year als that included small numbers ofcreatitis. In the absence of severe hyper- risk 10%). This includes most men patients with diabetes.triglyceridemia, therapy targeting HDL 50 years of age or women 60 years Aspirin has been shown to be effec-cholesterol or triglycerides has intuitive of age who have at least one additional tive in reducing cardiovascular morbidityappeal but lacks the evidence base of sta- major risk factor (family history of and mortality in high-risk patients withtin therapy. If the HDL cholesterol is 40 CVD, hypertension, smoking, dyslipi- previous myocardial infarction or strokemg/dl and the LDL cholesterol between demia, or albuminuria). (C) (secondary prevention). Its net benefit in100 and 129 mg/dl, gemfibrozil or niacin ● Aspirin should not be recommended primary prevention among patients withmight be used, especially if a patient is for CVD prevention for adults with di- no previous cardiovascular events is moreintolerant to statins. Niacin is the most abetes at low CVD risk (10-year CVD controversial, both for patients with andeffective drug for raising HDL cholesterol. risk 5%, such as in men 50 and without a history of diabetes (239). TwoIt can significantly increase blood glucose women 60 years of age with no major recent randomized controlled trials of as-at high doses, but recent studies demon- additional CVD risk factors), since the pirin specifically in patients with diabetesstrate that at modest doses (750 –2,000 potential adverse effects from bleeding failed to show a significant reduction inmg/day), significant improvements in likely offset the potential benefits. (C) CVD end points, raising further questionsLDL cholesterol, HDL cholesterol, and ● In patients in these age-groups with about the efficacy of aspirin for primarycare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S31
    • Standards of Medical Careprevention in people with diabetes demia, family history of premature CVD, and health risks. Much of the work doc-(240,241). and albuminuria. umenting the impact of smoking on The Anti-thrombotic Trialists’ (ATT) However, aspirin is no longer recom- health did not separately discuss resultscollaborators recently published an indi- mended for those at low CVD risk on subsets of individuals with diabetes,vidual patient-level meta-analysis of the (women under age 60 years and men un- but suggests that the identified risks are atsix large trials of aspirin for primary pre- der age 50 years with no major CVD risk least equivalent to those found in the gen-vention in the general population. These factors; 10-year CVD risk under 5%) as eral population. Other studies of individ-trials collectively enrolled over 95,000 the low benefit is likely to be outweighed uals with diabetes consistentlyparticipants, including almost 4,000 with by the risks of significant bleeding. Clin- demonstrate that smokers have a height-diabetes. Overall, they found that aspirin ical judgment should be used for those at ened risk of CVD, premature death, andreduced the risk of vascular events by intermediate risk (younger patients with increased rate of microvascular complica-12% (RR 0.88 [95% CI 0.82– 0.94]). The one or more risk factors, or older patients tions of diabetes. Smoking may have alargest reduction was for nonfatal myo- with no risk factors; those with 10-year role in the development of type 2 diabe-cardial infarction with little effect on CHD CVD risk of 5–10%) until further research tes.death (RR 0.95 [95% CI 0.78 –1.15]) or is available. Use of aspirin in patients un- The routine and thorough assess-total stroke. There was some evidence of a der the age of 21 years is contraindicated ment of tobacco use is important as adifference in aspirin effect by sex. Aspirin due to the associated risk of Reye’s syn- means of preventing smoking or en-significantly reduced CHD events in men drome. couraging cessation. A number of largebut not in women. Conversely, aspirin Average daily dosages used in most randomized clinical trials have demon-had no effect on stroke in men but signif- clinical trials involving patients with dia- strated the efficacy and cost-effective-icantly reduced stroke in women. Nota- betes ranged from 50 to 650 mg but were ness of brief counseling in smokingbly, sex differences in aspirin’s effects mostly in the range of 100 to 325 mg/day. cessation, including the use of quithave not been observed in studies of sec- There is little evidence to support any spe- lines, in the reduction of tobacco use.ondary prevention (239). In the six trials cific dose, but using the lowest possible For the patient motivated to quit, theexamined by the ATT collaborators, the dosage may help reduce side effects addition of pharmacological therapy toeffects of aspirin on major vascular events (244). Although platelets from patients counseling is more effective than eitherwere similar for patients with or without with diabetes have altered function, it is treatment alone. Special considerationsdiabetes: RR 0.88 (95% CI 0.67–1.15) unclear what, if any, impact that finding should include assessment of level of has on the required dose of aspirin for nicotine dependence, which is associ-and 0.87 (0.79 – 0.96), respectively. The cardioprotective effects in the patient ated with difficulty in quitting and re-CI was wider for those with diabetes be- with diabetes. Many alternate pathways lapse (247).cause of their smaller number. for platelet activation exist that are inde- Based on the currently available evi- pendent of thromboxane A2 and thus not 5. CHD screening and treatmentdence, aspirin appears to have a modest sensitive to the effects of aspirin (245).effect on ischemic vascular events with Therefore, while “aspirin resistance” ap- Recommendationsthe absolute decrease in events depending pears higher in the diabetic patients whenon the underlying CVD risk. The main measured by a variety of ex vivo and in Screeningadverse effects appear to be an increased vitro methods (platelet aggrenometry, ● In asymptomatic patients, routinerisk of gastrointestinal bleeding. The ex- measurement of thromboxane B2), these screening for CAD is not recom-cess risk may be as high as 1–5 per 1,000 observations alone are insufficient to em- mended, as it does not improve out-per year in real-world settings. In adults pirically recommend higher doses of as- comes as long as CVD risk factors arewith CVD risk greater than 1% per year, pirin be used in the diabetic patient at this treated. (A)the number of CVD events prevented will time.be similar to or greater than the number of Clopidogrel has been demonstrated Treatmentepisodes of bleeding induced, although to reduce CVD events in diabetic individ- ● In patients with known CVD, ACE in-these complications do not have equal ef- uals (246). It is recommended as adjunc- hibitor (C) and aspirin and statin ther-fects on long-term health (242). tive therapy in the first year after an acute apy (A) (if not contraindicated) should In 2010, a position statement of the coronary syndrome or as alternative ther- be used to reduce the risk of cardiovas-ADA, AHA, and American College of Car- apy in aspirin-intolerant patients. cular events.diology Foundation (ACCF) updated ● In patients with a prior myocardial in-prior joint recommendations for primary 4. Smoking cessation farction, -blockers should be contin-prevention (243). Low dose (75–162 mg/ ued for at least 2 years after the eventday) aspirin use for primary prevention is Recommendations (B).reasonable for adults with diabetes and no ● Advise all patients not to smoke. (A) ● Longer term use of -blockers in theprevious history of vascular disease who ● Include smoking cessation counseling absence of hypertension is reasonable ifare at increased CVD risk (10-year risk of and other forms of treatment as a rou- well tolerated, but data are lacking. (E)CVD events over 10%) and who are not at tine component of diabetes care. (B) ● Avoid TZD treatment in patients withincreased risk for bleeding. This generally symptomatic heart failure. (C)includes most men over age 50 years and A large body of evidence from epidemio- ● Metformin may be used in patients withwomen over age 60 years who also have logical, case-control, and cohort studies stable CHF if renal function is normal.one or more of the following major risk provides convincing documentation of It should be avoided in unstable or hos-factors: smoking, hypertension, dyslipi- the causal link between cigarette smoking pitalized patients with CHF. (C)S32 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementScreening for CAD is reviewed in a re- the modern setting of aggressive CVD minuria, ACE inhibitors have beencently updated consensus statement risk factor control. shown to delay the progression of ne-(154). To identify the presence of CAD In all patients with diabetes, cardio- phropathy. (A)in diabetic patients without clear or vascular risk factors should be assessed ● In patients with type 2 diabetes, hy-suggestive symptoms, a risk factor– at least annually. These risk factors in- pertension, and microalbuminuria,based approach to the initial diagnostic clude dyslipidemia, hypertension, both ACE inhibitors and ARBs haveevaluation and subsequent follow-up smoking, a positive family history of been shown to delay the progressionhas intuitive appeal. However, recent premature coronary disease, and the to macroalbuminuria. (A)studies concluded that using this ap- presence of micro- or macroalbumin- ● In patients with type 2 diabetes, hy-proach fails to identify which patients uria. Abnormal risk factors should be pertension, macroalbuminuria, andwith type 2 diabetes will have silent treated as described elsewhere in these renal insufficiency (serum creatinineischemia on screening tests (159,248). guidelines. Patients at increased CHD 1.5 mg/dl), ARBs have been shown Candidates for cardiac testing in- risk should receive aspirin and a statin to delay the progression of nephrop-clude those with 1) typical or atypical and ACE inhibitor or ARB therapy if hy- athy. (A)cardiac symptoms and 2) an abnormal pertensive, unless there are contraindi- ● If one class is not tolerated, the otherresting ECG. The screening of asymp- cations to a particular drug class. While should be substituted. (E)tomatic patients remains controversial, clear benefit exists for ACE inhibitor ● Reduction of protein intake to 0.8 –1.0especially as intensive medical therapy, and ARB therapy in patients with ne- g kg body wt 1 day 1 in individualsindicated in diabetic patients at high phropathy or hypertension, the benefits with diabetes and the earlier stages ofrisk for CVD, has an increasing evidence in patients with CVD in the absence of CKD and to 0.8 g kg body wt 1base for providing equal outcomes to these conditions is less clear, especially day 1 in the later stages of CKD mayinvasive revascularization, including in when LDL cholesterol is concomitantly improve measures of renal functiondiabetic patients (249,250). There is controlled (256,257). (urine albumin excretion rate, GFR)also some evidence that silent myocar- and is recommended. (B)dial ischemia may reverse over time, B. Nephropathy screening and ● When ACE inhibitors, ARBs, or diuret-adding to the controversy concerning treatment ics are used, monitor serum creatinineaggressive screening strategies (251). and potassium levels for the develop-Finally, a recent randomized observa- Recommendations ment of acute kidney disease and hy-tional trial demonstrated no clinical perkalemia. (E)benefit to routine screening of asymp- General recommendations ● Continued monitoring of urine albu-tomatic patients with type 2 diabetes ● To reduce the risk or slow the progres- min excretion to assess both responseand normal ECGs (252). Despite abnor- sion of nephropathy, optimize glucose to therapy and progression of disease ismal myocardial perfusion imaging in control. (A) recommended. (E)more than one in five patients, cardiac ● To reduce the risk or slow the progres- ● When eGFR 60 ml/min/1.73 m2,outcomes were essentially equal (and sion of nephropathy, optimize blood evaluate and manage potential compli-very low) in screened versus un- pressure control. (A) cations of CKD. (E)screened patients. Accordingly, the ● Consider referral to a physician experi-overall effectiveness, especially the Screening enced in the care of kidney diseasecost-effectiveness, of such an indiscrim- ● Perform an annual test to assess urine when there is uncertainty about the eti-inate screening strategy is now ques- albumin excretion in type 1 diabetic pa- ology of kidney disease (heavy protein-tioned. tients with diabetes duration of 5 years uria, active urine sediment, absence of Newer noninvasive CAD screening and in all type 2 diabetic patients start- retinopathy, rapid decline in GFR), dif-methods, such as computed tomogra- ing at diagnosis. (E) ficult management issues, or advancedphy (CT) and CT angiography have ● Measure serum creatinine at least annu- kidney disease. (B)gained in popularity. These tests infer ally in all adults with diabetes regard-the presence of coronary atherosclerosis less of the degree of urine albuminby measuring the amount of calcium in excretion. The serum creatinine should Diabetic nephropathy occurs in 20 – 40%coronary arteries and, in some circum- be used to estimate GFR and stage the of patients with diabetes and is the singlestances, by direct visualization of lumi- level of chronic kidney disease (CKD), leading cause of end-stage renal diseasenal stenoses. Although asymptomatic if present. (E) (ESRD). Persistent albuminuria in thediabetic patients found to have a higher range of 30 –299 mg/24 h (microalbu-coronary disease burden have more fu- Treatment minuria) has been shown to be the earliestture cardiac events (253–255), the role ● In the treatment of the nonpregnant pa- stage of diabetic nephropathy in type 1of these tests beyond risk stratification tient with micro- or macroalbuminuria, diabetes and a marker for development ofis not clear. Their routine use leads to either ACE inhibitors or ARBs should nephropathy in type 2 diabetes. Mi-radiation exposure and may result in be used. (A) croalbuminuria is also a well-establishedunnecessary invasive testing such as ● While there are no adequate head-to- marker of increased CVD risk (258,259).coronary angiography and revascular- head comparisons of ACE inhibitors Patients with microalbuminuria whoization procedures. The ultimate bal- and ARBs, there is clinical trial support progress to macroalbuminuria (300ance of benefit, cost, and risks of such for each of the following statements: mg/24 h) are likely to progress to ESRDan approach in asymptomatic patients ● In patients with type 1 diabetes, with (260,261). However, a number of inter-remains controversial, particularly in hypertension and any degree of albu- ventions have been demonstrated to re-care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S33
    • Standards of Medical Careduce the risk and slow the progression of Table 13—Definitions of abnormalities in al- one of these diagnostic thresholds. Exer-renal disease. bumin excretion cise within 24 h, infection, fever, CHF, Intensive diabetes management with marked hyperglycemia, and marked hy-the goal of achieving near-normoglyce- Spot collection pertension may elevate urinary albuminmia has been shown in large prospective ( g/mg excretion over baseline values.randomized studies to delay the onset of Category creatinine) Information on presence of abnormalmicroalbuminuria and the progression of urine albumin excretion in addition tomicro- to macroalbuminuria in patients Normal 30 level of GFR may be used to stage CKD.with type 1 (262,263) and type 2 (55,56) Microalbuminuria 30–299 The National Kidney Foundation classifi-diabetes. The UKPDS provided strong ev- Macro (clinical)-albuminuria 300 cation (Table 14) is primarily based onidence that control of blood pressure can GFR levels and therefore differs fromreduce the development of nephropathy other systems, in which staging is based(195). In addition, large prospective ran- rare individual unable to tolerate ACE in- primarily on urinary albumin excretiondomized studies in patients with type 1 hibitors or ARBs. (285). Studies have found decreased GFRdiabetes have demonstrated that achieve- Studies in patients with varying stages in the absence of increased urine albuminment of lower levels of systolic blood of nephropathy have shown that protein excretion in a substantial percentage ofpressure ( 140 mmHg) resulting from restriction of dietary protein helps slow the progression of albuminuria, GFR de- adults with diabetes (286). Serum creati-treatment using ACE inhibitors provides a nine should therefore be measured at leastselective benefit over other antihyperten- cline, and occurrence of ESRD (279 – 282). Dietary protein restriction should annually in all adults with diabetes, re-sive drug classes in delaying the progres- gardless of the degree of urine albuminsion from micro- to macroalbuminuria be considered particularly in patients whose nephropathy seems to be progress- excretion.and can slow the decline in GFR in pa- Serum creatinine should be used totients with macroalbuminuria (264 – ing despite optimal glucose and blood pressure control and use of ACE inhibitor estimate GFR and to stage the level of266). In type 2 diabetes with CKD, if present. eGFR is commonly co-hypertension and normoalbuminuria, and/or ARBs (282). reported by laboratories or can be esti-RAS inhibition has been demonstrated to mated using formulae such as thedelay onset of microalbuminuria (267). Assessment of albuminuria status and renal function Modification of Diet in Renal Disease In addition, ACE inhibitors have been (MDRD) study equation (287). Recent re-shown to reduce major CVD outcomes Screening for microalbuminuria can be performed by measurement of the albu- ports have indicated that the MDRD is(i.e., myocardial infarction, stroke, death) more accurate for the diagnosis and strat-in patients with diabetes (207), thus fur- min-to-creatinine ratio in a random spot collection; 24-h or timed collections are ification of CKD in patients with diabetesther supporting the use of these agents in than the Cockcroft-Gault formula (288).patients with microalbuminuria, a CVD more burdensome and add little to pre- diction or accuracy (283,284). Measure- GFR calculators are available at http://risk factor. ARBs do not prevent mi- ment of a spot urine for albumin only, www.nkdep.nih.gov.croalbuminuria in normotensive patients whether by immunoassay or by using a The role of continued annual quan-with type 1 or type 2 diabetes (268,269); dipstick test specific for microalbumin, titative assessment of albumin excretionhowever, ARBs have been shown to re- without simultaneously measuring urine after diagnosis of microalbuminuria andduce the rate of progression from micro- creatinine, is somewhat less expensive but institution of ACE inhibitor or ARBto macroalbuminuria as well as ESRD inpatients with type 2 diabetes (270 –272). susceptible to false-negative and -positive therapy and blood pressure control isSome evidence suggests that ARBs have a determinations as a result of variation in unclear. Continued surveillance can as-smaller magnitude of rise in potassium urine concentration due to hydration and sess both response to therapy and pro-compared with ACE inhibitors in people other factors. gression of disease. Some suggest thatwith nephropathy (273,274). Combina- Abnormalities of albumin excretion reducing abnormal albuminuria ( 30tions of drugs that block the renin- are defined in Table 13. Because of vari- mg/g) to the normal or near-normalangiotensin-aldosterone system (e.g., an ability in urinary albumin excretion, two range may improve renal and cardiovas-ACE inhibitor plus an ARB, a mineralo- of three specimens collected within a 3- to cular prognosis, but this approach hascorticoid antagonist, or a direct renin in- 6-month period should be abnormal be- not been formally evaluated in prospec-hibitor) have been shown to provide fore considering a patient to have crossed tive trials.additional lowering of albuminuria (275–278). However, the long-term effects of Table 14—Stages of CKDsuch combinations on renal or cardiovas-cular outcomes have not yet been evalu- GFR (ml/min per 1.73 m2ated in clinical trials, and they are Stage Description body surface area)associated with increased risk for hyper-kalemia. 1 Kidney damage* with normal or increased GFR 90 Other drugs, such as diuretics, cal- 2 Kidney damage* with mildly decreased GFR 60–89cium channel blockers, and -blockers 3 Moderately decreased GFR 30–59should be used as additional therapy to 4 Severely decreased GFR 15–29further lower blood pressure in patients 5 Kidney failure 15 or dialysisalready treated with ACE inhibitors or *Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests. Adapted from ref.ARBs (212), or as alternate therapy in the 284.S34 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement Complications of kidney disease cor- Table 15—Management of CKD in diabetesrelate with level of kidney function. Whenthe eGFR is less than 60 ml/min/1.73 m2, GFR (ml/min/screening for complications of CKD is in- 1.73 m2) Recommendeddicated (Table 15). Early vaccinationagainst hepatitis B is indicated in patients All patients Yearly measurement of creatinine, urinary albumin excretion, potassiumlikely to progress to end-stage kidney dis- 45–60 Referral to nephrology if possibility for nondiabetic kidney disease existsease. (duration type 1 diabetes 10 years, heavy proteinuria, abnormal Consider referral to a physician ex- findings on renal ultrasound, resistant hypertension, rapid fall inperienced in the care of kidney disease GFR, or active urinary sediment)when there is uncertainty about the eti- Consider need for dose adjustment of medicationsology of kidney disease (heavy protein- Monitor eGFR every 6 monthsuria, active urine sediment, absence of Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus,retinopathy, rapid decline in GFR, re- parathyroid hormone at least yearlysistant hypertension), difficult manage- Assure vitamin D sufficiencyment issues, or advanced kidney Consider bone density testingdisease. The threshold for referral may Referral for dietary counsellingvary depending on the frequency with 30–44 Monitor eGFR every 3 monthswhich a provider encounters diabetic Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroidpatients with significant kidney disease. hormone, hemoglobin, albumin, weight every 3–6 monthsConsultation with a nephrologist when Consider need for dose adjustment of medicationsstage 4 CKD develops has been found to 30 Referral to nephrologistreduce cost, improve quality of care, Adapted from http://www.kidney.org/professionals/KDOQI/guideline_diabetes/.and keep people off dialysis longer(289). However, nonrenal specialistsshould not delay educating their pa- (every 2–3 years) may be considered patients with high-risk PDR, clinicallytients about the progressive nature of following one or more normal eye ex- significant macular edema, and in somediabetic kidney disease; the renal pres- ams. Examinations will be required cases of severe NPDR. (A)ervation benefits of aggressive treat- more frequently if retinopathy is pro- ● The presence of retinopathy is not ament of blood pressure, blood glucose, gressing. (B) contraindication to aspirin therapy forand hyperlipidemia; and the potential ● High-quality fundus photographs can cardioprotection, as this therapy doesneed for renal replacement therapy. detect most clinically significant dia- not increase the risk of retinal hemor- betic retinopathy. Interpretation of the rhage. (A)C. Retinopathy screening and images should be performed by atreatment trained eye care provider. While retinal photography may serve as a screening Diabetic retinopathy is a highly specificRecommendations tool for retinopathy, it is not a substi- vascular complication of both type 1 and tute for a comprehensive eye exam, type 2 diabetes, with prevalence stronglyGeneral recommendations which should be performed at least ini- related to the duration of diabetes. Dia-● To reduce the risk or slow the progres- tially and at intervals thereafter as rec- betic retinopathy is the most frequent sion of retinopathy, optimize glycemic ommended by an eye care professional. cause of new cases of blindness among control. (A) (E) adults aged 20 –74 years. Glaucoma, cat-● To reduce the risk or slow the progres- ● Women with preexisting diabetes who aracts, and other disorders of the eye oc- sion of retinopathy, optimize blood are planning a pregnancy or who have cur earlier and more frequently in people pressure control. (A) become pregnant should have a com- with diabetes. prehensive eye examination and should In addition to duration of diabetes,Screening be counseled on the risk of develop- other factors that increase the risk of, or● Adults and children aged 10 years or ment and/or progression of diabetic ret- are associated with, retinopathy include older with type 1 diabetes should have inopathy. Eye examination should chronic hyperglycemia (290), the pres- an initial dilated and comprehensive occur in the first trimester with close ence of nephropathy (291), and hyper- eye examination by an ophthalmologist follow-up throughout pregnancy and tension (292). Intensive diabetes or optometrist within 5 years after the for 1 year postpartum. (B) management with the goal of achieving onset of diabetes. (B) near normoglycemia has been shown in● Patients with type 2 diabetes should Treatment large prospective randomized studies to have an initial dilated and comprehen- ● Promptly refer patients with any level of prevent and/or delay the onset and pro- sive eye examination by an ophthalmol- macular edema, severe NPDR, or any gression of diabetic retinopathy (47,55, ogist or optometrist shortly after the PDR to an ophthalmologist who is 56,64). Lowering blood pressure has diagnosis of diabetes. (B) knowledgeable and experienced in the been shown to decrease the progression● Subsequent examinations for type 1 management and treatment of diabetic of retinopathy (195). Several case series and type 2 diabetic patients should be retinopathy. (A) and a controlled prospective study sug- repeated annually by an ophthalmolo- ● Laser photocoagulation therapy is indi- gest that pregnancy in type 1 diabetic pa- gist or optometrist. Less frequent exams cated to reduce the risk of vision loss in tients may aggravate retinopathycare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S35
    • Standards of Medical Care(293,294); laser photocoagulation sur- after one or more normal eye exams, tient with diabetes is important for agery can minimize this risk (294). while examinations will be required more number of reasons: 1) nondiabetic neu- One of the main motivations for frequently if retinopathy is progressing ropathies may be present in patients withscreening for diabetic retinopathy is the (297). diabetes and may be treatable, 2) a num-established efficacy of laser photocoagu- The use of retinal photography with ber of treatment options exist for symp-lation surgery in preventing vision loss. remote reading by experts has great po- tomatic diabetic neuropathy, 3) up toTwo large trials, the Diabetic Retinopathy tential in areas where qualified eye care 50% of DPN may be asymptomatic andStudy (DRS) and the Early Treatment Di- professionals are not available, and may patients are at risk of insensate injury toabetic Retinopathy Study (ETDRS), pro- also enhance efficiency and reduce costs their feet, and 4) autonomic neuropathyvide the strongest support for the when the expertise of ophthalmologists and particularly cardiovascular auto-therapeutic benefits of photocoagulation can be utilized for more complex exami- nomic neuropathy is associated with sub-surgery. nations and for therapy (298). In-person stantial morbidity and even mortality. The DRS (295) showed that panreti- exams are still necessary when the photos Specific treatment for the underlyingnal photocoagulation surgery reduced the are unacceptable and for follow-up of ab- nerve damage is currently not available,risk of severe vision loss from PDR from normalities detected. Photos are not a other than improved glycemic control,15.9% in untreated eyes to 6.4% in substitute for a comprehensive eye exam, which may modestly slow progressiontreated eyes, with greatest risk-to-benefit which should be performed at least ini- (63) but not reverse neuronal loss. Effec-ratio in those with baseline disease (disc tially and at intervals thereafter as recom- tive symptomatic treatments are availableneovascularization or vitreous hemor- mended by an eye care professional. for some manifestations of DPN and au-rhage). Results of eye examinations should be tonomic neuropathy. The ETDRS (296) established the documented and transmitted to the refer-benefit of focal laser photocoagulation ring health care professional. For a de- Diagnosis of neuropathysurgery in eyes with macular edema, par- tailed review of the evidence and further Distal symmetric polyneuropathy. Pa-ticularly those with clinically significant discussion of diabetic retinopathy, see the tients with diabetes should be screenedmacular edema, with reduction of dou- ADA’s technical review and position state- annually for DPN using tests such as pin-bling of the visual angle (e.g., 20/50 to ment on this subject (297,300). prick sensation, vibration perception20/100) from 20% in untreated eyes to (using a 128-Hz tuning fork), 10-g mono-8% in treated eyes. The ETDRS also veri- D. Neuropathy screening and filament pressure sensation at the distalfied the benefits of panretinal photocoag- treatment (301) plantar aspect of both great toes andulation for high-risk PDR and in older- metatarsal joints, and assessment of ankleonset patients with severe NPDR or less- Recommendations reflexes. Combinations of more than onethan-high-risk PDR. ● All patients should be screened for dis- test have 87% sensitivity in detecting Laser photocoagulation surgery in tal symmetric polyneuropathy (DPN) at DPN. Loss of 10-g monofilament percep-both trials was beneficial in reducing the diagnosis and at least annually thereaf- tion and reduced vibration perceptionrisk of further vision loss, but generally ter, using simple clinical tests. (B) predict foot ulcers (301). Importantly, innot beneficial in reversing already dimin- ● Electrophysiological testing is rarely patients with neuropathy, particularlyished acuity. This preventive effect and needed, except in situations where the when severe, causes other than diabetesthe fact that patients with PDR or macular clinical features are atypical. (E) should always be considered, such asedema may be asymptomatic provide ● Screening for signs and symptoms of neurotoxic mediations, heavy metal poi-strong support for a screening program to autonomic neuropathy should be insti- soning, alcohol abuse, vitamin B12 defi-detect diabetic retinopathy. tuted at diagnosis of type 2 diabetes and ciency (especially in those taking As retinopathy is estimated to take at 5 years after the diagnosis of type 1 di- metformin for prolonged periods (302),least 5 years to develop after the onset of abetes. Special testing is rarely needed renal disease, chronic inflammatory de-hyperglycemia, patients with type 1 dia- and may not affect management or out- myelinating neuropathy, inherited neu-betes should have an initial dilated and comes. (E) ropathies, and vasculitis (303).comprehensive eye examination within 5 ● Medications for the relief of specific Diabetic autonomic neuropathy (304).years after the onset of diabetes. Patients symptoms related to DPN and auto- The symptoms and signs of autonomicwith type 2 diabetes, who generally have nomic neuropathy are recommended, dysfunction should be elicited carefullyhad years of undiagnosed diabetes and as they improve the quality of life of the during the history and physical examina-who have a significant risk of prevalent patient. (E) tion. Major clinical manifestations of dia-DR at time of diabetes diagnosis, should betic autonomic neuropathy includehave an initial dilated and comprehensive The diabetic neuropathies are heteroge- resting tachycardia, exercise intolerance,eye examination soon after diagnosis. Ex- neous with diverse clinical manifesta- orthostatic hypotension, constipation,aminations should be performed by an tions. They may be focal or diffuse. Most gastroparesis, erectile dysfunction, sudo-ophthalmologist or optometrist who is common among the neuropathies are motor dysfunction, impaired neurovas-knowledgeable and experienced in diag- chronic sensorimotor DPN and auto- cular function, and, potentially,nosing the presence of diabetic retinopa- nomic neuropathy. Although DPN is a di- autonomic failure in response to hypogly-thy and is aware of its management. agnosis of exclusion, complex cemia.Subsequent examinations for type 1 and investigations to exclude other conditions Cardiovascular autonomic neuropa-type 2 diabetic patients are generally re- are rarely needed. thy, a CVD risk factor (93), is the mostpeated annually. Less-frequent exams The early recognition and appropri- studied and clinically important form of(every 2–3 years) may be cost effective ate management of neuropathy in the pa- diabetic autonomic neuropathy. Cardio-S36 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementvascular autonomic neuropathy may be are described in the ADA statement on ● Visual impairmentindicated by resting tachycardia ( 100 neuropathy (301). As with DPN treat- ● Diabetic nephropathy (especially pa-bpm) or orthostasis (a fall in systolic ments, these interventions do not change tients on dialysis)blood pressure 20 mmHg upon stand- the underlying pathology and natural his- ● Poor glycemic controling without an appropriate heart rate re- tory of the disease process, but may have a ● Cigarette smokingsponse); it is also associated with positive impact on the quality of life of theincreased cardiac event rates. patient. Many studies have been published pro- Gastrointestinal neuropathies (e.g., posing a range of tests that might usefullyesophageal enteropathy, gastroparesis, E. Foot care identify patients at risk of foot ulceration,constipation, diarrhea, fecal inconti- creating confusion among practitioners asnence) are common, and any section of Recommendations to which screening tests should bethe gastrointestinal tract may be affected. ● For all patients with diabetes, perform adopted in clinical practice. An ADA taskGastroparesis should be suspected in in- an annual comprehensive foot exami- force was therefore assembled in 2008 todividuals with erratic glucose control or nation to identify risk factors predictive concisely summarize recent literature inwith upper gastrointestinal symptoms of ulcers and amputations. The foot ex- this area and then recommend whatwithout other identified cause. Evalua- amination should include inspection, should be included in the comprehensivetion of solid-phase gastric emptying using assessment of foot pulses, and testing foot exam for adult patients with diabetes.double-isotope scintigraphy may be done for loss of protective sensation (10-g Their recommendations are summarizedif symptoms are suggestive, but test re- monofilament plus testing any one of: below, but clinicians should refer to thesults often correlate poorly with symp- vibration using 128-Hz tuning fork, task force report (305) for further detailstoms. Constipation is the most common pinprick sensation, ankle reflexes, or and practical descriptions of how to per-lower-gastrointestinal symptom but can vibration perception threshold). (B) form components of the comprehensivealternate with episodes of diarrhea. ● Provide general foot self-care education foot examination. Diabetic autonomic neuropathy is to all patients with diabetes. (B) At least annually, all adults with dia-also associated with genitourinary tract ● A multidisciplinary approach is recom- betes should undergo a comprehensivedisturbances. In men, diabetic autonomic mended for individuals with foot ulcers foot examination to identify high riskneuropathy may cause erectile dysfunc- and high-risk feet, especially those with conditions. Clinicians should ask abouttion and/or retrograde ejaculation. Evalu- a history of prior ulcer or amputation. history of previous foot ulceration or am-ation of bladder dysfunction should be (B) putation, neuropathic or peripheral vas-performed for individuals with diabetes ● Refer patients who smoke, have loss of cular symptoms, impaired vision, tobaccowho have recurrent urinary tract infec- protective sensation and structural ab- use, and foot care practices. A general in-tions, pyelonephritis, incontinence, or a normalities, or have history of prior spection of skin integrity and musculo-palpable bladder. lower-extremity complications to foot skeletal deformities should be done in a care specialists for ongoing preventive well lit room. Vascular assessment wouldSymptomatic treatments care and life-long surveillance. (C) include inspection and assessment ofDPN. The first step in management of pa- ● Initial screening for peripheral arterial pedal pulses.tients with DPN should be to aim for sta- disease (PAD) should include a history The neurologic exam recommendedble and optimal glycemic control. for claudication and an assessment of is designed to identify loss of protectiveAlthough controlled trial evidence is lack- the pedal pulses. Consider obtaining an sensation (LOPS) rather than early neu-ing, several observational studies suggest ankle-brachial index (ABI), as many pa- ropathy. The clinical examination to iden-that neuropathic symptoms improve not tients with PAD are asymptomatic. (C) tify LOPS is simple and requires noonly with optimization of control, but ● Refer patients with significant claudica- expensive equipment. Five simple clinicalalso with the avoidance of extreme blood tion or a positive ABI for further vascu- tests (use of a 10-g monofilament, vibra-glucose fluctuations. Patients with painful lar assessment and consider exercise, tion testing using a 128-Hz tuning fork,DPN may benefit from pharmacological medications, and surgical options. (C) tests of pinprick sensation, ankle reflextreatment of their symptoms: many assessment, and testing vibration percep-agents have efficacy confirmed in pub- Amputation and foot ulceration, conse- tion threshold with a biothesiometer),lished randomized controlled trials, sev- quences of diabetic neuropathy and/or each with evidence from well-conductederal of which are Food and Drug PAD, are common and major causes of prospective clinical cohort studies, areAdministration (FDA)-approved for the morbidity and disability in people with considered useful in the diagnosis ofmanagement of painful DPN. diabetes. Early recognition and manage- LOPS in the diabetic foot. The task force ment of risk factors can prevent or delay agrees that any of the five tests listed couldTreatment of autonomic neuropathy adverse outcomes. be used by clinicians to identify LOPS,Gastroparesis symptoms may improve The risk of ulcers or amputations is although ideally two of these should bewith dietary changes and prokinetic increased in people who have the follow- regularly performed during the screeningagents such as metoclopramide or eryth- ing risk factors: exam—normally the 10-g monofilamentromycin. Treatments for erectile dysfunc- and one other test. One or more abnormaltion may include phosphodiesterase type ● Previous amputation tests would suggest LOPS, while at least5 inhibitors, intracorporeal or intraure- ● Past foot ulcer history two normal tests (and no abnormal test)thral prostaglandins, vacuum devices, or ● Peripheral neuropathy would rule out LOPS. The last test listed,penile prostheses. Interventions for other ● Foot deformity vibration assessment using a biothesiom-manifestations of autonomic neuropathy ● Peripheral vascular disease eter or similar instrument, is widely usedcare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S37
    • Standards of Medical Carein the U.S.; however, identification of the dated with commercial therapeutic foot- a. Glycemic controlpatient with LOPS can easily be carried wear may need custom-molded shoes.out without this or other expensive equip- Foot ulcers and wound care may re- Recommendationsment. quire care by a podiatrist, orthopedic or ● Consider age when setting glycemic Initial screening for PAD should in- vascular surgeon, or rehabilitation spe- goals in children and adolescents withclude a history for claudication and an cialist experienced in the management of type 1 diabetes. (E)assessment of the pedal pulses. A diagnos- individuals with diabetes.tic ABI should be performed in any pa- While current standards for diabetestient with symptoms of PAD. Due to the management reflect the need to maintainhigh estimated prevalence of PAD in pa- VII. DIABETES CARE IN glucose control as near to normal as safelytients with diabetes and the fact that many SPECIFIC POPULATIONS possible, special consideration should bepatients with PAD are asymptomatic, an given to the unique risks of hypoglycemiaADA consensus statement on PAD (306) A. Children and adolescents in young children. Glycemic goals maysuggested that a screening ABI be per- need to be modified to take into accountformed in patients over 50 years of age 1. Type 1 diabetes the fact that most children 6 or 7 yearsand be considered in patients under 50 Three-quarters of all cases of type 1 dia- of age have a form of “hypoglycemic un-years of age who have other PAD risk fac- betes are diagnosed in individuals 18 awareness,” including immaturity of andtors (e.g., smoking, hypertension, hyper- years of age. It is appropriate to consider a relative inability to recognize and re-lipidemia, or duration of diabetes 10 the unique aspects of care and manage- spond to hypoglycemic symptoms, plac-years). Refer patients with significant ment of children and adolescents with ing them at greater risk for severesymptoms or a positive ABI for further type 1 diabetes. Children with diabetes hypoglycemia and its sequelae. In addi-vascular assessment and consider exer- differ from adults in many respects, in- tion, and unlike the case in adults, youngcise, medications, and surgical options cluding changes in insulin sensitivity re- children under the age of 5 years may be(306). lated to sexual maturity and physical at risk for permanent cognitive impair- Patients with diabetes and high-risk growth, ability to provide self-care, super- ment after episodes of severe hypoglyce-foot conditions should be educated re- vision in child care and school, and mia (308 –310). Furthermore, findingsgarding their risk factors and appropriate unique neurological vulnerability to hy- from the DCCT demonstrated that near-management. Patients at risk should un- poglycemia and DKA. Attention to such normalization of blood glucose levels wasderstand the implications of the LOPS, issues as family dynamics, developmental more difficult to achieve in adolescentsthe importance of foot monitoring on a stages, and physiological differences re- than adults. Nevertheless, the increaseddaily basis, the proper care of the foot, lated to sexual maturity are all essential in frequency of use of basal-bolus regimensincluding nail and skin care, and the se- developing and implementing an optimal and insulin pumps in youth from infancylection of appropriate footwear. Patients diabetes regimen. Although recommen- through adolescence has been associatedwith LOPS should be educated on ways to dations for children and adolescents are with more children reaching ADA bloodsubstitute other sensory modalities (hand less likely to be based on clinical trial ev- glucose targets (311,312) in those fami-palpation, visual inspection) for surveil- idence, expert opinion and a review of lies in which both parents and the childlance of early foot problems. Patients’ un- available and relevant experimental data with diabetes participate jointly to per-derstanding of these issues and their are summarized in the ADA statement on form the required diabetes-related tasks.physical ability to conduct proper foot care of children and adolescents with type Furthermore, recent studies document-surveillance and care should be assessed. 1 diabetes (307). ing neurocognitive sequelae of hypergly-Patients with visual difficulties, physical Ideally, the care of a child or adoles- cemia in children provide anotherconstraints preventing movement, or cog- cent with type 1 diabetes should be pro- compelling motivation for achieving gly-nitive problems that impair their ability to vided by a multidisciplinary team of cemic targets (313,314).assess the condition of the foot and to in- specialists trained in the care of children In selecting glycemic goals, the bene-stitute appropriate responses will need with pediatric diabetes. At the very least, fits on long-term health outcomes ofother people, such as family members, to education of the child and family should achieving a lower A1C should be bal-assist in their care. be provided by health care providers anced against the risks of hypoglycemia People with neuropathy or evidence trained and experienced in childhood di- and the developmental burdens of inten-of increased plantar pressure (e.g., ery- abetes and sensitive to the challenges sive regimens in children and youth. Age-thema, warmth, callus, or measured pres- posed by diabetes in this age-group. At specific glycemic and A1C goals aresure) may be adequately managed with the time of initial diagnosis, it is essential presented in Table 16.well-fitted walking shoes or athletic shoes that diabetes education be provided in athat cushion the feet and redistribute timely fashion, with the expectation thatpressure. Callus can be debrided with a the balance between adult supervision b. Screening and management ofscalpel by a foot care specialist or other and self-care should be defined by, and chronic complications in childrenhealth professional with experience and will evolve according to, physical, psy- and adolescents with type 1 diabetestraining in foot care. People with bony chological, and emotional maturity. MNTdeformities (e.g., hammertoes, promi- and psychological support should be pro- i. Nephropathynent metatarsal heads, bunions) may vided at diagnosis, and regularly thereaf-need extra-wide or -depth shoes. People ter, by individuals experienced with the Recommendationswith extreme bony deformities (e.g., nutritional and behavioral needs of the ● Annual screening for microalbumin-Charcot foot) who cannot be accommo- growing child and family. uria, with a random spot urine sampleS38 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementTable 16—Plasma blood glucose and A1C goals for type 1 diabetes by age-group Plasma blood glucose goal range (mg/dl) Before meals Bedtime/overnight A1C (%) RationaleToddlers and preschoolers 100–180 110–200 8.5 • Vulnerability to hypoglycemia (0–6 years) • Insulin sensitivity • Unpredictability in dietary intake and physical activity • A lower goal ( 8.0%) is reasonable if it can be achieved without excessive hypoglycemiaSchool age (6–12 years) 90–180 100–180 8 • Vulnerability to hypoglycemia • A lower goal ( 7.5%) is reasonable if it can be achieved without excessive hypoglycemiaAdolescents and young adults 90–130 90–150 7.5 • A lower goal ( 7.0%) is reasonable if (13–19 years) 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 modified 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. for albumin-to-creatinine (ACR) ra- percentile for age, sex, and height or iii. Dyslipidemia tio, should be considered once the consistently greater than 130/80 child is 10 years of age and has had mmHg, if 95% exceeds that value) Recommendations diabetes for 5 years. (E) should be initiated as soon as the di-● Confirmed, persistently elevated ACR agnosis is confirmed. (E) on two additional urine specimens ● ACE inhibitors should be considered Screening from different days should be treated ● If there is a family history of hypercho- for the initial treatment of hyperten- with an ACE inhibitor, titrated to nor- sion, following appropriate reproduc- lesterolemia (total cholesterol 240 malization of albumin excretion if tive counseling due to its potential mg/dl) or a cardiovascular event before possible. (E) teratogenic effects. (E) age 55 years, or if family history is un- ● known, then a fasting lipid profile The goal of treatment is a blood pres-ii. Hypertension should be performed on children 2 sure consistently 130/80 or below the years of age soon after diagnosis (after 90th percentile for age, sex, and height,Recommendations glucose control has been established).● Treatment of high-normal blood whichever is lower. (E) If family history is not of concern, then pressure (systolic or diastolic blood the first lipid screening should be con- pressure consistently above the 90th sidered at puberty ( 10 years). All chil- It is important that blood pressure mea- percentile for age, sex, and height) dren diagnosed with diabetes at or after surements are determined correctly, us- should include dietary intervention puberty should have a fasting lipid pro- ing the appropriate size cuff, and with and exercise aimed at weight control file performed soon after diagnosis and increased physical activity, if ap- the child seated and relaxed. Hyperten- (after glucose control has been estab- propriate. If target blood pressure is sion should be confirmed on at least lished). (E) not reached with 3– 6 months of life- three separate days. Normal blood pres- ● For both age-groups, if lipids are abnor- style intervention, pharmacologic sure levels for age, sex, and height and mal, annual monitoring is recom- treatment should be considered. (E) appropriate methods for determina- mended. If LDL cholesterol values are● Pharmacologic treatment of hyper- tions are available online at www.nhlbi. within the accepted risk levels ( 100 tension (systolic or diastolic blood nih.gov/health/prof/heart/hbp/hbp_ mg/dl [2.6 mmol/l]), a lipid profile pressure consistently above the 95th ped.pdf. should be repeated every 5 years. (E)care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S39
    • Standards of Medical CareTreatment Although retinopathy most commonly long-term benefit of gluten-free diets in● Initial therapy should consist of optimi- occurs after the onset of puberty and after this population. zation of glucose control and MNT us- 5–10 years of diabetes duration, it has ing a Step 2 AHA diet aimed at a been reported in prepubertal children vi. Hypothyroidism decrease in the amount of saturated fat and with diabetes duration of only 1–2 in the diet. (E) years. Referrals should be made to eye● After the age of 10 years, the addition of care professionals with expertise in dia- Recommendations a statin in patients who, after MNT and betic retinopathy, an understanding of ● Children with type 1 diabetes should be lifestyle changes, have LDL cholesterol the risk for retinopathy in the pediatric screened for thyroid peroxidase and 160 mg/dl (4.1 mmol/l), or LDL cho- population, and experience in counsel- thyroglobulin antibodies at diagnosis. lesterol 130 mg/dl (3.4 mmol/l) and ing the pediatric patient and family on (E) one or more CVD risk factors, is reason- the importance of early prevention/ ● TSH concentrations should be mea- able. (E) intervention. sured after metabolic control has been● The goal of therapy is an LDL choles- established. If normal, they should be terol value 100 mg/dl (2.6 mmol/l). v. Celiac disease re-checked every 1–2 years, or if the (E) patient develops symptoms of thyroid Recommendations dysfunction, thyromegaly, or an abnor-People diagnosed with type 1 diabetes in ● Children with type 1 diabetes should mal growth rate. (E)childhood have a high risk of early sub- be screened for celiac disease by mea-clinical (315–317) and clinical (318) suring tissue transglutaminase or Auto-immune thyroid disease is the mostCVD. Although intervention data are anti-endomysial antibodies, with common autoimmune disorder associ-lacking, the AHA categorizes children documentation of normal total serum ated with diabetes, occurring in 17–30%with type 1 diabetes in the highest tier for IgA levels, soon after the diagnosis of of patients with type 1 diabetes (328). Thecardiovascular risk and recommends diabetes. (E) presence of thyroid auto-antibodies isboth lifestyle and pharmacologic treat- ● Testing should be repeated in children predictive of thyroid dysfunction, gener-ment for those with elevated LDL choles- with growth failure, failure to gain ally hypothyroidism but less commonlyterol levels (319,320). Initial therapy weight, weight loss, diarrhea, flatu- hyperthyroidism (329). Subclinical hy-should be with a Step 2 AHA diet, which lence, abdominal pain, or signs of mal- pothyroidism may be associated withrestricts saturated fat to 7% of total calo- absorption, or in children with increased risk of symptomatic hypoglyce-ries and restricts dietary cholesterol to frequent unexplained hypoglycemia or mia (330) and with reduced linear growth200 mg/day. Data from randomized clin- deterioration in glycemic control. (E) (331). Hyperthyroidism alters glucoseical trials in children as young as 7 ● Children with positive antibodies metabolism, potentially resulting in dete-months of age indicate that this diet is safe should be referred to a gastroenterolo- rioration of metabolic control.and does not interfere with normal gist for evaluation with endoscopy andgrowth and development (321,322). biopsy. (E) ● Children with biopsy-confirmed celiac c. Self-management Neither long-term safety nor cardio- No matter how sound the medical regi-vascular outcome efficacy of statin ther- disease should be placed on a gluten- free diet and have consultation with a men, it can only be as good as the ability ofapy has been established for children. the family and/or individual to implementHowever, recent studies have shown dietitian experienced in managing both diabetes and celiac disease. (E) it. Family involvement in diabetes re-short-term safety equivalent to that seen mains an important component of opti-in adults, and efficacy in lowering LDL mal diabetes management throughoutcholesterol levels, improving endothelial Celiac disease is an immune-mediated disorder that occurs with increased fre- childhood and into adolescence. Healthfunction, and causing regression of ca- care providers who care for children androtid intimal thickening (323–325). No quency in patients with type 1 diabetes (1–16% of individuals compared with adolescents, therefore, must be capable ofstatin is approved for use under the age of evaluating the behavioral, emotional, and10 years, and statin treatment should gen- 0.3–1% in the general population) (326,327). Symptoms of celiac disease in- psychosocial factors that interfere witherally not be used in children with type 1 implementation and then must work withdiabetes prior to this age. clude diarrhea, weight loss or poor weight gain, growth failure, abdominal pain, the individual and family to resolve prob- chronic fatigue, malnutrition due to mal- lems that occur and/or to modify goals asiv. Retinopathy absorption, other gastrointestinal prob- appropriate. lems, and unexplained hypoglycemia orRecommendations erratic blood glucose concentrations. d. School and day care● The first ophthalmologic examination The advent of routine periodic Because a sizable portion of a child’s day is should be obtained once the child is 10 screening has led to the diagnosis of celiac spent in school, close communication years of age and has had diabetes for disease in asymptomatic children. While with and cooperation of school or day 3–5 years. (E) several studies have documented short- care personnel is essential for optimal di-● After the initial examination, annual term benefits of gluten restriction on abetes management, safety, and maximal routine follow-up is generally recom- growth and bone mineral density in academic opportunities. See the ADA po- mended. Less frequent examinations asymptomatic children diagnosed with sition statement on Diabetes Care in the may be acceptable on the advice of an celiac disease by routine screening, there School and Day Care Setting (332) for fur- eye care professional. (E) is little literature available regarding the ther discussion.S40 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statemente. Transition from pediatric to adult 3. Monogenic diabetes syndromes counsel women using such medica-care Monogenic forms of diabetes (neonatal tions accordingly. (E)As they approach the young adult years, diabetes or maturity-onset diabetes of theolder adolescents are at increasing physi- young) represent a small fraction of chil- Major congenital malformations remaincal, behavioral, and other risks (333,334). dren with diabetes ( 5%), but the ready the leading cause of mortality and seriousAs they leave both their home and their availability of commercial genetic testing morbidity in infants of mothers with typepediatric diabetes care providers, these is now enabling a true genetic diagnosis 1 and type 2 diabetes. Observational stud-older teens may become disengaged from with increasing frequency. It is important ies indicate that the risk of malformationsthe health care system, leading to lapses in to correctly diagnose one of the mono- increases continuously with increasingmedical care and deterioration in glyce- genic forms of diabetes, as these children maternal glycemia during the first 6 – 8mic control (335). Though scientific evi- may be incorrectly diagnosed with type 1 weeks of gestation, as defined by first-dence is limited to date, it is clear that or type 2 diabetes, leading to nonoptimal trimester A1C concentrations. There is noearly and ongoing attention be given to treatment regimens and delays in diag- threshold for A1C values below whichcomprehensive and coordinated planning nosing other family members. risk disappears entirely. However, mal-for seamless transition of all youth from The diagnosis of monogenic diabetes formation rates above the 1–2% back-pediatric to adult health care (336,337). should be considered in the following set- ground rate of nondiabetic pregnanciesThe National Diabetes Education Pro- tings: diabetes diagnosed within the first 6 appear to be limited to pregnancies ingram (NDEP) has materials available to months of life; in children with strong which first-trimester A1C concentrationsfacilitate this transition process (http:// family history of diabetes but without typ- are 1% above the normal range for andep.nih.gov/transitions/). ical features of type 2 diabetes (nonobese, nondiabetic pregnant woman. low-risk ethnic group); in children with Preconception care of diabetes ap- mild fasting hyperglycemia (100 –150 pears to reduce the risk of congenital mal-2. Type 2 diabetes mg/dl [5.5– 8.5 mmol]), especially if formations. Five nonrandomized studiesThe incidence of type 2 diabetes in ado- young and nonobese; and in children compared rates of major malformations inlescents is increasing, especially in ethnic with diabetes but with negative auto- infants between women who participatedminority populations (21). Distinction antibodies without signs of obesity or in- in preconception diabetes care programsbetween type 1 and type 2 diabetes in sulin resistance. A recent international and women who initiated intensive diabe-children can be difficult, since the preva- consensus document discusses in further tes management after they were already detail the diagnosis and management of pregnant. The preconception care pro-lence of overweight in children continues children with monogenic forms of diabe- grams were multidisciplinary and de-to rise and since autoantigens and ketosis tes (339). signed to train patients in diabetes self-may be present in a substantial number of management with diet, intensified insulinpatients with features of type 2 diabetes therapy, and SMBG. Goals were set to(including obesity and acanthosis nigri- B. Preconception care achieve normal blood glucose concentra-cans). Such a distinction at the time of tions, and 80% of subjects achieveddiagnosis is critical since treatment regi- Recommendations normal A1C concentrations before theymens, educational approaches, and di- ● A1C levels should be as close to normal became pregnant. In all five studies, theetary counsel will differ markedly as possible ( 7%) in an individual pa- incidence of major congenital malforma-between the two diagnoses. tient before conception is attempted. tions in women who participated in pre- Type 2 diabetes has a significant preva- (B) conception care (range 1.0 –1.7% oflence of comorbidities already present at the ● Starting at puberty, preconception infants) was much lower than the inci-time of diagnosis (338). It is recommended counseling should be incorporated in dence in women who did not participatethat blood pressure measurement, a fasting the routine diabetes clinic visit for all (range 1.4 –10.9% of infants) (78). Onelipid profile, microalbuminuria assessment, women of child-bearing potential. (C) limitation of these studies is that partici-and dilated eye examination be performed ● Women with diabetes who are contem- pation in preconception care was self-at the time of diagnosis. Thereafter, screen- plating pregnancy should be evaluated selected rather than randomized. Thus, iting guidelines and treatment recommen- and, if indicated, treated for diabetic is impossible to be certain that the lowerdations for hypertension, dyslipidemia, retinopathy, nephropathy, neuropathy, malformation rates resulted fully frommicroalbuminuria, and retinopathy in and CVD. (E) improved diabetes care. Nonetheless, theyouth with type 2 diabetes are similar to ● Medications used by such women evidence supports the concept that mal-those for youth with type 1 diabetes. Ad- should be evaluated prior to concep- formations can be reduced or preventedditional problems that may need to be ad- tion, since drugs commonly used to by careful management of diabetes beforedressed include polycystic ovary disease treat diabetes and its complications pregnancy.and the various comorbidities associated may be contraindicated or not recom- Planned pregnancies greatly facili-with pediatric obesity such as sleep ap- mended in pregnancy, including st- tate preconception diabetes care. Un-nea, hepatic steatosis, orthopedic compli- atins, ACE inhibitors, ARBs, and most fortunately, nearly two-thirds ofcations, and psychosocial concerns. The noninsulin therapies. (E) pregnancies in women with diabetes areADA consensus statement on this subject ● Since many pregnancies are un- unplanned, leading to a persistent ex-(23) provides guidance on the preven- planned, consider the potential risks cess of malformations in infants of dia-tion, screening, and treatment of type 2 and benefits of medications that are betic mothers. To minimize thediabetes and its comorbidities in young contraindicated in pregnancy in all occurrence of these devastating malfor-people. women of childbearing potential, and mations, standard care for all womencare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S41
    • Standards of Medical Carewith diabetes who have child-bearing C. Older adults ing chronic conditions, substantial diabe-potential, beginning at the onset of pu- tes-related comorbidity, or limitedberty or at diagnosis, should include 1) Recommendations physical or cognitive functioning. Othereducation about the risk of malforma- ● Older adults who are functional, cogni- older individuals with diabetes have littletions associated with unplanned preg- tively intact, and have significant life comorbidity and are active. Life expectan-nancies and poor metabolic control; expectancy should receive diabetes care cies are highly variable for this popula-and 2) use of effective contraception at using goals developed for younger tion, but often longer than cliniciansall times, unless the patient has good adults. (E) realize. Providers caring for older adultsmetabolic control and is actively trying ● Glycemic goals for older adults not with diabetes must take this heterogeneityto conceive. meeting the above criteria may be re- into consideration when setting and pri- Women contemplating pregnancy laxed using individual criteria, but hy- oritizing treatment goals.need to be seen frequently by a multi- perglycemia leading to symptoms or There are few long-term studies indisciplinary team experienced in the risk of acute hyperglycemic complica- older adults demonstrating the benefits ofmanagement of diabetes before and tions should be avoided in all patients. intensive glycemic, blood pressure, andduring pregnancy. The goals of precon- (E) lipid control. Patients who can be expectedception care are to 1) involve and em- ● Other cardiovascular risk factors to live long enough to reap the benefits ofpower the patient in the management of should be treated in older adults with long-term intensive diabetes managementher diabetes, 2) achieve the lowest A1C consideration of the time frame of ben- and who are active, have good cognitivetest results possible without excessive efit and the individual patient. Treat- function, and are willing should be pro-hypoglycemia, 3) assure effective con- ment of hypertension is indicated in vided with the needed education and skillstraception until stable and acceptable virtually all older adults, and lipid and to do so and be treated using the goals forglycemia is achieved, and 4) identify, aspirin therapy may benefit those with younger adults with diabetes.evaluate, and treat long-term diabetes life expectancy at least equal to the time For patients with advanced diabetescomplications such as retinopathy, ne- frame of primary or secondary preven- complications, life-limiting comorbid ill-phropathy, neuropathy, hypertension, tion trials. (E) ness, or substantial cognitive or func-and CHD (78). ● Screening for diabetes complications tional impairment, it is reasonable to set Among the drugs commonly used in should be individualized in older less-intensive glycemic target goals. Thesethe treatment of patients with diabetes, adults, but particular attention should patients are less likely to benefit from re-a number may be relatively or abso- be paid to complications that would ducing the risk of microvascular compli-lutely contraindicated during preg- lead to functional impairment. (E) cations and more likely to suffer seriousnancy. Statins are category X adverse effects from hypoglycemia.(contraindicated for use in pregnancy) Diabetes is an important health condition However, patients with poorly controlledand should be discontinued before con- for the aging population; at least 20% of diabetes may be subject to acute compli-ception, as should ACE inhibitors patients over the age of 65 years have di- cations of diabetes, including dehydra-(340). ARBs are category C (risk cannot abetes, and this number can be expected tion, poor wound healing, andbe ruled out) in the first trimester but to grow rapidly in the coming decades. hyperglycemic hyperosmolar coma. Gly-category D (positive evidence of risk) in Older individuals with diabetes have cemic goals at a minimum should avoidlater pregnancy and should generally be higher rates of premature death, func- these consequences.discontinued before pregnancy. Since tional disability, and coexisting illnesses Although control of hyperglycemiamany pregnancies are unplanned, such as hypertension, CHD, and stroke may be important in older individualshealth care professionals caring for any than those without diabetes. Older adults with diabetes, greater reductions in mor-woman of childbearing potential should with diabetes are also at greater risk than bidity and mortality may result from con-consider the potential risks and benefits other older adults for several common ge- trol of other cardiovascular risk factorsof medications that are contraindicated riatric syndromes, such as polypharmacy, rather than from tight glycemic controlin pregnancy. Women using medica- depression, cognitive impairment, uri- alone. There is strong evidence from clin-tions such as statins or ACE inhibitors nary incontinence, injurious falls, and ical trials of the value of treating hyper-need ongoing family planning counsel- persistent pain. tension in the elderly (343,344). There ising. Among the oral antidiabetic agents, The American Geriatric Society’s less evidence for lipid-lowering and aspi-metformin and acarbose are classified as guidelines for improving the care of the rin therapy, although the benefits of thesecategory B (no evidence of risk in hu- older person with diabetes (342) have in- interventions for primary and secondarymans) and all others as category C. Po- fluenced the following discussion and prevention are likely to apply to oldertential risks and benefits of oral recommendations. The care of older adults whose life expectancies equal orantidiabetic agents in the preconception adults with diabetes is complicated by exceed the time frames seen in clinicalperiod must be carefully weighed, rec- their clinical and functional heterogene- trials.ognizing that data are insufficient to es- ity. Some older individuals developed di- Special care is required in prescribingtablish the safety of these agents in abetes years earlier and may have and monitoring pharmacologic therapy inpregnancy. significant complications; others who are older adults. Metformin is often contrain- For further discussion of preconcep- newly diagnosed may have had years of dicated because of renal insufficiency ortion care, see the ADA’s consensus state- undiagnosed diabetes with resultant com- significant heart failure. TZDs can causement on preexisting diabetes and plications or may have few complications fluid retention, which may exacerbate orpregnancy (78) and the position state- from the disease. Some older adults with lead to heart failure. They are contraindi-ment (341) on this subject. diabetes are frail and have other underly- cated in patients with CHF (New YorkS42 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position StatementHeart Association class III and class IV) clearly identified in the medical record. same glycemic goals as patients withand if used at all should be used very cau- (E) known diabetes. (E)tiously in those with, or at risk for, milder ● All patients with diabetes should have ● A hypoglycemia management protocoldegrees of CHF. Sulfonylureas, other in- an order for blood glucose monitoring, should be adopted and implementedsulin secretagogues, and insulin can cause with results available to all members of by each hospital or hospital system. Ahypoglycemia. Insulin use requires that the health care team. (E) plan for treating hypoglycemia shouldpatients or caregivers have good visual ● Goals for blood glucose levels: be established for each patient. Epi-and motor skills and cognitive ability. ● Critically ill patients: Insulin therapy sodes of hypoglycemia in the hospitalDrugs should be started at the lowest dose should be initiated for treatment of should be documented in the medialand titrated up gradually until targets are persistent hyperglycemia starting at a record and tracked. (E)reached or side effects develop. threshold of no greater than 180 ● All patients with diabetes admitted to Screening for diabetes complications mg/dl (10 mmol/l). Once insulin the hospital should have an A1C ob-in older adults also should be individual- therapy is started, a glucose range of tained if the result of testing in the pre-ized. Particular attention should be paid 140 –180 mg/dl (7.8 –10 mmol/l) is vious 2–3 months is not available. (E)to complications that can develop over ● Patients with hyperglycemia in the hos- recommended for the majority ofshort periods of time and/or that would critically ill patients. (A) pital who do not have a diagnosis ofsignificantly impair functional status, ● More stringent goals, such as 110 – diabetes should have appropriate planssuch as visual and lower-extremity com- 140 mg/dl (6.1–7.8 mmol/l) may be for follow-up testing and care docu-plications. appropriate for selected patients, as mented at discharge. (E) long as this can be achieved withoutD. Cystic fibrosis–related diabetes significant hypoglycemia. (C) Hyperglycemia in the hospital is exten-Cystic fibrosis–related diabetes (CFRD) is ● Critically ill patients require an intra- sively reviewed in an ADA technical re-the most common comorbidity in persons venous insulin protocol that has view (345). A recent updated consensuswith CF, occurring in about 20% of ado- demonstrated efficacy and safety in statement by the American Association oflescents and 40 –50% of adults. The addi- achieving the desired glucose range Clinical Endocrinologists (AACE) and thetional diagnosis of diabetes in this without increasing risk for severe hy- ADA (346) forms the basis for the discus-population is associated with worse nutri- poglycemia. (E) sion and guidelines in this section.tional status, more-severe inflammatory ● Non– critically ill patients: There is The literature on hospitalized pa-lung disease, and greater mortality from tients with hyperglycemia typically de- no clear evidence for specific bloodrespiratory failure. For reasons that are scribes three categories: glucose goals. If treated with insulin,not well understood, women with CFRD the premeal blood glucose targetare particularly vulnerable to excess mor- 1. Medical history of diabetes: diabetes should generally be 140 mg/dl (7.8bidity and mortality. Insulin insufficiency has been previously diagnosed and ac- mmol/l) with random blood glucoserelated to partial fibrotic destruction of knowledged by the patient’s treatingthe islet mass is the primary defect in 180 mg/dl (10.0 mmol/l), provided physician.CFRD. Genetically determined function these targets can be safely achieved. 2. Unrecognized diabetes: hyperglycemiaof the remaining -cells and insulin resis- More stringent targets may be appro- (fasting blood glucose 126 mg/dl ortance associated with infection and in- priate in stable patients with previous random blood glucose 200 mg/dl)flammation may also play a role. tight glycemic control. Less stringent occurring during hospitalization andEncouraging new data suggest that early targets may be appropriate in those confirmed as diabetes after hospitaliza-detection and aggressive insulin therapy with severe comorbidites. (E) tion by standard diagnostic criteria but ● Scheduled subcutaneous insulin withhave narrowed the gap in mortality be- unrecognized as diabetes by the treat-tween CF patients with and without dia- basal, nutritional, and correction com- ing physician during hospitalization.betes, and have eliminated the sex ponents is the preferred method for 3. Hospital-related hyperglycemia: hy-difference in mortality. achieving and maintaining glucose perglycemia (fasting blood glucose A consensus conference on CFRD control in noncritically ill patients. (C) 126 mg/dl or random blood glucosewas co-sponsored in 2009 by the Ameri- Using correction dose or “supplemen- 200 mg/dl) occurring during thecan Diabetes Association, the Cystic Fi- tal” insulin to correct premeal hyper- hospitalization that reverts to normalbrosis Foundation, and the Pediatric glycemia in addition to scheduled after hospital discharge.Endocrine Society. Recommendations for prandial and basal insulin is recom-the clinical management of CFRD can be mended. (E) The management of hyperglycemia in thefound in an ADA position statement ● Glucose monitoring should be initiated hospital has often been considered sec-(344a). in any patient not known to be diabetic ondary in importance to the condition who receives therapy associated with that prompted admission (345). How-VIII. DIABETES CARE IN SPECIFIC high risk for hyperglycemia, including ever, a body of literature now supportsSETTINGS high-dose glucocorticoid therapy, initi- targeted glucose control in the hospital ation of enteral or parenteral nutrition, setting for potential improved clinicalA. Diabetes care in the hospital or other medications such as octreotide outcomes. Hyperglycemia in the hospital or immunosuppressive medications. may result from stress, decompensationRecommendations (B) If hyperglycemia is documented of type 1 or type 2 or other forms of dia-● All patients with diabetes admitted to and persistent, treatment is necessary. betes, and/or may be iatrogenic due to the hospital should have their diabetes Such patients should be treated to the withholding of anti-hyperglycemic medi-care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S43
    • Standards of Medical Carecations or administration of hyperglyce- trolled group is unknown. The results of level 70 mg/dl (3.9 mmol/l). This is themia-provoking agents such as this study lie in stark contrast to a famous standard definition in outpatients andglucocorticoids or vasopressors. 2001 single-center study that reported a correlates with the initial threshold for the People with diabetes are more likely 42% relative reduction in intensive-care release of counterregulatory hormones.to be hospitalized and to have longer unit (ICU) mortality in critically ill surgi- Severe hypoglycemia in hospitalized pa-lengths of stay than those without diabe- cal patients treated to a target blood glu- tients has been defined by many as 40tes. A recent survey estimated that 22% of cose of 80 –110 mg/dl (350). Importantly, mg/dl (2.2 mmol/l), although this is lowerall hospital inpatient days were incurred the control group in NICE-SUGAR had than the 50 mg/dl (2.8 mmol/l) level atby people with diabetes and that hospital reasonably good blood glucose manage- which cognitive impairment begins ininpatient care accounted for half of the ment maintained at a mean glucose of 144 normal individuals (359). As with hyper-$174 billion total U.S. medical expendi- mg/dl, only 29 mg/dl above the inten- glycemia, hypoglycemia among inpa-tures for this disease (347). This is due, in sively managed patients. Accordingly, tients is also associated with adversepart, to the continued expansion of the this study’s findings do not disprove the short- and long-term outcomes. Early rec-worldwide epidemic of type 2 diabetes. notion that glycemic control in the ICU is ognition and treatment of mild to moder-While the costs of illness-related stress important. However, they do strongly ate hypoglycemia (40 and 69 mg/dl) (2.2hyperglycemia are not known, they are suggest that it is not necessary to target and 3.8 mmol/l) can prevent deteriora-likely to be significant given the poor blood glucose values 140 mg/dl, and tion to a more severe episode with poten-prognosis of such patients (348 –351). that a highly stringent target of 110 tial adverse sequelae (346). There is substantial observational ev- mg/dl may actually be dangerous.idence linking hyperglycemia in hospital- In a recent meta-analysis of 26 trials Critically ill patientsized patients (with or without diabetes) to (N 13,567), which included the NICE- Based on the weight of the available evi-poor outcomes. Cohort studies as well as SUGAR data, the pooled relative risk (RR) dence, for the majority of critically ill pa-a few early randomized controlled trials of death with intensive insulin therapy tients in the ICU setting, insulin infusion(RCTs) suggested that intensive treatment was 0.93 as compared with conventional should be used to control hyperglycemia,of hyperglycemia improved hospital out- therapy (95% CI 0.83–1.04) (357). Ap- with a starting threshold of no higher thancomes (345,350,351). In general, these proximately half of these trials reported 180 mg/dl (10.0 mmol/l). Once intrave-studies were heterogeneous in terms of hypoglycemia, with a pooled RR of inten- nous insulin is started, the glucose levelpatient population, blood glucose targets sive therapy of 6.0 (95% CI 4.5– 8.0). The should be maintained between 140 andand insulin protocols, provision of nutri- specific ICU setting influenced the find- 180 mg/dl (7.8 and 10.0 mmol/l). Greatertional support, and the proportion of pa- ings, with patients in surgical ICUs ap- benefit maybe realized at the lower end oftients receiving insulin, which limits the pearing to benefit from intensive insulin this range. Although strong evidence isability to make meaningful comparisons therapy (RR 0.63 [95% CI 0.44 – 0.91]), lacking, somewhat lower glucose targetsamong them. Recent trials in critically ill while those in other critical care settings may be appropriate in selected patients.patients have failed to show a significant did not (medical ICU, RR 1.0 [95% CI However, targets less than 110 mg/dl (6.1improvement in mortality with intensive 0.78 –1.28]; “mixed” ICU, RR 0.99 [95% mmol/l) are not recommended. Use of in-glycemic control (352,353) or have even CI 0.86 –1.12]). It was concluded that sulin infusion protocols with demon-shown increased mortality risk (354). overall, intensive insulin therapy in- strated safety and efficacy, resulting inMoreover, these recent RCTs have high- creased the risk of hypoglycemia but pro- low rates of hypoglycemia, are highly rec-lighted the risk of severe hypoglycemia vided no overall benefit on mortality in ommended (346).resulting from such efforts (352–357). the critically ill, although a possible mor- The largest study to date, NICE- tality benefit to patients admitted to the Noncritically ill patientsSUGAR, a multicenter, multinational surgical ICU (RR 0.63 [95% CI 0.44 – With no prospective RCT data to informRCT, compared the effect of intensive gly- 0.91]) was suggested. specific glycemic targets in noncriticallycemic control (target 81–108 mg/dl, ill patients, recommendations are basedmean blood glucose attained 115 mg/dl) 1. Glycemic targets in hospitalized on clinical experience and judgment. Forto standard glycemic control (target 144 – patients the majority of noncritically ill patients180 mg/dl, mean blood glucose attained treated with insulin, premeal glucose tar-144 mg/dl) on outcomes among 6,104 Definition of glucose abnormalities gets should generally be 140 mg/dl (7.8critically ill participants, the majority of in the hospital setting mmol/l) with random blood glucose lev-whom ( 95%) required mechanical ven- Hyperglycemia has been defined as any els 180 mg/dl (10.0 mmol/l), as long astilation (354). Ninety-day mortality was blood glucose level 140 mg/dl (7.8 these targets can be safely achieved. Tosignificantly higher in the intensive versus mmol/l). Levels that are significantly and avoid hypoglycemia, considerationthe conventional group (78 more deaths; persistently above this may require treat- should be given to reassessing the insulin27.5% vs. 24.9%, P 0.02) in both sur- ment in hospitalized patients. In patients regimen if blood glucose levels fall belowgical and medical patients. Mortality from without a previous diagnosis of diabetes, 100 mg/dl (5.6 mmol/l). Modification ofcardiovascular causes was more common elevated blood glucose may be due to the regimen is required when blood glu-in the intensive group (76 more deaths; “stress hyperglycemia,” a condition that cose values are 70 mg/dl (3.9 mmol/l),41.6% vs. 35.8%; P 0.02). Severe hy- can be established by a review of prior unless the event is easily explained bypoglycemia was also more common in the records or measurement of an A1C. A1C other factors (such as a missed meal, etc.)intensively treated group (6.8% vs. 0.5%; values 6.5% suggest that diabetes pre- Occasional patients with a prior his-P 0.001). The precise reason for the ceded hospitalization (358). Hypoglyce- tory of successful tight glycemic control inincreased mortality in the tightly con- mia has been defined as any blood glucose the outpatient setting who are clinicallyS44 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementstable may be maintained with a glucose quired with metformin, due to the possi- hospital outcomes, hospitals will needrange below the above cut points. Con- bility that a contraindication may develop multidisciplinary support to develop in-versely, higher glucose ranges may be ac- during the hospitalization, such as renal sulin management protocols that effec-ceptable in terminally ill patients or in insufficiency, unstable hemodynamic sta- tively and safely enable achievement ofpatients with severe comorbidities, as tus, or need for an imaging study that re- glycemic targets (366).well as in those in patient-care settings quires a radio-contrast dye.where frequent glucose monitoring or 5. Self-management in the hospitalclose nursing supervision is not feasible. 3. Preventing hypoglycemia Self-management of diabetes in the hos- Clinical judgment, combined with Hypoglycemia, especially in insulin- pital may be appropriate for competentongoing assessment of the patient’s clini- treated patients, is the leading limiting adult patients who: have a stable level ofcal status, including changes in the trajec- factor in the glycemic management of consciousness, have reasonably stabletory of glucose measures, the severity of type 1 and type 2 diabetes (173). In the daily insulin requirements, successfullyillness, nutritional status, or concurrent hospital, multiple additional risk factors conduct self-management of diabetes atuse of medications that might affect glu- for hypoglycemia are present. Patients home, have physical skills needed to suc-cose levels (e.g., steroids, octreotide) with or without diabetes may experience cessfully self-administer insulin and per-must be incorporated into the day-to-day hypoglycemia in the hospital in associa- form SMBG, have adequate oral intake,decisions regarding insulin dosing (346). tion with altered nutritional state, heart and are proficient in carbohydrate count- failure, renal or liver disease, malignancy, ing, use of multiple daily insulin injec-2. Anti-hyperglycemic agents in infection, or sepsis. Additional triggering tions or insulin pump therapy, and sick-hospitalized patients events leading to iatrogenic hypoglycemia day management. The patient andIn the hospital setting, insulin therapy is include sudden reduction of corticoste- physician, in consultation with nursingthe preferred method of glycemic control roid dose, altered ability of the patient to staff, must agree that patient self-in majority of clinical situations (346). In report symptoms, reduction of oral in- management is appropriate under thethe ICU, intravenous infusion is the pre- take, emesis, new NPO status, inappro- conditions of hospitalization.ferred route of insulin administration. priate timing of short- or rapid-acting Patients who use CSII pump therapyWhen the patient is transitioned off intra- insulin in relation to meals, reduction of in the outpatient setting can be candidatesvenous insulin to subcutaneous therapy, rate of administration of intravenous dex- for diabetes self-management in the hos-precautions should be taken to prevent trose, and unexpected interruption of en- pital, provided that they have the mentalhyperglycemia escape (360,361). Outside teral feedings or parenteral nutrition. and physical capacity to do so (346). Aof critical care units, scheduled subcuta- Despite the preventable nature of hospital policy and procedures delineat-neous insulin which delivers basal, nutri- many inpatient episodes of hypoglyce- ing inpatient guidelines for CSII pumptional, and correction (supplemental) mia, institutions are more likely to have therapy are advisable. The availability ofcomponents is preferred. Prolonged ther- nursing protocols for the treatment of hy- hospital personnel with expertise in CSIIapy with sliding scale insulin (SSI) as the poglycemia than for its prevention. therapy is essential. It is important thatsole regimen is ineffective in the majority Tracking such episodes and analyzing nursing personnel document basal ratesof patients, increases risk of both hypo- their causes are important quality im- and bolus doses taken on a regular basisglycemia and hyperglycemia, and has re- provement activities (346). (at least daily).cently been shown to be associated withadverse outcomes in general surgery pa- 4. Diabetes care providers in the 6. DSME in the hospitaltients with type 2 diabetes (362). SSI is hospital Teaching diabetes self-management topotentially dangerous in type 1 diabetes Inpatient diabetes management may be patients in hospitals is a challenging task.(346). The reader is referred to several effectively championed and/or provided Patients are ill, under increased stress re-recent publications and reviews that de- by primary care physicians, endocrinolo- lated to their hospitalization and diagno-scribe currently available insulin prepara- gists, intensivists, or hospitalists. Involve- sis, and in an environment not conducivetions and protocols and provide guidance ment of appropriately trained specialists to learning. Ideally, people with diabetesin use of insulin therapy in specific clini- or specialty teams may reduce length of should be taught at a time and place con-cal settings including parenteral nutrition stay, improve glycemic control, and im- ducive to learning—as an outpatient in a(363), enteral tube feedings, and with prove outcomes (346). In the care of dia- recognized program of diabetes educa-high-dose glucocorticoid therapy (346). betes, implementation of standardized tion. There are no data on the safety and order sets for scheduled and correction- For the hospitalized patient, diabetesefficacy of oral agents and injectable non- dose insulin may reduce reliance on slid- “survival skills” education is generally ainsulin therapies such as GLP1 analogs ing-scale management. As hospitals move feasible approach. Patients and/or familyand pramlintide in the hospital. They are to comply with “meaningful use” regula- members receive sufficient informationgenerally considered to have a limited role tions for electronic health records, as and training to enable safe care at home.in the management of hyperglycemia in mandated by the Health Information Those newly diagnosed with diabetes orconjunction with acute illness. Continua- Technology Act, efforts should be made to who are new to insulin and/or blood glu-tion of these agents may be appropriate in assure that all components of structured in- cose monitoring need to be instructedselected stable patients who are expected sulin order sets are incorporated into elec- before discharge. Those patients hospital-to consume meals at regular intervals and tronic insulin order sets (364,365). ized because of a crisis related to diabetesthey may be initiated or resumed in antic- A team approach is needed to estab- management or poor care at home needipation of discharge once the patient is lish hospital pathways. To achieve glyce- education to prevent subsequent episodesclinically stable. Specific caution is re- mic targets associated with improved of hospitalization. An assessment of thecare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S45
    • Standards of Medical Careneed for a home health referral or referral blood, terms that are often used inter- ● Medication reconciliation: The pa-to an outpatient diabetes education pro- changeably and can lead to misinterpre- tient’s medications must be cross-gram should be part of discharge plan- tation. Most commercially available checked to ensure that no chronicning for all patients. capillary blood glucose meters introduce medications were stopped and to en- a correction factor of 1.12 to report a sure the safety of new prescriptions.7. MNT in the hospital “plasma adjusted” value (374). Whenever possible, prescriptions forThe goals of MNT are to optimize glyce- Significant discrepancies between new or changed medication should bemic control, to provide adequate calories capillary, venous, and arterial plasma filled and reviewed with the patient andto meet metabolic demands, and to create samples have been observed in patients family at or before dischargea discharge plan for follow-up care with low or high hemoglobin concentra- ● Structured discharge communication:(345,367). ADA does not endorse any tions, hypoperfusion, and the presence of Information on medication changes,single meal plan or specified percentages interfering substances particularly mal- pending tests and studies, and fol-of macronutrients, and the term “ADA tose, as contained in immunoglobulins low-up needs must be accurately anddiet” should no longer be used. Current (375). Analytical variability has been de- promptly communicated to outpatientnutrition recommendations advise indi- scribed with several POC meters (376). physicians, as soon as possible after dis-vidualization based on treatment goals, Increasingly, newer generation POC charge.physiologic parameters, and medication blood glucose meters correct for variationusage. Consistent carbohydrate meal in hematocrit and for interfering sub- Ideally the inpatient care providers orplans are preferred by many hospitals stances. Any glucose result that does not case managers/discharge planners willsince they facilitate matching the prandial correlate with the patient’s status should schedule follow-up visit(s) with the ap-insulin dose to the amount of carbohy- be confirmed through conventional labo- propriate professionals, including pri-drate consumed (368). Because of the ratory sampling of plasma glucose. The mary care provider, endocrinologist, andcomplexity of nutrition issues in the hos- FDA has become increasingly concerned diabetes educator (378).pital, a registered dietitian, knowledge- about the use of POC blood glucose An outpatient follow-up visit with theable and skilled in MNT, should serve as meters in the hospital and is presently re- primary care provider, endocrinologist,an inpatient team member. The dietitian viewing matters related to their use. or diabetes educator within 1 month ofis responsible for integrating information discharge is advised for all patients havingabout the patient’s clinical condition, eat- hyperglycemia in the hospital. Clear com-ing, and lifestyle habits and for establish- munication with outpatient providers ei- 9. Discharge planninging treatment goals in order to determine ther directly or via hospital discharge Transition from the acute care setting is aa realistic plan for nutrition therapy summaries facilitates safe transitions to high-risk time for all patients, not just(369,370). outpatient care. Providing information re- those with diabetes or new hyperglyce- garding the cause or the plan for deter- mia. Although there is an extensive liter-8. Bedside blood glucose monitoring mining the cause of hyperglycemia, ature concerning safe transition withinPoint-of-care (POC) blood glucose moni- related complications and comorbidities,toring performed at the bedside is used to and from the hospital, little of it is specific and recommended treatments can assistguide insulin dosing. In the patient who is to diabetes (377). It is important to re- outpatient providers as they assume on-receiving nutrition, the timing of glucose member that diabetes discharge planning going care.monitoring should match carbohydrate is not a separate entity, but part of an It is important that patients be pro-exposure. In the patient who is not receiv- overall discharge plan. As such, discharge vided with appropriate durable medicaling nutrition, glucose monitoring is per- planning begins at admission to the hos- equipment, medication, supplies, andformed every 4 to 6 h (371,372). More pital and is updated as projected patient prescriptions at the time of discharge infrequent blood glucose testing ranging needs change. order to avoid a potentially dangerous hi-from every 30 min to every 2 h is required Inpatients may be discharged to var- atus in care. These supplies/prescriptionsfor patients on intravenous insulin infu- ied settings, including home (with or should include:sions. without visiting nurse services), assisted Safety standards should be estab- living, rehabilitation, or skilled nursing ● Insulin (vials or pens) (if needed)lished for blood glucose monitoring, pro- facilities. The latter two sites are generally ● Syringes or pen needles (if needed)hibiting sharing of fingerstick lancing staffed by health professionals; therefore ● Oral medications (if needed)devices, lancets, and needles to reduce the diabetes discharge planning will be lim- ● Blood glucose meter and stripsrisk of transmission of blood borne dis- ited to communication of medication and ● Lancets and lancing deviceeases. Shared lancing devices carry essen- diet orders. For the patient who is dis- ● Urine ketone strips (type 1)tially the same risk as shared syringes and charged to assisted living or to home, the ● Glucagon emergency kit (insulin-needles (373). optimal program will need to consider the treated) Accuracy of blood glucose measure- type and severity of diabetes, the effects of ● Medical alert application/charmments using POC meters has limitations the patient’s illness on blood glucose lev-that must be considered. Although the els, and the capacities and desires of the IX. STRATEGIES FORFDA allows a 20% error for blood glu- patient. Smooth transition to outpatient IMPROVING DIABETEScose meters, questions about the appro- care should be ensured. The Agency for CARE — There has been steady im-priateness of these criteria have been Healthcare Research and Quality recom- provement in the proportion of diabeticraised (388). Glucose measures differ sig- mends that at a minimum, discharge patients achieving recommended levels ofnificantly between plasma and whole plans include: A1C, blood pressure, and LDL cholesterolS46 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statementin the last 10 years, both in primary care patients’ performance of appropriate self- ● Delivery of high-quality DSME, whichsettings and in endocrinology practices. management. has been shown to improve patient self-Mean A1C nationally has declined from A rapidly evolving literature suggests management, satisfaction, and glucose7.82% in 1999 –2000 to 7.18% in 2004 that there are three major strategies to control (115,387).based on National Health and Nutrition successfully improve the quality of diabe- ● Delivery of ongoing diabetes self-Examination Survey (NHANES) data tes care delivered by a team of providers. management support (DSMS) to ensure(379). This has been accompanied by im- NDEP maintains an online resource that gains achieved during DSME areprovements in lipids and blood pressure (www.betterdiabetescare.nih.gov) to help sustained (128 –129). National DSMEcontrol and led to substantial reductions health care professionals design and im- standards call for an integrated ap-in end-stage microvascular complications plement more effective health care deliv- proach that includes clinical contentin those with diabetes (380). Neverthe- ery systems for those with diabetes. and skills, behavioral strategies (goal-less, in some studies only 57.1% of adults Three specific objectives, with refer- setting, problem solving), and address-with diagnosed diabetes achieved an A1C ences to literature that outlines practical ing emotional concerns in each neededof 7%, only 45.5% had a blood pressure strategies to achieve each, are outlined be- curriculum content area. Provision of 130/80 mmHg, and just 46.5% had a low. continuing education and supporttotal cholesterol 200 mg/dl, with only (DSMS) improves maintenance of gains12.2% of people with diabetes achieving regardless of the educational methodol-all three treatment goals (381). Moreover, Objective 1 ogy (89). Provider and team behavior change: Fa- ● Provision of automated reminders viathere is persistent variation in quality ofdiabetes care across providers and across cilitate timely and appropriate intensifica- multiple communication channels topractice settings even after adjusting for tion of lifestyle and/or pharmaceutical various subgroups of diabetic patientspatient factors that indicates the potential therapy of patients who have not achieved (96).for substantial further improvements in beneficial levels of blood pressure, lipid,diabetes care. or glucose control. Objective 3 While numerous interventions to im- Change the system of care: Research onprove adherence to the recommended ● the comprehensive CCM suggests addi- Clinical information systems includingstandards have been implemented, a ma- tional strategies to improve diabetes care, registries that can prospectively iden- including the following:jor contributor to suboptimal care is a de- tify and track those requiring assess-livery system that too often is fragmented, ments and/or treatment modifications ● Basing care on consistent, evidence-lacks clinical information capabilities, of- by the team. ● based care guidelinesten duplicates services, and is poorly de- Electronic medical record-based clini- ● Redefining and expanding the roles ofsigned for the delivery of chronic care. cal decision support at the point of care, the clinic staff (382)The Chronic Care Model (CCM) includes both personalize and standardize care ● Collaborative, multidisciplinary teamssix core elements for the provision of op- and can be used by multiple providers to provide high-quality care and sup-timal care of patients with chronic dis- (383). ● port patients’ appropriate self-ease: 1) delivery system design (moving Use of checklists and/or flow sheets that managementfrom a reactive to a proactive care delivery mirror guidelines. ● ● Audit and feedback of process and out-system, where planned visits are coordi- Detailed treatment algorithms enabling come data to providers to encouragenated through a team-based approach; 2) multiple team members to “treat to tar- population-based care improvementself-management support; 3) decision get” and appropriately intensify ther- strategiessupport (basing care on consistent, effec- apy. ● ● Care management, one of the most ef-tive care guidelines); 4) clinical informa- Availability of care or disease manage- fective diabetes quality improvementtion systems (using registries that can ment services (384) by nurses, pharma- strategies to improve glycemic controlprovide patient-specific and population- cists, and other providers using (384).based support to the care team); 5) detailed algorithms often catalyzing re- ● Identifying and/or developing commu-community resources and policies (iden- duction in A1C, blood pressure, and nity resources and public policy thattifying or developing resources to support LDL cholesterol (385,386). support healthy lifestyleshealthy lifestyles); and 6) health systems ● Alterations in reimbursement that re-(to create a quality-oriented culture). Al- Objective 2 ward the provision of appropriate andterations in reimbursement that reward Patient behavior change: Implement a high-quality care and accommodate thethe provision of quality care, as defined by systematic approach to support patients’ need to personalize care goals, provid-the attainment of evidence-based quality behavior change efforts as needed includ- ing additional incentives to improve di-measures, will also be required to achieve ing 1) healthy lifestyle (physical activity, abetes care (382,388 –392)desired outcome goals. Redefinition of the healthy eating, nonuse of tobacco, weightroles of the clinic staff and promoting self- management, effective coping, medica- The most successful practices have an in-management on the part of the patient are tion taking and management); 2) preven- stitutional priority for quality of care, ex-fundamental to the successful implemen- tion of diabetes complications (screening panding the role of teams and staff,tation of the CCM (382). Collaborative, for eye, foot, and renal complications; im- redesigning their delivery system, activat-multidisciplinary teams are best suited to munizations); and 3) achievement of ap- ing and educating their patients, and us-provide such care for people with chronic propriate blood pressure, lipid, and ing electronic health record toolsconditions like diabetes and to facilitate glucose goals. (393,394). Recent initiatives such as thecare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S47
    • Standards of Medical CarePatient Centered Medical Home show peratore G, Williams DE, Albright AL. 1105promise in improving outcomes through A1C level and future risk of diabetes: a 19. Ramachandran A, Snehalatha C, Mary S,coordinated primary care and offer new systematic review. Diabetes Care 2010; Mukesh B, Bhaskar AD, Vijay V, Indianopportunities for team-based chronic dis- 33:1665–1673 Diabetes Prevention Programme (IDPP). 11. Selvin E, Steffes MW, Zhu H, Matsushita The Indian Diabetes Prevention Pro-ease care (395). K, Wagenknecht L, Pankow J, Coresh J, gramme shows that lifestyle modifica- It is clear that optimal diabetes man- Brancati FL. Glycated hemoglobin, dia- tion and metformin prevent type 2agement requires an organized, system- betes, and cardiovascular risk in nondi- diabetes in Asian Indian subjects withatic approach and involvement of a abetic adults. N Engl J Med 2010;362: impaired glucose tolerance (IDPP-1).coordinated team of dedicated health care 800 – 811 Diabetologia 2006;49:289 –297professionals working in an environment 12. Kahn R, Alperin P, Eddy D, Borch- 20. Johnson SL, Tabaei BP, Herman WH.where patient-centered high-quality care Johnsen K, Buse J, Feigelman J, Gregg E, The efficacy and cost of alternative strat-is a priority. Holman RR, Kirkman MS, Stern M, egies for systematic screening for type 2 Tuomilehto J, Wareham NJ. Age at initi- diabetes in the U.S. population 45–74 ation and frequency of screening to de- years of age. Diabetes Care 2005;References tect type 2 diabetes: a cost-effectiveness 28:307–311 1. American Diabetes Association: Medical analysis. Lancet 2010;375:1365–1374 21. Dabelea D, D’Agostino RB Jr, Mayer-Davis Management of Type 1 Diabetes. Alexan- 13. Knowler WC, Barrett-Connor E, Fowler EJ, Pettitt DJ, Imperatore G, Dolan LM, dria, VA, American Diabetes Associa- SE, Hamman RF, Lachin JM, Walker EA, Pihoker C, Hillier TA, Marcovina SM, tion, 2008 Nathan DM, Diabetes Prevention Pro- Linder B, Ruggiero AM, Hamman RF, 2. American Diabetes Association: Medical gram Research Group. Reduction in the SEARCH for Diabetes in Youth Study Management of Type 2 Diabetes. Alexan- incidence of type 2 diabetes with lifestyle Group. Testing the accelerator hypothesis: dria, VA, American Diabetes Associa- intervention or metformin. N Engl J Med body size, beta-cell function, and age at tion, 2008 2002;346:393– 403 onset of type 1 (autoimmune) diabetes. 3. American Diabetes Association: Intensive 14. Tuomilehto J, Lindstrom J, Eriksson JG, ¨ Diabetes Care 2006;29:290 –294 Diabetes Management. Alexandria, VA, Valle TT, Hamalainen H, Ilanne-Parikka ¨ ¨ ¨ 22. SEARCH for Diabetes in Youth Study American Diabetes Association, 2009 P, Keinanen-Kiukaanniemi S, Laakso M, ¨ Group, Liese AD, D’Agostino RB Jr, 4. American Diabetes Association: Diagno- Louheranta A, Rastas M, Salminen V, Hamman RF, Kilgo PD, Lawrence JM, sis and Classification of Diabetes Melli- Uusitupa M, Finnish Diabetes Preven- Liu LL, Loots B, Linder B, Marcovina S, tus. Diabetes Care 2010;33(Suppl. 1): tion Study Group. Prevention of type 2 Rodriguez B, Standiford D, Williams DE. S62–S69 diabetes mellitus by changes in lifestyle The burden of diabetes mellitus among 5. International Expert Committee: Inter- among subjects with impaired glucose US youth: prevalence estimates from the national Expert Committee report on the tolerance. N Engl J Med 2001;344: SEARCH for Diabetes in Youth Study. role of the A1C assay in the diagnosis of 1343–1350 Pediatrics 2006;118:1510 –1518 diabetes. Diabetes Care 2009;32:1327– 15. Pan XR, Li GW, Hu YH, Wang JX, Yang 23. American Diabetes Association: Type 2 1334 WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao diabetes in children and adolescents 6. Ziemer DC, Kolm P, Weintraub WS, HB, Liu PA, Jiang XG, Jiang YY, Wang JP, (Consensus Statement). Diabetes Care Vaccarino V, Rhee MK, Twombly JG, Zheng H, Zhang H, Bennett PH, Howard 2000;23:381–389 Narayan KM, Koch DD, Phillips LS. Glu- BV. Effects of diet and exercise in pre- 24. Lawrence JM, Contreras R, Chen W, cose-independent, black-white differ- venting NIDDM in people with impaired Sacks DA. Trends in the prevalence of ences in hemoglobin A1c levels: a cross- glucose tolerance. The Da Qing IGT and preexisting diabetes and gestational dia- sectional analysis of 2 studies. Ann Diabetes Study. Diabetes Care 1997;20: betes mellitus among a racially/ethni- Intern Med 2010;152:770 –777 537–544 cally diverse population of pregnant 7. Cowie CC, Rust KF, Byrd-Holt DD, 16. Buchanan TA, Xiang AH, Peters RK, Kjos women, 1999 –2005. Diabetes Care Gregg EW, Ford ES, Geiss LS, Bain- SL, Marroquin A, Goico J, Ochoa C, Tan 2008;31:899 –904 bridge KE, Fradkin JE. Prevalence of di- S, Berkowitz K, Hodis HN, Azen SP. 25. HAPO Study Cooperative Research abetes and high risk for diabetes using Preservation of pancreatic beta-cell Group, Metzger BE, Lowe LP, Dyer AR, A1C criteria in the U.S. population in function and prevention of type 2 diabe- Trimble ER, Chaovarindr U, Coustan 1988 –2006. Diabetes Care 2010;33: tes by pharmacological treatment of in- DR, Hadden DR, McCance DR, Hod M, 562–568 sulin resistance in high-risk hispanic McIntyre HD, Oats JJ, Persson B, Rogers 8. Expert Committee on the Diagnosis and women. Diabetes 2002;51:2796 –2803 MS, Sacks DA. Hyperglycemia and ad- Classification of Diabetes Mellitus: Re- 17. Chiasson JL, Josse RG, Gomis R, verse pregnancy outcomes. N Engl J Med port of the Expert Committee on the Di- Hanefeld M, Karasik A, Laakso M, 2008;358:1991–2002 agnosis and Classification of Diabetes STOP-NIDDM Trail Research Group. 26. International Association of Diabetes Mellitus. Diabetes Care 1997;20:1183– Acarbose for prevention of type 2 diabe- and Pregnancy Study Groups Consensus 1197 tes mellitus: the STOP-NIDDM random- Panel, Metzger BE, Gabbe SG, Persson B, 9. Genuth S, Alberti KG, Bennett P, Buse J, ised trial. Lancet 2002;359:2072–2077 Buchanan TA, Catalano PA, Damm P, Defronzo R, Kahn R, Kitzmiller J, 18. DREAM (Diabetes REduction Assess- Dyer AR, Leiva A, Hod M, Kitzmiler JL, Knowler WC, Lebovitz H, Lernmark A, ment with ramipril and rosiglitazone Lowe LP, McIntyre HD, Oats JJ, Omori Nathan D, Palmer J, Rizza R, Saudek C, Medication) Trial Investigators, Gerstein Y, Schmidt MI. International association Shaw J, Steffes M, Stern M, Tuomilehto J, HC, Yusuf S, Bosch J, Pogue J, Sheridan of diabetes and pregnancy study groups Zimmet P, Expert Committee on the Di- P, Dinccag N, Hanefeld M, Hoogwerf B, recommendations on the diagnosis and agnosis and Classification of Diabetes Laakso M, Mohan V, Shaw J, Zinman B, classification of hyperglycemia in preg- Mellitus: Follow-up report on the diag- Holman RR. Effect of rosiglitazone on nancy. Diabetes Care 2010;33:676 – 682 nosis of diabetes mellitus. Diabetes Care the frequency of diabetes in patients 27. Landon MB, Spong CY, Thom E, Car- 2003;26:3160 –3167 with impaired glucose tolerance or im- penter MW, Ramin SM, Casey B, Wap- 10. Zhang X, Gregg EW, Williamson DF, paired fasting glucose: a randomised ner RJ, Varner MW, Rouse DJ, Thorp JM Barker LE, Thomas W, Bullard KM, Im- controlled trial. Lancet 2006;368:1096 – Jr, Sciscione A, Catalano P, Harper M,S48 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement Saade G, Lain KY, Sorokin Y, Peaceman 162 46. Juvenile Diabetes Research Foundation AM, Tolosa JE, Anderson GB, Eunice 36. Torgerson JS, Hauptman J, Boldrin MN, Continuous Glucose Monitoring Study Kennedy Shriver National Institute of Sjostrom L. XENical in the prevention of ¨ ¨ Group: The effect of continuous glucose Child Health and Human Development diabetes in obese subjects (XENDOS) monitoring in well-controlled type 1 di- Maternal-Fetal Medicine Units Network. study: a randomized study of orlistat as abetes. Diabetes Care 2009;32:1378 – A multicenter, randomized trial of treat- an adjunct to lifestyle changes for the 1383 ment for mild gestational diabetes. prevention of type 2 diabetes in obese 47. DCCT: The effect of intensive treatment N Engl J Med 2009;361:1339 –1348 patients. Diabetes Care 2004;27:155– of diabetes on the development and pro- 28. Crowther CA, Hiller JE, Moss JR, 161 gression of long-term complications in McPhee AJ, Jeffries WS, Robinson JS, 37. Kawamori R, Tajima N, Iwamoto Y, insulin-dependent diabetes mellitus. Australian Carbohydrate Intolerance Kashiwagi A, Shimamoto K, Kaku K, Vo- The Diabetes Control and Complica- Study in Pregnant Women (ACHOIS) glibose Ph-3 Study Group. Voglibose for tions Trial Research Group. N Engl Trial Group. Effect of treatment of gesta- prevention of type 2 diabetes mellitus: a J Med 1993;329:977–986 tional diabetes mellitus on pregnancy randomised, double-blind trial in Japa- 48. Stratton IM, Adler AI, Neil HA, Mat- outcomes. N Engl J Med 2005; nese individuals with impaired glucose thews DR, Manley SE, Cull CA, Hadden 352:2477–2486 tolerance. Lancet 2009;373:1607–1614 D, Turner RC, Holman RR. Association 29. Kim C, Newton KM, Knopp RH. Gesta- 38. Gerstein HC. Point: If it is important to of glycaemia with macrovascular and tional diabetes and the incidence of type prevent type 2 diabetes, it is important to microvascular complications of type 2 2 diabetes: a systematic review. Diabetes consider all proven therapies within a diabetes (UKPDS 35): prospective ob- Care 2002;25:1862–1868 comprehensive approach. Diabetes Care servational study. BMJ 2000;321:405– 30. Li G, Zhang P, Wang J, Gregg EW, Yang 2007;30:432– 434 412 W, Gong Q, Li H, Li H, Jiang Y, An Y, 39. Nathan DM, Davidson MB, DeFronzo 49. Cagliero E, Levina EV, Nathan DM. Im- Shuai Y, Zhang B, Zhang J, Thompson RA, Heine RJ, Henry RR, Pratley R, Zin- mediate feedback of HbA1c levels im- TJ, Gerzoff RB, Roglic G, Hu Y, Bennett man B, American Diabetes Association. proves glycemic control in type 1 and PH. The long-term effect of lifestyle in- Impaired fasting glucose and impaired insulin-treated type 2 diabetic patients. terventions to prevent diabetes in the glucose tolerance: implications for care. Diabetes Care 1999;22:1785–1789 China Da Qing Diabetes Prevention Diabetes Care 2007;30:753–759 50. Miller CD, Barnes CS, Phillips LS, Zi- Study: a 20-year follow-up study. Lancet 40. Welschen LM, Bloemendal E, Nijpels G, emer DC, Gallina DL, Cook CB, Mary- 2008;371:1783–1789 Dekker JM, Heine RJ, Stalman WA, man SD, El-Kebbi IM. Rapid A1c 31. Lindstrom J, Ilanne-Parikka P, Peltonen ¨ Bouter LM. Self-monitoring of blood availability improves clinical decision- M, Aunola S, Eriksson JG, Hemio K, Ha- ¨ ¨ glucose in patients with type 2 diabetes making in an urban primary care clinic. malainen H, Harkonen P, Keinanen- ¨ ¨ ¨ ¨ ¨ who are not using insulin: a systematic Diabetes Care 2003;26:1158 –1163 Kiukaanniemi S, Laakso M, Louheranta review. Diabetes Care 2005;28:1510 – 51. Nathan DM, Kuenen J, Borg R, Zheng H, A, Mannelin M, Paturi M, Sundvall J, 1517 Schoenfeld D, Heine RJ, A1c-Derived Valle TT, Uusitupa M, Tuomilehto J, 41. Farmer A, Wade A, Goyder E, Yudkin P, Average Glucose Study Group. Translat- Finnish Diabetes Prevention Study French D, Craven A, Holman R, Kin- ing the A1C assay into estimated average Group. Sustained reduction in the inci- month AL, Neil A. Impact of self moni- glucose values. Diabetes Care 2008;31: dence of type 2 diabetes by lifestyle in- toring of blood glucose in the 1473–1478 tervention: follow-up of the Finnish management of patients with non-insu- 52. Rohlfing CL, Wiedmeyer HM, Little RR, Diabetes Prevention Study. Lancet 2006; lin treated diabetes: open parallel group England JD, Tennill A, Goldstein DE. 368:1673–1679 randomised trial. BMJ 2007;335:132 Defining the relationship between 32. Diabetes Prevention Program Research 42. O’Kane MJ, Bunting B, Copeland M, plasma glucose and HbA(1c): analysis of Group, Knowler WC, Fowler SE, Ham- Coates VE, ESMON study group. Effi- glucose profiles and HbA(1c) in the Di- man RF, Christophi CA, Hoffman HJ, cacy of self monitoring of blood glucose abetes Control and Complications Trial. Brenneman AT, Brown-Friday JO, Gold- in patients with newly diagnosed type 2 Diabetes Care 2002;25:275–278 berg R, Venditti E, Nathan DM. 10-year diabetes (ESMON study): randomised 53. Diabetes Research in Children Network follow-up of diabetes incidence and controlled trial. BMJ 2008;336:1174 – (DirecNet) Study Group, Wilson DM, weight loss in the Diabetes Prevention 1177 Kollman. Relationship of A1C to glucose Program Outcomes Study. Lancet 2009; 43. Simon J, Gray A, Clarke P, Wade A, Neil concentrations in children with type 1 374:1677–1686 A, Farmer A, Diabetes Glycaemic Educa- diabetes: assessments by high-frequency 33. Herman WH, Hoerger TJ, Brandle M, tion and Monitoring Trial Group. Cost glucose determinations by sensors. Dia- Hicks K, Sorensen S, Zhang P, Hamman effectiveness of self monitoring of blood betes Care 2008;31:381–385 RF, Ackermann RT, Engelgau MM, Rat- glucose in patients with non-insulin 54. Ohkubo Y, Kishikawa H, Araki E, Miyata ner RE, Diabetes Prevention Program treated type 2 diabetes: economic evalu- T, Isami S, Motoyoshi S, Kojima Y, Fu- Research Group. The cost-effectiveness ation of data from the DiGEM trial. BMJ ruyoshi N, Shichiri M. Intensive insulin of lifestyle modification or metformin in 2008;336:1177–1180 therapy prevents the progression of dia- preventing type 2 diabetes in adults with 44. Sacks DB, Bruns DE, Goldstein DE, Ma- betic microvascular complications in impaired glucose tolerance. Ann Intern claren NK, McDonald JM, Parrott M. Japanese patients with non-insulin-de- Med 2005;142:323–332 Guidelines and recommendations for pendent diabetes mellitus: a randomized 34. Ackermann RT, Finch EA, Brizendine E, laboratory analysis in the diagnosis and prospective 6-year study. Diabetes Res Zhou H, Marrero DG. Translating the management of diabetes mellitus. Clin Clin Pract 1995;28:103–117 Diabetes prevention Program into the Chem 2002;48:436 – 472 55. UKPDS: Effect of intensive blood-glu- community: the DEPLOY Pilot Study. 45. The Juvenile Diabetes Research Founda- cose control with metformin on compli- Am J Prev Med 2008;35:357–363 tion Continuous Glucose Monitoring cations in overweight patients with type 35. Kosaka K, Noda M, Kuzuya T. Preven- Study Group: Continuous glucose mon- 2 diabetes (UKPDS 34). UK Prospective tion of type 2 diabetes by lifestyle inter- itoring and intensive treatment of type 1 Diabetes Study (UKPDS) Group. Lancet vention: a Japanese trial in IGT males. diabetes. N Engl J Med 2008;359:1464 – 1998;352:854 – 865 Diabetes Res Clin Pract 2005;67:152– 1476 56. UKPDS: Intensive blood-glucose controlcare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S49
    • Standards of Medical Care with sulphonylureas or insulin com- Fine LJ. Effects of medical therapies on Diabetes Investigators. Epidemiologic pared with conventional treatment and retinopathy progression in type 2 diabe- relationships between A1C and all-cause risk of complications in patients with tes. N Engl J Med 2010;363:233–244 mortality during a median 3.4-year fol- type 2 diabetes (UKPDS 33). UK Pro- 65. Action to Control Cardiovascular Risk in low-up of glycemic treatment in the AC- spective Diabetes Study (UKPDS) Diabetes Study Group, Gerstein HC, CORD trial. Diabetes Care 2010;33: Group. Lancet 1998;352:837– 853 Miller ME, Byington RP, Goff DC Jr, Big- 983–990 57. DCCT-EDIC: Retinopathy and ne- ger JT, Buse JB, Cushman WC, Genuth 72. Reaven PD, Moritz TE, Schwenke DC, phropathy in patients with type 1 diabe- S, Ismail-Beigi F, Grimm RH Jr, Probst- Anderson RJ, Criqui M, Detrano R, tes four years after a trial of intensive field JL, Simons-Morton DG, Friedewald Emanuele N, Kayshap M, Marks J, Mu- therapy. The Diabetes Control and Com- WT. Effects of intensive glucose lower- daliar S, Rao RH, Shah JH, Goldman S, plications Trial/Epidemiology of Diabe- ing in type 2 diabetes. N Engl J Med Reda DJ, McCarren M, Abraira C, Duck- tes Interventions and Complications 2008;358:2545–2559 worth W: Intensive Glucose Lowering Research Group. N Engl J Med 2000; 66. Selvin E, Marinopoulos S, Berkenblit G, Therapy Reduces Cardiovascular Dis- 342:381–389 Rami T, Brancati FL, Powe NR, Golden ease Events in VADT Participants with 58. Martin CL, Albers J, Herman WH, SH. Meta-analysis: glycosylated hemo- Lower Calcified Coronary Atherosclero- Cleary P, Waberski B, Greene DA, globin and cardiovascular disease in di- sis. Diabetes published online August 3, Stevens MJ, Feldman EL, DCCT/EDIC abetes mellitus. Ann Intern Med 2004; 2009 Research Group. Neuropathy among the 141:421– 431 73. Turnbull FM, Abraira C, Anderson RJ, diabetes control and complications trial 67. Stettler C, Allemann S, Juni P, Cull CA, ¨ Byington RP, Chalmers JP, Duckworth cohort 8 years after trial completion. Di- Holman RR, Egger M, Krahenbuhl S, ¨ ¨ WC, Evans GW, Gerstein HC, Holman abetes Care 2006;29:340 –344 Diem P. Glycemic control and macro- RR, Moritz TE, Neal BC, Ninomiya T, 59. Holman RR, Paul SK, Bethel MA, Mat- vascular disease in types 1 and 2 diabetes Patel AA, Paul SK, Travert F, Woodward thews DR, Neil HA: 10-Year Follow-up mellitus: Meta-analysis of randomized M: Intensive glucose control and macro- of intensive glucose control in type 2 di- trials. Am Heart J 2006;152:27–38 vascular outcomes in type 2 diabetes. abetes. N Engl J Med 2008;359:1577– 68. Nathan DM, Cleary PA, Backlund JY, Diabetologia 2009;52:2288 –2298 1589 Genuth SM, Lachin JM, Orchard TJ, 74. American Diabetes Association: Post- 60. Duckworth W, Abraira C, Moritz T, Raskin P, Zinman B, Diabetes Control prandial blood glucose (Consensus Reda D, Emanuele N, Reaven PD, Zieve and Complications Trial/Epidemiology Statement). Diabetes Care 2001;24: FJ, Marks J, Davis SN, Hayward R, War- of Diabetes Interventions and Complica- 775–778 ren SR, Goldman S, McCarren M, Vitek tions (DCCT/EDIC) Study Research 75. Ceriello A, Taboga C, Tonutti L, Qua- ME, Henderson WG, Huang GD, VADT Group. Intensive diabetes treatment and gliaro L, Piconi L, Bais B, Da Ros R, Investigators. Glucose control and vas- cardiovascular disease in patients with Motz E. Evidence for an independent cular complications in veterans with type 1 diabetes. N Engl J Med 2005;353: and cumulative effect of postprandial type 2 diabetes. N Engl J Med 2009;360: 2643–2653 hypertriglyceridemia and hyperglyce- 129 –139 69. Diabetes Control and Complications mia on endothelial dysfunction and 61. Moritz T, Duckworth W, Abraira C. Vet- Trial/Epidemiology of Diabetes Inter- oxidative stress generation: effects of erans Affairs diabetes trial– corrections. ventions and Complications (DCCT/ short- and long-term simvastatin treat- N Engl J Med 2009;361:1024 –1025 EDIC) Research Group, Nathan DM, ment. Circulation 2002;106:1211– 62. ADVANCE Collaborative Group, Patel Zinman B, Cleary PA, Backlund JY, Ge- 1218 A, MacMahon S, Chalmers J, Neal B, Bil- nuth S, Miller R, Orchard TJ. Modern- 76. Raz I, Wilson PW, Strojek K, Kowalska I, lot L, Woodward M, Marre M, Cooper day clinical course of type 1 diabetes Bozikov V, Gitt AK, Jermendy G, Cam- M, Glasziou P, Grobbee D, Hamet P, mellitus after 30 years’ duration: the di- paigne BN, Kerr L, Milicevic Z, Jacober Harrap S, Heller S, Liu L, Mancia G, Mo- abetes control and complications trial/ SJ. Effects of prandial versus fasting gly- gensen CE, Pan C, Poulter N, Rodgers A, epidemiology of diabetes interventions cemia on cardiovascular outcomes in Williams B, Bompoint S, de Galan BE, and complications and Pittsburgh epide- type 2 diabetes: the HEART2D trial. Di- Joshi R, Travert F. Intensive blood glu- miology of diabetes complications expe- abetes Care 2009;32:381–386 cose control and vascular outcomes in rience (1983–2005). Arch Intern Med 77. Metzger BE, Buchanan TA, Coustan DR, patients with type 2 diabetes. N Engl 2009;169:1307–1316 de Leiva A, Dunger DB, Hadden DR, J Med 2008;358:2560 –2572 70. Skyler JS, Bergenstal R, Bonow RO, Buse Hod M, Kitzmiller JL, Kjos SL, Oats JN, 63. Ismail-Beigi F, Craven T, Banerji MA, J, Deedwania P, Gale EA, Howard BV, Pettitt DJ, Sacks DA, Zoupas C. Sum- Basile J, Calles J, Cohen RM, Cuddihy R, Kirkman MS, Kosiborod M, Reaven P, mary and recommendations of the Fifth Cushman WC, Genuth S, Grimm RH Jr, Sherwin RS, American Diabetes Associ- International Workshop-Conference on Hamilton BP, Hoogwerf B, Karl D, Katz ation, American College of Cardiology Gestational Diabetes Mellitus. Diabetes L, Krikorian A, O’Connor P, Pop-Busui Foundation, American Heart Associa- Care 2007;30(Suppl. 2):S251–S260 R, Schubart U, Simmons D, Taylor H, tion. Intensive glycemic control and the 78. Kitzmiller JL, Block JM, Brown FM, Thomas A, Weiss D, Hramiak I, AC- prevention of cardiovascular events: im- Catalano PM, Conway DL, Coustan DR, CORD trial group. Effect of intensive plications of the ACCORD, ADVANCE, Gunderson EP, Herman WH, Hoffman treatment of hyperglycaemia on micro- and VA diabetes trials: a position state- LD, Inturrisi M, Jovanovic LB, Kjos SI, vascular outcomes in type 2 diabetes: an ment of the American Diabetes Associa- Knopp RH, Montoro MN, Ogata ES, analysis of the ACCORD randomised tion and a scientific statement of the Paramsothy P, Reader DM, Rosenn BM, trial. Lancet 2010;376:419 – 430 American College of Cardiology Foun- Thomas AM, Kirkman MS. Managing 64. ACCORD Study Group, ACCORD Eye dation and the American Heart Associa- preexisting diabetes for pregnancy: sum- Study Group, Chew EY, Ambrosius WT, tion. Diabetes Care 2009;32:187–192 mary of evidence and consensus recom- Davis MD, Danis RP, Gangaputra S, 71. Riddle MC, Ambrosius WT, Brillon DJ, mendations for care. Diabetes Care Greven CM, Hubbard L, Esser BA, Lo- Buse JB, Byington RP, Cohen RM, Goff 2008;31:1060 –1079 vato JF, Perdue LH, Goff DC Jr, Cush- DC Jr, Malozowski S, Margolis KL, 79. DeWitt DE, Hirsch IB. Outpatient insu- man WC, Ginsberg HN, Elam MB, Probstfield JL, Schnall A, Seaquist ER, lin therapy in type 1 and type 2 diabetes Genuth S, Gerstein HC, Schubart U, Action to Control Cardiovascular Risk in mellitus: scientific review. JAMA 2003;S50 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement 289:2254 –2264 91. Glasgow RE, Peeples M, Skovlund SE. tions for older, African American, or 80. Rosenstock J, Dailey G, Massi-Benedetti Where is the patient in diabetes perfor- Latino adults. Diabetes Educ 2003;29: M, Fritsche A, Lin Z, Salzman A. Re- mance measures? The case for including 467–479 duced hypoglycemia risk with insulin patient-centered and self-management 103. Chodosh J, Morton SC, Mojica W, Ma- glargine: a meta-analysis comparing in- measures. Diabetes Care 2008;31: glione M, Suttorp MJ, Hilton L, Rhodes sulin glargine with human NPH insulin 1046 –1050 S, Shekelle P. Meta-analysis: chronic in type 2 diabetes. Diabetes Care 2005; 92. Barker JM, Goehrig SH, Barriga K, Hoff- disease self-management programs for 28:950 –955 man M, Slover R, Eisenbarth GS, Norris older adults. Ann Intern Med 2005;143: 81. Mooradian AD, Bernbaum M, Albert SG. JM, Klingensmith GJ, Rewers M, DAISY 427– 438 Narrative review: a rational approach to study. Clinical characteristics of chil- 104. Piette JD, Glasgow RE: Sttategies for im- starting insulin therapy. Ann Intern Med dren diagnosed with type 1 diabetes proving behavioral and health outcomes 2006;145:125–134 through intensive screening and follow- among people with diabetes:self man- 82. Nathan DM, Buse JB, Davidson MB, Fer- up. Diabetes Care 2004;27:1399 –1404 agemnt education. In Evidence-Based Di- rannini E, Holman RR, Sherwin R, Zin- 93. Cochran J, Conn VS. Meta-analysis of abetes Care. Gerstein HC, Hayes.R.B., man B, American Diabetes Association, quality of life outcomes following diabe- Eds. Ontario, Canada, BC Decker, 2000 European Association for Study of Dia- tes self-management training. Diabetes 105. Peyrot M, Rubin RR. Behavioral and psy- betes. Medical management of hypergly- Educ 2008;34:815– 823 chosocial interventions in diabetes: a cemia in type 2 diabetes: a consensus 94. Fisher EB, Thorpe CT, Devellis BM, De- conceptual review. Diabetes Care 2007; algorithm for the initiation and adjust- vellis RF. Healthy coping, negative emo- 30:2433–2440 ment of therapy: a consensus statement tions, and diabetes management: a 106. Anderson DR, Christison-Legay J, Proctor- of the American Diabetes Association systematic review and appraisal. Diabe- Gray E. Self-Management goal setting in a and the European Association for the tes Educ 2007;33:1080 –1103 community health center: the impact of goal Study of Diabetes. Diabetes Care 2009; 95. Robbins JM, Thatcher GE, Webb DA, attainment on diabetes outcomes. Diabetes 32:193–203 Valdmanis VG. Nutritionist visits, diabe- Spectrum 2010;23:97–106 83. Norris SL, Engelgau MM, Narayan KM. tes classes, and hospitalization rates and 107. Rickheim PL, Weaver TW, Flader JL, Effectiveness of self-management train- charges: the Urban Diabetes Study. Dia- Kendall DM. Assessment of group versus ing in type 2 diabetes: a systematic re- betes Care 2008;31:655– 660 individual diabetes education: a ran- view of randomized controlled trials. 96. Renders CM, Valk GD, Griffin SJ, Wag- domized study. Diabetes Care 2002;25: Diabetes Care 2001;24:561–587 ner EH, Eijk Van JT, Assendelft WJ. In- 269 –274 84. Norris SL, Lau J, Smith SJ, Schmid CH, terventions to improve the management 108. Trento M, Passera P, Borgo E, Tomalino Engelgau MM. Self-management educa- of diabetes in primary care, outpatient, M, Bajardi M, Cavallo F, Porta M. A tion for adults with type 2 diabetes: a meta- and community settings: a systematic re- 5-year randomized controlled study of analysis of the effect on glycemic control. view. Diabetes Care 2001;24:1821– learning, problem solving ability, and Diabetes Care 2002;25:1159 –1171 1833 quality of life modifications in people 85. Gary TL, Genkinger JM, Guallar E, Pey- 97. Polonsky WH, Earles J, Smith S, Pease with type 2 diabetes managed by group rot M, Brancati FL. Meta-analysis of ran- DJ, Macmillan M, Christensen R, Taylor care. Diabetes Care 2004;27:670 – 675 domized educational and behavioral T, Dickert J, Jackson RA. Integrating 109. Deakin T, McShane CE, Cade JE, Wil- interventions in type 2 diabetes. Diabe- medical management with diabetes self- liams RD: Group based training for self- tes Educ 2003;29:488 –501 management training: a randomized management strategies in people with 86. Steed L, Cooke D, Newman S. A system- control trial of the Diabetes Outpatient type 2 diabetes mellitus. Cochrane Da- atic review of psychosocial outcomes fol- Intensive Treatment program. Diabetes tabase Syst Rev CD003417, 2005 lowing education, self-management and Care 2003;26:3048 –3053 110. Duke SA, Colagiuri S, Colagiuri R: Indi- psychological interventions in diabetes 98. Anderson RM, Funnell MM, Nwankwo vidual patient education for people with mellitus. Patient Educ Couns 2003;51: R, Gillard ML, Oh M, Fitzgerald JT. Eval- type 2 diabetes mellitus. Cochrane Da- 5–15 uating a problem-based empowerment tabase Syst Rev CD005268, 2009 87. Ellis SE, Speroff T, Dittus RS, Brown A, program for African Americans with di- 111. Heisler M, Vijan S, Makki F, Piette JD. Pichert JW, Elasy TA. Diabetes patient abetes: results of a randomized con- Diabetes control with reciprocal peer education: a meta-analysis and meta-re- trolled trial. Ethn Dis 2005;15:671– 678 support versus nurse care management: gression. Patient Educ Couns 2004;52: 99. Brown SA, Blozis SA, Kouzekanani K, a randomized trial. Ann Intern Med 97–105 Garcia AA, Winchell M, Hanis CL. Dos- 2010;153:507–515 88. Warsi A, Wang PS, LaValley MP, Avorn age effects of diabetes self-management 112. Heisler M. Different models to mobilize J, Solomon DH. Self-management edu- education for Mexican Americans: the peer support to improve diabetes self- cation programs in chronic disease: a Starr County Border Health Initiative. management and clinical outcomes: systematic review and methodological Diabetes Care 2005;28:527–532 evidence, logistics, evaluation consider- critique of the literature. Arch Intern 100. Glazier RH, Bajcar J, Kennie NR, Willson ations and needs for future research. Med 2004;164:1641–1649 K. A systematic review of interventions Fam Pract 2010;27(Suppl. 1):i23–i32 89. Funnell MM, Brown TL, Childs BP, Haas to improve diabetes care in socially dis- 113. Foster G, Taylor SJ, Eldridge SE, Ramsay LB, Hosey GM, Jensen B, Maryniuk M, advantaged populations. Diabetes Care J, Griffiths CJ: Self-management educa- Peyrot M, Piette JD, Reader D, Siminerio 2006;29:1675–1688 tion programmes by lay leaders for peo- LM, Weinger K, Weiss MA. National 101. Hawthorne K, Robles Y, Cannings-John ple with chronic conditions. Cochrane standards for diabetes self-management R, Edwards AG: Culturally appropriate Database Syst Rev CD005108, 2007 education. Diabetes Care 2007;30: health education for type 2 diabetes mel- 114. Norris SL, Chowdhury FM, Van Le K, 1630 –1637 litus in ethnic minority groups. Co- Horsley T, Brownstein JN, Zhang X, Jack 90. Mulcahy K, Maryniuk M, Peeples M, chrane Database Syst Rev CD006424, L Jr, Satterfield DW. Effectiveness of Peyrot M, Tomky D, Weaver T, Yarbor- 2008 community health workers in the care of ough P. Diabetes self-management edu- 102. Sarkisian CA, Brown AF, Norris KC, persons with diabetes. Diabet Med cation core outcomes measures. Wintz RL, Mangione CM. A systematic 2006;23:544 –556 Diabetes Educ 2003;29:768 –784 review of diabetes self-care interven- 115. Duncan I, Birkmeyer C, Coughlin S, Licare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S51
    • Standards of Medical Care QE, Sherr D, Boren S. Assessing the 126. Appel LJ, Moore TJ, Obarzanek E, peland MA, Foreyt JP, Graves K, Haffner value of diabetes education. Diabetes Vollmer WM, Svetkey LP, Sacks FM, SM, Harrison B, Hill JO, Horton ES, Ja- Educ 2009;35:752–760 Bray GA, Vogt TM, Cutler JA, kicic J, Jeffery RW, Johnson KC, Kahn S,116. Bantle JP, Wylie-Rosett J, Albright AL, Windhauser MM, Lin PH, Karanja N. A Kelley DE, Kitabchi AE, Knowler WC, Apovian CM, Clark NG, Franz MJ, clinical trial of the effects of dietary pat- Lewis CE, Maschak-Carey BJ, Montgom- Hoogwerf BJ, Lichtenstein AH, Mayer- terns on blood pressure. DASH Collab- ery B, Nathan DM, Patricio J, Peters A, Davis E, Mooradian AD, Wheeler ML. orative Research Group. N Engl J Med Redmon JB, Reeves RS, Ryan DH, Saf- Nutrition recommendations and inter- 1997;336:1117–1124 ford M, Van Dorsten B, Wadden TA, ventions for diabetes: a position state- 127. Norris SL, Zhang X, Avenell A, Gregg E, Wagenknecht L, Wesche-Thobaben J, ment of the American Diabetes Association. Bowman B, Schmid CH, Lau J. Long- Wing RR, Yanovski SZ. Reduction in Diabetes Care 2008;31(Suppl. 1):S61–S78 term effectiveness of weight-loss inter- weight and cardiovascular disease risk117. DAFNE Study Group. Training in flexi- ventions in adults with prediabetes: a factors in individuals with type 2 diabe- ble, intensive insulin management to en- review. Am J Prev Med 2005;28:126 – tes: one-year results of the look AHEAD able dietary freedom in people with type 139 trial. Diabetes Care 2007;30:1374 – 1 diabetes: dose adjustment for normal 128. Klein S, Sheard NF, Pi-Sunyer X, Daly A, 1383 eating (DAFNE) randomised controlled Wylie-Rosett J, Kulkarni K, Clark NG, 135. Look AHEAD Research Group, Wing trial. BMJ 2002;325:746 American Diabetes Association, North RR: Long-term effects of a lifestyle inter-118. Franz MJ, Monk A, Barry B, McClain K, American Association for the Study of vention on weight and cardiovascular Weaver T, Cooper N, Upham P, Ber- Obesity, American Society for Clinical risk factors in individuals with type 2 genstal R, Mazze RS. Effectiveness of Nutrition. Weight management through diabetes mellitus: four-year results of the medical nutrition therapy provided by lifestyle modification for the prevention Look AHEAD trial. Arch Intern Med dietitians in the management of non- and management of type 2 diabetes: ra- 2010;170:1566 –1575 insulin-dependent diabetes mellitus: a tionale and strategies: a statement of 136. Foster GD, Wyatt HR, Hill JO, randomized, controlled clinical trial. the American Diabetes Association, the McGuckin BG, Brill C, Mohammed BS, J Am Diet Assoc 1995;95:1009 – North American Association for the Szapary PO, Rader DJ, Edman JS, Klein 1017 Study of Obesity, and the American So- S. A randomized trial of a low-carbohy-119. Goldhaber-Fiebert JD, Goldhaber-Fiebert ciety for Clinical Nutrition. Diabetes drate diet for obesity. N Engl J Med SN, Tristan ML, Nathan DM. Randomized ´ Care 2004;27:2067–2073 2003;348:2082–2090 controlled community-based nutrition 129. Norris SL, Zhang X, Avenell A, Gregg E, 137. Stern L, Iqbal N, Seshadri P, Chicano and exercise intervention improves glyce- Schmid CH, Kim C, Lau J. Efficacy of KL, Daily DA, McGrory J, Williams M, mia and cardiovascular risk factors in type pharmacotherapy for weight loss in Gracely EJ, Samaha FF. The effects of 2 diabetic patients in rural Costa Rica. Di- adults with type 2 diabetes mellitus: low-carbohydrate versus conventional abetes Care 2003;26:24 –29 a meta-analysis. Arch Intern Med 2004; weight loss diets in severely obese120. Lemon CC, Lacey K, Lohse B, Hubacher 164:1395–1404 adults: one-year follow-up of a random- DO, Klawitter B, Palta M. Outcomes 130. Wolf AM, Conaway MR, Crowther JQ, ized trial. Ann Intern Med 2004; monitoring of health, behavior, and Hazen KY, L Nadler J, Oneida B, Bovb- 140:778 –785 quality of life after nutrition intervention jerg VE, Improving Control with Activ- 138. Foster GD, Wyatt HR, Hill JO, Makris in adults with type 2 diabetes. J Am Diet ity and Nutrition (ICAN) Study. AP, Rosenbaum DL, Brill C, Stein RI, Assoc 2004;104:1805–1815 Translating lifestyle intervention to Mohammed BS, Miller B, Rader DJ, Ze-121. Miller CK, Edwards L, Kissling G, San- practice in obese patients with type 2 mel B, Wadden TA, Tenhave T, New- ville L. Nutrition education improves diabetes: Improving Control with Activ- comb CW, Klein S. Weight and metabolic outcomes among older adults ity and Nutrition (ICAN) study. Diabe- metabolic outcomes after 2 years on a with diabetes mellitus: results from a tes Care 2004;27:1570 –1576 low-carbohydrate versus low-fat diet: a randomized controlled trial. Prev Med 131. Manning RM, Jung RT, Leese GP, New- randomized trial. Ann Intern Med 2010; 2002;34:252–259 ton RW. The comparison of four weight 153:147–157122. Wilson C, Brown T, Acton K, Gilliland S. reduction strategies aimed at overweight 139. Gardner CD, Kiazand A, Alhassan S, Effects of clinical nutrition education patients with diabetes mellitus: four- Kim S, Stafford RS, Balise RR, Kraemer and educator discipline on glycemic year follow-up. Diabet Med 1998;15: HC, King AC. Comparison of the Atkins, control outcomes in the Indian health 497–502 Zone, Ornish, and LEARN diets for service. Diabetes Care 2003;26:2500 – 132. Franz MJ, VanWormer JJ, Crain AL, change in weight and related risk factors 2504 Boucher JL, Histon T, Caplan W, Bow- among overweight premenopausal123. Graber AL, Elasy TA, Quinn D, Wolff K, man JD, Pronk NP. Weight-loss out- women: the A TO Z Weight Loss Study: Brown A. Improving glycemic control in comes: a systematic review and meta- a randomized trial. JAMA 2007;297: adults with diabetes mellitus: shared re- analysis of weight-loss clinical trials with 969 –977 sponsibility in primary care practices. a minimum 1-year follow-up. J Am Diet 140. Nordmann AJ, Nordmann A, Briel M, South Med J 2002;95:684 – 690 Assoc 2007;107:1755–1767 Keller U, Yancy WS, Jr, Brehm BJ,124. Gaetke LM, Stuart MA, Truszczynska H. 133. Salas-Salvado J, Bullo M, Babio N, Mar- Bucher HC. Effects of low-carbohydrate A single nutrition counseling session tinez-Gonzalez MA, Ibarrola-Jurado N, vs low-fat diets on weight loss and car- with a registered dietitian improves Basora J, Estruch R, Covas MI, Corella D, diovascular risk factors: a meta-analysis short-term clinical outcomes for rural Aros F, Ruiz-Gutierrez V, Ros E: Reduc- of randomized controlled trials. Arch In- Kentucky patients with chronic diseases. tion in the Incidence of Type 2 Diabetes tern Med 2006;166:285–293 J Am Diet Assoc 2006;106:109 –112 with the Mediterranean Diet: Results of 141. Shai I, Schwarzfuchs D, Henkin Y, Sha-125. Van Horn L, McCoin M, Kris-Etherton the PREDIMED-Reus Nutrition Inter- har DR, Witkow S, Greenberg I, Golan PM, Burke F, Carson JA, Champagne vention Randomized Trial. Diabetes R, Fraser D, Bolotin A, Vardi H, Tangi- CM, Karmally W, Sikand G. The evi- Care 2010;34:14 –19 Rozental O, Zuk-Ramot R, Sarusi B, dence for dietary prevention and treat- 134. Look AHEAD Research Group, Pi-Su- Brickner D, Schwartz Z, Sheiner E, ment of cardiovascular disease. J Am nyer X, Blackburn G, Brancati FL, Bray Marko R, Katorza E, Thiery J, Fiedler Diet Assoc 2008;108:287–331 GA, Bright R, Clark JM, Curtis JM, Es- GM, Bluher M, Stumvoll M, Stampfer ¨S52 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement MJ, Dietary Intervention Randomized litus. Arch Phys Med Rehabil 2005;86: Alexandria, VA, American Diabetes As- Controlled Trial (DIRECT) Group. 1527–1533 sociation, 2002, p. 433– 449 Weight loss with a low-carbohydrate, 151. Dunstan DW, Daly RM, Owen N, Jolley 162. Anderson RJ, Grigsby AB, Freedland KE, Mediterranean, or low-fat diet. N Engl D, De Courten M, Shaw J, Zimmet P. de Groot M, McGill JB, Clouse RE, Lust- J Med 2008;359:229 –241 High-intensity resistance training im- man PJ. Anxiety and poor glycemic con-142. Institute of Medicine: DIetary Reference proves glycemic control in older patients trol: a meta-analytic review of the Intakes: Energy, Carbohydrate, Fiber, Fat, with type 2 diabetes. Diabetes Care literature. Int J Psychiatry Med 2002;32: Fatty Acids, Cholesterol, Protein, and 2002;25:1729 –1736 235–247 Amino Acids. Washington, D.C., Na- 152. Castaneda C, Layne JE, Munoz-Orians 163. Delahanty LM, Grant RW, Wittenberg E, tional Academies Press, 2002 L, Gordon PL, Walsmith J, Foldvari M, Bosch JL, Wexler DJ, Cagliero E, Meigs143. Barnard ND, Cohen J, Jenkins DJ, Turn- Roubenoff R, Tucker KL, Nelson ME. A JB. Association of diabetes-related emo- er-McGrievy G, Gloede L, Jaster B, Seidl randomized controlled trial of resistance tional distress with diabetes treatment in K, Green AA, Talpers S. A low-fat vegan exercise training to improve glycemic primary care patients with Type 2 diabe- diet improves glycemic control and car- control in older adults with type 2 dia- tes. Diabet Med 2007;24:48 –54 diovascular risk factors in a randomized betes. Diabetes Care 2002;25:2335– 164. American Diabetes Association: Psycho- clinical trial in individuals with type 2 2341 social factors affecting adherence, qual- diabetes. Diabetes Care 2006;29:1777– 153. Sigal RJ, Kenny GP, Wasserman DH, ity of life, and well-being: Helping 1783 Castaneda-Sceppa C. Physical activity/ Patients cope. In Medical Management of144. Turner-McGrievy GM, Barnard ND, Co- exercise and type 2 diabetes. Diabetes Type 1 Diabetes. 5 ed. Francine R. Kauf- hen J, Jenkins DJ, Gloede L, Green AA. Care 2004;27:2518 –2539 man, Ed. Alexandria, VA, American Di- Changes in nutrient intake and dietary 154. Bax JJ, Young LH, Frye RL, Bonow RO, abetes Association, 2008, p. 173–193 quality among participants with type 2 Steinberg HO, Barrett EJ, ADA. Screen- 165. Anderson RJ, Freedland KE, Clouse RE, diabetes following a low-fat vegan diet ing for coronary artery disease in pa- Lustman PJ. The prevalence of comorbid or a conventional diabetes diet for 22 tients with diabetes. Diabetes Care 2007; depression in adults with diabetes: a weeks. J Am Diet Assoc 2008; 30:2729 –2736 meta-analysis. Diabetes Care 2001; 108:1636 –1645 155. Berger M, Berchtold P, Cuppers HJ, Drost ¨ 24:1069 –1078145. Franz MJ, Bantle JP, Beebe CA, Brunzell H, Kley HK, Muller WA, Wiegelmann W, ¨ 166. Fisher L, Skaff MM, Mullan JT, Arean JD, Chiasson JL, Garg A, Holzmeister Zimmerman-Telschow H, Gries FA, P, Mohr D, Masharani U, Glasgow R, LA, Hoogwerf B, Mayer-Davis E, Moora- Kruskemper HL, Zimmermann H. Meta- ¨ Laurencin G. Clinical depression ver- dian AD, Purnell JQ, Wheeler M. Evi- bolic and hormonal effects of muscular sus distress among patients with type 2 dence-based nutrition principles and exercise in juvenile type diabetics. Diabe- diabetes: not just a question of seman- recommendations for the treatment and tologia 1977;13:355–365 tics. Diabetes Care 2007;30:542–548 prevention of diabetes and related com- 156. Aiello LP, Wong J, Cavallerano J, Bursell 167. Gary TL, Safford MM, Gerzoff RB, Ettner plications. Diabetes Care 2002;25:148 – SE, Aiello LM: Retinopathy. In Handbook SL, Karter AJ, Beckles GL, Brown AF. 198 of Exercise in Diabetes. 2nd ed. Ruderman Perception of neighborhood problems,146. Boule NG, Haddad E, Kenny GP, Wells ´ N, Devlin JT, Kriska A, Eds. Alexandria, health behaviors, and diabetes outcomes GA, Sigal RJ. Effects of exercise on gly- VA, American Diabetes Association, among adults with diabetes in managed cemic control and body mass in type 2 2002, p. 401– 413 care: the Translating Research Into Ac- diabetes mellitus: a meta-analysis of 157. Lemaster JW, Reiber GE, Smith DG, tion for Diabetes (TRIAD) study. Diabe- controlled clinical trials. JAMA 2001; Heagerty PJ, Wallace C. Daily weight- tes Care 2008;31:273–278 286:1218 –1227 bearing activity does not increase the 168. Katon W, Fan MY, Unutzer J, Taylor J, ¨147. Boule NG, Kenny GP, Haddad E, Wells ´ risk of diabetic foot ulcers. Med Sci Pincus H, Schoenbaum M. Depression GA, Sigal RJ. Meta-analysis of the effect Sports Exerc 2003;35:1093–1099 and diabetes: a potentially lethal combi- of structured exercise training on cardio- 158. Vinik A, Erbas T: Neuropathy. In Hand- nation. J Gen Intern Med 2008;23: respiratory fitness in Type 2 diabetes book of Exercise in Diabetes. 2nd ed. Ru- 1571–1575 mellitus. Diabetologia 2003;46:1071– derman N, Devlin JT, Kriska A, Eds. 169. Zhang X, Norris SL, Gregg EW, Cheng 1081 Alexandria, VA, American Diabetes As- YJ, Beckles G, Kahn HS. Depressive148. Colberg SR, Sigal RJ, Fernhall B, Regen- sociation, 2002, p. 463– 496 symptoms and mortality among persons steiner JG, Blissmer BJ, Rubin RR, 159. Wackers FJ, Young LH, Inzucchi SE, with and without diabetes. Am J Epide- Chasen-Taber L, Albright AL, Braun B. Chyun DA, Davey JA, Barrett EJ, miol 2005;161:652– 660 Exercise and type 2 diabetes: the Amer- Taillefer R, Wittlin SD, Heller GV, Filip- 170. Rubin RR, Peyrot M. Psychological is- ican College of Sports Medicine and the chuk N, Engel S, Ratner RE, Iskandrian sues and treatments for people with di- American Diabetes Association: joint AE, Detection of Ischemia in Asymp- abetes. J Clin Psychol 2001;57:457– 478 position statement. Diabetes Care 2010; tomatic Diabetics Investigators. Detec- 171. Young-Hyman DL, Davis CL. Disor- 33:2692–2696 tion of silent myocardial ischemia in dered eating behavior in individuals149. U.S. Department of Health and Human asymptomatic diabetic subjects: the with diabetes: importance of context, Services: 2008 Physical Activity Guide- DIAD study. Diabetes Care 2004;27: evaluation, and classification. Diabetes lines for Americans. [article online], 1954 –1961 Care 2010;33:683– 689 2008. Available from http://www. 160. Valensi P, Sachs RN, Harfouche B, 172. Blonde L, Merilainen M, Karwe V, health.gov/paguidelines/guidelines/ Lormeau B, Paries J, Cosson E, Paycha F, Raskin P, TITRATE Study Group. Pa- default.aspx. Accessed December 2010. Leutenegger M, Attali JR. Predictive tient-directed titration for achieving gly-150. Cauza E, Hanusch-Enserer U, Strasser B, value of cardiac autonomic neuropathy caemic goals using a once-daily basal Ludvik B, Metz-Schimmerl S, Pacini G, in diabetic patients with or without si- insulin analogue: an assessment of two Wagner O, Georg P, Prager R, Kostner K, lent myocardial ischemia. Diabetes Care different fasting plasma glucose targets - Dunky A, Haber P. The relative benefits 2001;24:339 –343 the TITRATE study. Diabetes Obes of endurance and strength training on 161. Mogensen CE: Nephropathy. In Hand- Metab 2009;11:623– 631 the metabolic factors and muscle func- book of Exercise in Diabetes. 2nd ed. Ru- 173. Cryer PE. Hypoglycaemia: the limiting tion of people with type 2 diabetes mel- derman N, Devlin JT, Kriska A, Eds. factor in the glycaemic management ofcare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S53
    • Standards of Medical Care Type I and Type II diabetes. Diabetolo- Peeters A, Playfair J, O’Brien PE. Cost- Peto R, Collins R, Prospective Studies gia 2002;45:937–948 efficacy of surgically induced weight loss Collaboration. Age-specific relevance of174. Whitmer RA, Karter AJ, Yaffe K, Quesen- for the management of type 2 diabetes: a usual blood pressure to vascular mortal- berry CP, Jr, Selby JV. Hypoglycemic ep- randomized controlled trial. Diabetes ity: a meta-analysis of individual data for isodes and risk of dementia in older Care 2009;32:580 –584 one million adults in 61 prospective patients with type 2 diabetes mellitus. 185. Smith SA, Poland GA. Use of influenza studies. Lancet 2002;360:1903–1913 JAMA 2009;301:1565–1572 and pneumococcal vaccines in people 194. Stamler J, Vaccaro O, Neaton JD, Went-175. Diabetes Control and Complications with diabetes. Diabetes Care 2000;23: worth D. Diabetes, other risk factors, Trial/Epidemiology of Diabetes Inter- 95–108 and 12-yr cardiovascular mortality for ventions and Complications Study Re- 186. Colquhoun AJ, Nicholson KG, Botha JL, men screened in the Multiple Risk Fac- search Group, Jacobson AM, Musen G, Raymond NT. Effectiveness of influenza tor Intervention Trial. Diabetes Care Ryan CM, Silvers N, Cleary P, Waberski vaccine in reducing hospital admissions 1993;16:434 – 444 B, Burwood A, Weinger K, Bayless M, in people with diabetes. Epidemiol In- 195. UKPDS: Tight blood pressure control Dahms W, Harth J. Long-term effect of fect 1997;119:335–341 and risk of macrovascular and microvas- diabetes and its treatment on cognitive 187. Bridges CB, Fukuda K, Uyeki TM, Cox cular complications in type 2 diabetes: function. N Engl J Med 2007;356:1842– NJ, Singleton JA. Prevention and control UKPDS 38. UK Prospective Diabetes 1852 of influenza. Recommendations of the Study Group. BMJ 317:703–713, 1998176. Cryer PE. Diverse causes of hypoglyce- Advisory Committee on Immunization 196. Hansson L, Zanchetti A, Carruthers SG, mia-associated autonomic failure in dia- Practices (ACIP). MMWR Recomm Rep Dahlof B, Elmfeldt D, Julius S, Menard J, ¨ ´ betes. N Engl J Med 2004;350: 2002;51:1–31 Rahn KH, Wedel H, Westerling S. Ef- 2272–2279 188. Buse JB, Ginsberg HN, Bakris GL, Clark fects of intensive blood-pressure lower-177. Buchwald H, Estok R, Fahrbach K, Banel NG, Costa F, Eckel R, Fonseca V, Ger- ing and low-dose aspirin in patients with D, Jensen MD, Pories WJ, Bantle JP, stein HC, Grundy S, Nesto RW, Pignone hypertension: principal results of the Sledge I. Weight and type 2 diabetes af- MP, Plutzky J, Porte D, Redberg R, Stit- Hypertension Optimal Treatment (HOT) ter bariatric surgery: systematic review zel KF, Stone NJ, American Heart Asso- randomised trial. HOT Study Group. Lan- and meta-analysis. Am J Med 2009;122: ciation, American Diabetes Association. cet 1998;351:1755–1762 248 –256 Primary prevention of cardiovascular 197. Adler AI, Stratton IM, Neil HA, Yudkin178. Dixon JB, O’Brien PE, Playfair J, Chap- diseases in people with diabetes melli- JS, Matthews DR, Cull CA, Wright AD, man L, Schachter LM, Skinner S, Proi- tus: a scientific statement from the Turner RC, Holman RR. Association of etto J, Bailey M, Anderson M. Adjustable American Heart Association and the systolic blood pressure with macrovas- gastric banding and conventional ther- American Diabetes Association. Diabe- cular and microvascular complications apy for type 2 diabetes: a randomized tes Care 2007;30:162–172 of type 2 diabetes (UKPDS 36): prospec- controlled trial. JAMA 2008;299:316 – 189. Gaede P, Lund-Andersen H, Parving tive observational study. BMJ 2000;321: 323 HH, Pedersen O. Effect of a multifacto- 412– 419179. Hall TC, Pellen MG, Sedman PC, Jain rial intervention on mortality in type 2 198. ACCORD Study Group, Cushman WC, PK. Preoperative factors predicting re- diabetes. N Engl J Med 2008;358:580 – Evans GW, Byington RP, Goff DC Jr, mission of type 2 diabetes mellitus after 591 Grimm RH Jr, Cutler JA, Simons-Morton Roux-en-Y gastric bypass surgery for 190. Chobanian AV, Bakris GL, Black HR, DG, Basile JN, Corson MA, Probstfield obesity. Obes Surg 2010;20:1245–1250 Cushman WC, Green LA, Izzo JL Jr, JL, Katz L, Peterson KA, Friedewald WT,180. Buchwald H, Estok R, Fahrbach K, Banel Jones DW, Materson BJ, Oparil S, Buse JB, Bigger JT, Gerstein HC, Ismail- D, Sledge I. Trends in mortality in bari- Wright JT Jr, Roccella EJ, National Beigi F. Effects of intensive blood-pres- atric surgery: a systematic review and Heart, Lung, and Blood Institute Joint sure control in type 2 diabetes mellitus. meta-analysis. Surgery 2007;142:621– National Committee on Prevention, De- N Engl J Med 2010;362:1575–1585 632 tection, Evaluation, and Treatment of 199. Patel A, ADVANCE Collaborative181. Sjostrom L, Narbro K, Sjostrom CD, ¨ ¨ ¨ ¨ High Blood Pressure, National High Group, MacMahon S, Chalmers J, Neal Karason K, Larsson B, Wedel H, Lystig Blood Pressure Education Program Co- B, Woodward M, Billot L, Harrap S, T, Sullivan M, Bouchard C, Carlsson B, ordinating Committee. The Seventh Re- Poulter N, Marre M, Cooper M, Glasziou Bengtsson C, Dahlgren S, Gummesson port of the Joint National Committee on P, Grobbee DE, Hamet P, Heller S, Liu A, Jacobson P, Karlsson J, Lindroos AK, Prevention, Detection, Evaluation, and LS, Mancia G, Mogensen CE, Pan CY, Lonroth H, Naslund I, Olbers T, Stenlof ¨ ¨ ¨ Treatment of High Blood Pressure: the Rodgers A, Williams B. Effects of a fixed K, Torgerson J, Agren G, Carlsson LM, JNC 7 report. JAMA 2003;289:2560 – combination of perindopril and indap- Swedish Obese Subjects Study. Effects of 2572 amide on macrovascular and microvas- bariatric surgery on mortality in Swedish 191. Bobrie G, Genes N, Vaur L, Clerson P, ` cular outcomes in patients with type 2 obese subjects. N Engl J Med 2007;357: Vaisse B, Mallion JM, Chatellier G. Is diabetes mellitus (the ADVANCE trial): 741–752 ”isolated home“ hypertension as op- a randomised controlled trial. Lancet182. Hoerger TJ, Zhang P, Segel JE, Kahn HS, posed to ”isolated office“ hypertension a 2007;370:829 – 840 Barker LE, Couper S. Cost-effectiveness sign of greater cardiovascular risk? Arch 200. Cooper-DeHoff RM, Gong Y, Handberg of bariatric surgery for severely obese Intern Med 2001;161:2205–2211 EM, Bavry AA, Denardo SJ, Bakris GL, adults with diabetes. Diabetes Care 192. Sega R, Facchetti R, Bombelli M, Cesana Pepine CJ. Tight blood pressure control 2010;33:1933–1939 G, Corrao G, Grassi G, Mancia G. Prog- and cardiovascular outcomes among hy-183. Makary MA, Clarke JM, Shore AD, Mag- nostic value of ambulatory and home pertensive patients with diabetes and nuson TH, Richards T, Bass EB, Domi- blood pressures compared with office coronary artery disease. JAMA 2010; nici F, Weiner JP, Wu AW, Segal JB. blood pressure in the general popula- 304:61– 68 Medication utilization and annual health tion: follow-up results from the Pres- 201. Sacks FM, Svetkey LP, Vollmer WM, Ap- care costs in patients with type 2 diabe- sioni Arteriose Monitorate e Loro pel LJ, Bray GA, Harsha D, Obarzanek E, tes mellitus before and after bariatric Associazioni (PAMELA) study. Circula- Conlin PR, Miller ER 3rd, Simons-Mor- surgery. Arch Surg 2010;145:726 –731 tion 2005;111:1777–1783 ton DG, Karanja N, Lin PH, DASH-So-184. Keating CL, Dixon JB, Moodie ML, 193. Lewington S, Clarke R, Qizilbash N, dium Collaborative Research Group.S54 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement Effects on blood pressure of reduced di- and morbidity in patients with chronic wald E. Cardiovascular events and their etary sodium and the Dietary Ap- heart failure: the CHARM-Overall pro- reduction with pravastatin in diabetic proaches to Stop Hypertension (DASH) gramme. Lancet 2003;362:759 –766 and glucose-intolerant myocardial in- diet. DASH-Sodium Collaborative Re- 210. Granger CB, McMurray JJ, Yusuf S, Held farction survivors with average choles- search Group. N Engl J Med 2001;344: P, Michelson EL, Olofsson B, Ostergren terol levels: subgroup analyses in the 3–10 J, Pfeffer MA, Swedberg K, CHARM In- cholesterol and recurrent events (CARE)202. Tatti P, Pahor M, Byington RP, Di Mauro vestigators and Committees. Effects of trial. The Care Investigators. Circulation P, Guarisco R, Strollo G, Strollo F. Out- candesartan in patients with chronic 1998;98:2513–2519 come results of the Fosinopril Versus heart failure and reduced left-ventricular 218. Shepherd J, Barter P, Carmena R, Deed- Amlodipine Cardiovascular Events Ran- systolic function intolerant to angioten- wania P, Fruchart JC, Haffner S, Hsia J, domized Trial (FACET) in patients with sin-converting-enzyme inhibitors: the Breazna A, LaRosa J, Grundy S, Waters hypertension and NIDDM. Diabetes CHARM-Alternative trial. Lancet 2003; D. Effect of lowering LDL cholesterol Care 1998;21:597– 603 362:772–776 substantially below currently recom-203. Estacio RO, Jeffers BW, Hiatt WR, Big- 211. Lindholm LH, Ibsen H, Dahlof B, De- ¨ mended levels in patients with coronary gerstaff SL, Gifford N, Schrier RW. The vereux RB, Beevers G, de Faire U, Fyhr- heart disease and diabetes: the Treating effect of nisoldipine as compared with quist F, Julius S, Kjeldsen SE, to New Targets (TNT) study. Diabetes enalapril on cardiovascular outcomes in Kristiansson K, Lederballe-Pedersen O, Care 2006;29:1220 –1226 patients with non-insulin-dependent di- Nieminen MS, Omvik P, Oparil S, 219. Sever PS, Poulter NR, Dahlof B, Wedel ¨ abetes and hypertension. N Engl J Med Wedel H, Aurup P, Edelman J, Snapinn H, Collins R, Beevers G, Caulfield M, 1998;338:645– 652 S, LIFE Study Group. Cardiovascular Kjeldsen SE, Kristinsson A, McInnes GT,204. Schrier RW, Estacio RO, Mehler PS, Hi- morbidity and mortality in patients with Mehlsen J, Nieminen M, O’Brien E, Os- att WR. Appropriate blood pressure diabetes in the Losartan Intervention For tergren J. Reduction in cardiovascular control in hypertensive and normoten- Endpoint reduction in hypertension events with atorvastatin in 2,532 pa- sive type 2 diabetes mellitus: a summary study (LIFE): a randomised trial against tients with type 2 diabetes: Anglo-Scan- of the ABCD trial. Nat Clin Pract Neph- atenolol. Lancet 2002;359:1004 –1010 dinavian Cardiac Outcomes Trial–lipid- rol 2007;3:428 – 438 212. Berl T, Hunsicker LG, Lewis JB, Pfeffer lowering arm (ASCOT-LLA). Diabetes205. ALLHAT Officers and Coordinators for MA, Porush JG, Rouleau JL, Drury PL, Care 2005;28:1151–1157 the ALLHAT Collaborative Research Esmatjes E, Hricik D, Parikh CR, Raz I, 220. Knopp RH, d’Emden M, Smilde JG, Pocock Group. The Antihypertensive and Lipid- Vanhille P, Wiegmann TB, Wolfe BM, SJ. Efficacy and safety of atorvastatin in the Lowering Treatment to Prevent Heart Locatelli F, Goldhaber SZ, Lewis EJ, prevention of cardiovascular end points in Attack Trial. The Antihypertensive and Irbesartan Diabetic Nephropathy Trial. subjects with type 2 diabetes: the Atorvasta- Lipid-Lowering Treatment to Prevent Collaborative Study Group. Collabora- tin Study for Prevention of Coronary Heart Heart Attack Trial: Major outcomes in tive Study Group. Cardiovascular out- Disease Endpoints in non-insulin-depen- high-risk hypertensive patients random- comes in the Irbesartan Diabetic dent diabetes mellitus (ASPEN). Diabetes ized to angiotensin-converting enzyme Nephropathy Trial of patients with type Care 2006;29:1478–1485 inhibitor or calcium channel blocker vs 2 diabetes and overt nephropathy. Ann 221. Colhoun HM, Betteridge DJ, Durrington diuretic: The Antihypertensive and Lip- Intern Med 2003;138:542–549 PN, Hitman GA, Neil HA, Livingstone SJ, id-Lowering Treatment to Prevent Heart 213. Sibai BM. Treatment of hypertension in Thomason MJ, Mackness MI, Charlton- Attack Trial (ALLHAT). JAMA 288: pregnant women. N Engl J Med 1996; Menys V, Fuller JH, CARDS investigators. 2981–2997, 2002 335:257–265 Primary prevention of cardiovascular dis-206. Psaty BM, Smith NL, Siscovick DS, Ko- 214. Baigent C, Keech A, Kearney PM, Black- ease with atorvastatin in type 2 diabetes in epsell TD, Weiss NS, Heckbert SR, Le- well L, Buck G, Pollicino C, Kirby A, the Collaborative Atorvastatin Diabetes maitre RN, Wagner EH, Furberg CD. Sourjina T, Peto R, Collins R, Simes R, Study (CARDS): multicentre randomised Health outcomes associated with antihy- Cholesterol Treatment Trialists’ (CTT) placebo-controlled trial. Lancet 2004;364: pertensive therapies used as first-line Collaborators. Efficacy and safety of 685– 696 agents. A systematic review and meta- cholesterol-lowering treatment: pro- 222. Singh IM, Shishehbor MH, Ansell BJ. analysis. JAMA 1997;277:739 –745 spective meta-analysis of data from High-density lipoprotein as a therapeu-207. HOPE: Effects of ramipril on cardiovas- 90,056 participants in 14 randomised tic target: a systematic review. JAMA cular and microvascular outcomes in trials of statins. Lancet 2005;366:1267– 2007;298:786 –798 people with diabetes mellitus: results of 1278 223. Canner PL, Berge KG, Wenger NK, the HOPE study and MICRO-HOPE 215. Pyorala K, Pedersen TR, Kjekshus J, ˘ ¨ ¨ Stamler J, Friedman L, Prineas RJ, substudy. Heart Outcomes Prevention Faergeman O, Olsson AG, Thorgeirsson Friedewald W. Fifteen year mortality in Evaluation Study Investigators. Lancet G. Cholesterol lowering with simvasta- Coronary Drug Project patients: long- 355:253–259, 2000 tin improves prognosis of diabetic pa- term benefit with niacin. J Am Coll Car-208. McMurray JJ, Ostergren J, Swedberg K, tients with coronary heart disease: a diol 1986;8:1245–1255 Granger CB, Held P, Michelson EL, Olofs- subgroup analysis of the Scandinavian 224. Rubins HB, Robins SJ, Collins D, Fye CL, son B, Yusuf S, Pfeffer MA, CHARM Inves- Simvastatin Survival Study (4S). Diabe- Anderson JW, Elam MB, Faas FH, Lin- tigators and Committees. Effects of tes Care 1997;20:614 – 620 ares E, Schaefer EJ, Schectman G, Wilt candesartan in patients with chronic heart 216. Collins R, Armitage J, Parish S, Sleigh P, TJ, Wittes J. Gemfibrozil for the second- failure and reduced left-ventricular sys- Peto R, Heart Protection Study Collabo- ary prevention of coronary heart disease tolic function taking angiotensin-convert- rative Group: MRC/BHF Heart Protec- in men with low levels of high-density ing-enzyme inhibitors: the CHARM- tion Study of cholesterol-lowering with lipoprotein cholesterol. Veterans Affairs Added trial. Lancet 2003;362:767–771 simvastatin in 5963 people with diabe- High-Density Lipoprotein Cholesterol209. Pfeffer MA, Swedberg K, Granger CB, tes: a randomised placebo-controlled Intervention Trial Study Group. N Engl Held P, McMurray JJ, Michelson EL, trial. Lancet 361:2005–2016, 2003 J Med 1999;341:410 – 418 Olofsson B, Ostergren J, Yusuf S, Pocock 217. Goldberg RB, Mellies MJ, Sacks FM, 225. Frick MH, Elo O, Haapa K, Heinonen S, CHARM Investigators and Commit- Moye LA, Howard BV, Howard WJ, ´ OP, Heinsalmi P, Helo P, Huttunen JK, tees. Effects of candesartan on mortality Davis BR, Cole TG, Pfeffer MA, Braun- Kaitaniemi P, Koskinen P, Manninen V.care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S55
    • Standards of Medical Care Helsinki Heart Study: primary-preven- Program Adult Treatment Panel III patients with type 2 diabetes: a random- tion trial with gemfibrozil in middle- guidelines. Circulation 2004;110:227– ized controlled trial. JAMA 2008;300: aged men with dyslipidemia. Safety of 239 2134 –2141 treatment, changes in risk factors, and 233. Chasman DI, Posada D, Subrahmanyan 241. Belch J, MacCuish A, Campbell I, Cobbe incidence of coronary heart disease. L, Cook NR, Stanton VP, Jr, Ridker PM. S, Taylor R, Prescott R, Lee R, Bancroft J, N Engl J Med 1987;317:1237–1245 Pharmacogenetic study of statin therapy MacEwan S, Shepherd J, Macfarlane P,226. Keech A, Simes RJ, Barter P, Best J, Scott and cholesterol reduction. JAMA 2004; Morris A, Jung R, Kelly C, Connacher A, R, Taskinen MR, Forder P, Pillai A, Davis 291:2821–2827 Peden N, Jamieson A, Matthews D, Leese T, Glasziou P, Drury P, Kesaniemi YA, ¨ 234. Brunzell JD, Davidson M, Furberg CD, G, McKnight J, O’Brien I, Semple C, Pet- Sullivan D, Hunt D, Colman P, d’Emden Goldberg RB, Howard BV, Stein JH, Wit- rie J, Gordon D, Pringle S, MacWalter R. M, Whiting M, Ehnholm C, Laakso M, ztum JL, American Diabetes Association, The prevention of progression of arterial FIELD study investigators. Effects of American College of Cardiology Foun- disease and diabetes (POPADAD) trial: long-term fenofibrate therapy on cardio- dation. Lipoprotein management in factorial randomised placebo controlled vascular events in 9795 people with type patients with cardiometabolic risk: con- trial of aspirin and antioxidants in pa- 2 diabetes mellitus (the FIELD study): sensus statement from the American Di- tients with diabetes and asymptomatic randomised controlled trial. Lancet abetes Association and the American peripheral arterial disease. BMJ 2008; 2005;366:1849 –1861 College of Cardiology Foundation. Dia- 337:a1840227. Expert Panel on Detection, Evaluation, betes Care 2008;31:811– 822 242. Pignone M, Earnshaw S, Tice JA, and Treatment of High Blood Choles- 235. Elam MB, Hunninghake DB, Davis KB, Pletcher MJ. Aspirin, statins, or both terol in Adults: Executive Summary of Garg R, Johnson C, Egan D, Kostis JB, drugs for the primary prevention of cor- The Third Report of The National Cho- Sheps DS, Brinton EA. Effect of niacin on onary heart disease events in men: a lesterol Education Program (NCEP) Ex- lipid and lipoprotein levels and glycemic cost-utility analysis. Ann Intern Med pert Panel on Detection, Evaluation, control in patients with diabetes and pe- 2006;144:326 –336 And Treatment of High Blood Choles- ripheral arterial disease: the ADMIT 243. Pignone M, Alberts MJ, Colwell JA, terol In Adults (Adult Treatment Panel study: A randomized trial. Arterial Dis- Cushman M, Inzucchi SE, Mukherjee D, III). JAMA 2001;285:2486 –2497 ease Multiple Intervention Trial. JAMA Rosenson RS, Williams CD, Wilson PW,228. Hayward RA, Hofer TP, Vijan S. Narrative 2000;284:1263–1270 Kirkman MS, American Diabetes Associ- review: lack of evidence for recommended 236. Grundy SM, Vega GL, McGovern ME, ation, American Heart Association, low-density lipoprotein treatment targets: Tulloch BR, Kendall DM, Fitz-Patrick D, American College of Cardiology Foun- a solvable problem. Ann Intern Med 2006; Ganda OP, Rosenson RS, Buse JB, Rob- dation. Aspirin for primary prevention 145:520 –530 ertson DD, Sheehan JP, Diabetes Multi- of cardiovascular events in people with229. Cannon CP, Braunwald E, McCabe CH, center Research Group. Efficacy, safety, diabetes: a position statement of the Rader DJ, Rouleau JL, Belder R, Joyal SV, and tolerability of once-daily niacin for American Diabetes Association, a scien- Hill KA, Pfeffer MA, Skene AM, Prava- the treatment of dyslipidemia associated tific statement of the American Heart As- statin or Atorvastatin Evaluation and with type 2 diabetes: results of the as- sociation, and an expert consensus Infection Therapy-Thrombolysis in sessment of diabetes control and evalu- document of the American College of Myocardial Infarction 22 Investigators. ation of the efficacy of niaspan trial. Arch Cardiology Foundation. Diabetes Care Intensive versus moderate lipid lowering Intern Med 2002;162:1568 –1576 2010;33:1395–1402 with statins after acute coronary syn- 237. Jones PH, Davidson MH. Reporting rate 244. Campbell CL, Smyth S, Montalescot G, dromes. N Engl J Med 2004;350:1495– of rhabdomyolysis with fenofibrate Steinhubl SR. Aspirin dose for the pre- 1504 statin versus gemfibrozil any statin. vention of cardiovascular disease: a sys-230. de Lemos JA, Blazing MA, Wiviott SD, Am J Cardiol 2005;95:120 –122 tematic review. JAMA 2007;297:2018 – Lewis EF, Fox KA, White HD, Rouleau 238. ACCORD Study Group, Ginsberg HN, 2024 JL, Pedersen TR, Gardner LH, Mukher- Elam MB, Lovato LC, Crouse JR 3rd, Le- 245. Davì G, Patrono C. Platelet activation jee R, Ramsey KE, Palmisano J, Bilhei- iter LA, Linz P, Friedewald WT, Buse JB, and atherothrombosis. N Engl J Med mer DW, Pfeffer MA, Califf RM, Gerstein HC, Probstfield J, Grimm RH, 2007;357:2482–2494 Braunwald E, A to Z Investigators. Early Ismail-Beigi F, Bigger JT, Goff DC Jr, 246. Bhatt DL, Marso SP, Hirsch AT, Ringleb intensive vs a delayed conservative sim- Cushman WC, Simons-Morton DG, By- PA, Hacke W, Topol EJ. Amplified ben- vastatin strategy in patients with acute ington RP. Effects of combination lipid efit of clopidogrel versus aspirin in pa- coronary syndromes: phase Z of the A to therapy in type 2 diabetes mellitus. tients with diabetes mellitus. Am J Z trial. JAMA 2004;292:1307–1316 N Engl J Med 2010;362:1563–1574 Cardiol 2002;90:625– 628231. Nissen SE, Tuzcu EM, Schoenhagen P, 239. Antithrombotic Trialists’ (ATT) Collab- 247. Ranney L, Melvin C, Lux L, McClain E, Brown BG, Ganz P, Vogel RA, Crowe T, oration, Baigent C, Blackwell L, Collins Lohr KN. Systematic review: smoking Howard G, Cooper CJ, Brodie B, Grines R, Emberson J, Godwin J, Peto R, Buring cessation intervention strategies for CL, DeMaria AN, REVERSAL Investiga- J, Hennekens C, Kearney P, Meade T, adults and adults in special populations. tors. Effect of intensive compared with Patrono C, Roncaglioni MC, Zanchetti Ann Intern Med 2006;145:845– 856 moderate lipid-lowering therapy on pro- A. Aspirin in the primary and secondary 248. Scognamiglio R, Negut C, Ramondo A, gression of coronary atherosclerosis: a prevention of vascular disease: collabo- Tiengo A, Avogaro A. Detection of coro- randomized controlled trial. JAMA rative meta-analysis of individual partic- nary artery disease in asymptomatic pa- 2004;291:1071–1080 ipant data from randomised trials. tients with type 2 diabetes mellitus. J Am232. Grundy SM, Cleeman JI, Merz CN, Lancet 2009;373:1849 –1860 Coll Cardiol 2006;47:65–71 Brewer HB Jr, Clark LT, Hunninghake 240. Ogawa H, Nakayama M, Morimoto T, 249. Boden WE, O’Rourke RA, Teo KK, Har- DB, Pasternak RC, Smith SC Jr, Stone Uemura S, Kanauchi M, Doi N, Jinnou- tigan PM, Maron DJ, Kostuk WJ, Knudt- NJ, National Heart, Lung, and Blood In- chi H, Sugiyama S, Saito Y, Japanese Pri- son M, Dada M, Casperson P, Harris CL, stitute, American College of Cardiology mary Prevention of Atherosclerosis With Chaitman BR, Shaw L, Gosselin G, Foundation, American Heart Associa- Aspirin for Diabetes (JPAD) Trial Inves- Nawaz S, Title LM, Gau G, Blaustein AS, tion. Implications of recent clinical trials tigators. Low-dose aspirin for primary Booth DC, Bates ER, Spertus JA, Berman for the National Cholesterol Education prevention of atherosclerotic events in DS, Mancini GB, Weintraub WS,S56 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement COURAGE Trial Research Group. Opti- Investigators, Yusuf S, Teo K, Anderson Hypertension and Diabetes Executive mal medical therapy with or without PCI C, Pogue J, Dyal L, Copland I, Schu- Committees Working Group. Am J Kid- for stable coronary disease. N Engl J Med macher H, Dagenais G, Sleight P. Effects ney Dis 2000;36:646 – 661 2007;356:1503–1516 of the angiotensin-receptor blocker 267. Remuzzi G, Macia M, Ruggenenti P. Pre-250. BARI 2D Study Group, Frye RL, August telmisartan on cardiovascular events in vention and treatment of diabetic renal P, Brooks MM, Hardison RM, Kelsey SF, high-risk patients intolerant to angioten- disease in type 2 diabetes: the BENE- MacGregor JM, Orchard TJ, Chaitman sin-converting enzyme inhibitors: a ran- DICT study. J Am Soc Nephrol 2006;17: BR, Genuth SM, Goldberg SH, Hlatky domised controlled trial. Lancet 2008; S90 –S97 MA, Jones TL, Molitch ME, Nesto RW, 372:1174 –1183 268. Bilous R, Chaturvedi N, Sjølie AK, Fuller Sako EY, Sobel BE. A randomized trial of 258. Garg JP, Bakris GL. Microalbuminuria: J, Klein R, Orchard T, Porta M, Parving therapies for type 2 diabetes and coro- marker of vascular dysfunction, risk fac- HH. Effect of candesartan on microalbu- nary artery disease. N Engl J Med 2009; tor for cardiovascular disease. Vasc Med minuria and albumin excretion rate in 360:2503–2515 2002;7:35– 43 diabetes: three randomized trials. Ann251. Wackers FJ, Chyun DA, Young LH, 259. Klausen K, Borch-Johnsen K, Feldt-Ras- Intern Med 2009;151:11–14 Heller GV, Iskandrian AE, Davey JA, mussen B, Jensen G, Clausen P, 269. Mauer M, Zinman B, Gardiner R, Suissa Barrett EJ, Taillefer R, Wittlin SD, Filip- Scharling H, Appleyard M, Jensen JS. S, Sinaiko A, Strand T, Drummond K, chuk N, Ratner RE, Inzucchi SE, Detec- Very low levels of microalbuminuria are Donnelly S, Goodyer P, Gubler MC, tion of Ischemia in Asymptomatic associated with increased risk of coro- Klein R. Renal and retinal effects of ena- Diabetics (DIAD) Investigators. Resolu- nary heart disease and death indepen- lapril and losartan in type 1 diabetes. tion of asymptomatic myocardial isch- dently of renal function, hypertension, N Engl J Med 2009;361:40 –51 emia in patients with type 2 diabetes in and diabetes. Circulation 2004;110: 270. Lewis EJ, Hunsicker LG, Clarke WR, the Detection of Ischemia in Asymptom- 32–35 Berl T, Pohl MA, Lewis JB, Ritz E, Atkins atic Diabetics (DIAD) study. Diabetes 260. Gall MA, Hougaard P, Borch-Johnsen K, RC, Rohde R, Raz I, Collaborative Study Care 2007;30:2892–2898 Parving HH. Risk factors for develop- Group. Renoprotective effect of the an-252. Young LH, Wackers FJ, Chyun DA, Davey ment of incipient and overt diabetic ne- giotensin-receptor antagonist irbesartan JA, Barrett EJ, Taillefer R, Heller GV, Iskan- phropathy in patients with non-insulin in patients with nephropathy due to type drian AE, Wittlin SD, Filipchuk N, Ratner dependent diabetes mellitus: prospec- 2 diabetes. N Engl J Med 2001;345:851– RE, Inzucchi SE, DIAD Investigators. Car- tive, observational study. BMJ 1997; 860 diac outcomes after screening for asymp- 314:783–788 271. Brenner BM, Cooper ME, de Zeeuw D, tomatic coronary artery disease in patients 261. Ravid M, Lang R, Rachmani R, Lishner Keane WF, Mitch WE, Parving HH, Re- with type 2 diabetes: the DIAD study: a M. Long-term renoprotective effect of muzzi G, Snapinn SM, Zhang Z, Shahin- randomized controlled trial. JAMA 2009; angiotensin-converting enzyme inhibi- far S, RENAAL Study Investigators. 301:1547–1555 tion in non-insulin-dependent diabetes Effects of losartan on renal and cardio-253. Hadamitzky M, Hein F, Meyer T, mellitus. A 7-year follow-up study. Arch vascular outcomes in patients with type Bischoff B, Martinoff S, Schomig A, ¨ Intern Med 1996;156:286 –289 2 diabetes and nephropathy. N Engl Hausleiter J. Prognostic value of coro- 262. Reichard P, Nilsson BY, Rosenqvist U. J Med 2001;345:861– 869 nary computed tomographic angiogra- The effect of long-term intensified insu- 272. Parving HH, Lehnert H, Brochner- ¨ phy in diabetic patients without known lin treatment on the development of mi- Mortensen J, Gomis R, Andersen S, coronary artery disease. Diabetes Care crovascular complications of diabetes Arner P, Irbesartan in Patients with Type 2010;33:1358 –1363 mellitus. N Engl J Med 1993;329:304 – 2 Diabetes and Microalbuminuria Study254. Elkeles RS, Godsland IF, Feher MD, 309 Group. The effect of irbesartan on the Rubens MB, Roughton M, Nugara F, 263. DCCT: Effect of intensive therapy on the development of diabetic nephropathy in Humphries SE, Richmond W, Flather development and progression of dia- patients with type 2 diabetes. N Engl MD, PREDICT Study Group. Coronary betic nephropathy in the Diabetes Con- J Med 2001;345:870 – 878 calcium measurement improves predic- trol and Complications Trial. The 273. Pepine CJ, Handberg EM, Cooper-De- tion of cardiovascular events in asymp- Diabetes Control and Complications Hoff RM, Marks RG, Kowey P, Messerli tomatic patients with type 2 diabetes: (DCCT) Research Group. Kidney Int 47: FH, Mancia G, Cangiano JL, Garcia-Bar- the PREDICT study. Eur Heart J 2008; 1703–1720, 1995 reto D, Keltai M, Erdine S, Bristol HA, 29:2244 –2251 264. Lewis EJ, Hunsicker LG, Bain RP, Rohde Kolb HR, Bakris GL, Cohen JD, Parmley255. Choi EK, Chun EJ, Choi SI, Chang RD. The effect of angiotensin-convert- WW, INVEST Investigators. A calcium SA, Choi SH, Lim S, Rivera JJ, Nasir K, ing-enzyme inhibition on diabetic ne- antagonist vs a non-calcium antagonist Blumenthal RS, Jang HC, Chang HJ. phropathy. The Collaborative Study hypertension treatment strategy for pa- Assessment of subclinical coronary ath- Group. N Engl J Med 1993;329:1456 – tients with coronary artery disease: the erosclerosis in asymptomatic patients with 1462 International Verapamil-Trandolapril type 2 diabetes mellitus with single pho- 265. Laffel LM, McGill JB, Gans DJ. The ben- study (INVEST): a randomized con- ton emission computed tomography and eficial effect of angiotensin-converting trolled trial. JAMA 2003;290:2805– coronary computed tomography angiog- enzyme inhibition with captopril on di- 2816 raphy. Am J Cardiol 2009;104:890 – 896 abetic nephropathy in normotensive 274. Bakris GL, Siomos M, Richardson D,256. Braunwald E, Domanski MJ, Fowler SE, IDDM patients with microalbuminuria. Janssen I, Bolton WK, Hebert L, Agar- Geller NL, Gersh BJ, Hsia J, Pfeffer MA, North American Microalbuminuria wal R, Catanzaro D. ACE inhibition or Rice MM, Rosenberg YD, Rouleau JL, Study Group. Am J Med 1995;99:497– angiotensin receptor blockade: impact PEACE Trial Investigators. Angiotensin- 504 on potassium in renal failure. VAL-K converting-enzyme inhibition in stable 266. Bakris GL, Williams M, Dworkin L, El- Study Group. Kidney Int 2000;58: coronary artery disease. N Engl J Med liott WJ, Epstein M, Toto R, Tuttle K, 2084 –2092 2004;351:2058 –2068 Douglas J, Hsueh W, Sowers J. Preserv- 275. Mogensen CE, Neldam S, Tikkanen I,257. Telmisartan Randomised AssessmeNt ing renal function in adults with hyper- Oren S, Viskoper R, Watts RW, Cooper Study in ACE iNtolerant subjects with tension and diabetes: a consensus ME. Randomised controlled trial of dual cardiovascular Disease (TRANSCEND) approach. National Kidney Foundation blockade of renin-angiotensin system incare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S57
    • Standards of Medical Care patients with hypertension, microalbu- 287. Levey AS, Bosch JP, Lewis JB, Greene T, 301. Boulton AJ, Vinik AI, Arezzo JC, Bril V, minuria, and non-insulin dependent di- Rogers N, Roth D. A more accurate Feldman EL, Freeman R, Malik RA, Ma- abetes: the candesartan and lisinopril method to estimate glomerular filtration ser RE, Sosenko JM, Ziegler D, American microalbuminuria (CALM) study. BMJ rate from serum creatinine: a new pre- Diabetes Association. Diabetic neuropa- 2000;321:1440 –1444 diction equation. Modification of Diet in thies: a statement by the American Dia-276. Schjoedt KJ, Jacobsen P, Rossing K, Renal Disease Study Group. Ann Intern betes Association. Diabetes Care 2005; Boomsma F, Parving HH. Dual blockade Med 1999;130:461– 470 28:956 –962 of the renin-angiotensin-aldosterone 288. Rigalleau V, Lasseur C, Perlemoine C, 302. Wile DJ, Toth C. Association of met- system in diabetic nephropathy: the role Barthe N, Raffaitin C, Liu C, Chauveau formin, elevated homocysteine, and of aldosterone. Horm Metab Res 2005; P, Baillet-Blanco L, Beauvieux MC, methylmalonic acid levels and clinically 37(Suppl. 1):4 – 8 Combe C, Gin H. Estimation of glomer- worsened diabetic peripheral neuropa-277. Schjoedt KJ, Rossing K, Juhl TR, ular filtration rate in diabetic subjects: thy. Diabetes Care 2010;33:156 –161 Boomsma F, Rossing P, Tarnow L, Parv- Cockcroft formula or modification of 303. Freeman R. Not all neuropathy in diabe- ing HH. Beneficial impact of spironolac- Diet in Renal Disease study equation? tes is of diabetic etiology: differential di- tone in diabetic nephropathy. Kidney Diabetes Care 2005;28:838 – 843 agnosis of diabetic neuropathy. Curr Int 2005;68:2829 –2836 289. Levinsky NG. Specialist evaluation in Diab Rep 2009;9:423– 431278. Parving HH, Persson F, Lewis JB, Lewis chronic kidney disease: too little, too late. 304. Vinik AI, Maser RE, Mitchell BD, Free- EJ, Hollenberg NK, AVOID Study Inves- Ann Intern Med 2002;137:542–543 man R. Diabetic autonomic neuropathy. tigators. Aliskiren combined with losar- 290. Klein R. Hyperglycemia and microvas- Diabetes Care 2003;26:1553–1579 tan in type 2 diabetes and nephropathy. cular and macrovascular disease in dia- 305. Boulton AJ, Armstrong DG, Albert SF, N Engl J Med 2008;358:2433–2446 betes. Diabetes Care 1995;18:258 –268 Frykberg RG, Hellman R, Kirkman MS,279. Pijls LT, de Vries H, Donker AJ, van Eijk 291. Estacio RO, McFarling E, Biggerstaff S, Lavery LA, Lemaster JW, Mills JL Sr, JT. The effect of protein restriction on Jeffers BW, Johnson D, Schrier RW. Mueller MJ, Sheehan P, Wukich DK, albuminuria in patients with type 2 dia- Overt albuminuria predicts diabetic ret- American Diabetes Association, Ameri- betes mellitus: a randomized trial. inopathy in Hispanics with NIDDM. can Association of Clinical Endocrinolo- Nephrol Dial Transplant 1999;14: Am J Kidney Dis 1998;31:947–953 gists. Comprehensive foot examination 1445–1453 292. Leske MC, Wu SY, Hennis A, Hyman L, and risk assessment: a report of the task280. Pedrini MT, Levey AS, Lau J, Chalmers Nemesure B, Yang L, Schachat AP, Bar- force of the foot care interest group of TC, Wang PH. The effect of dietary pro- bados Eye Study Group. Hyperglycemia, the American Diabetes Association, with tein restriction on the progression of di- blood pressure, and the 9-year incidence endorsement by the American Associa- abetic and nondiabetic renal diseases: a of diabetic retinopathy: the Barbados tion of Clinical Endocrinologists. Diabe- meta-analysis. Ann Intern Med 1996; Eye Studies. Ophthalmology 2005;112: tes Care 2008;31:1679 –1685 124:627– 632 799 – 805 306. American Diabetes Association: Periph-281. Hansen HP, Tauber-Lassen E, Jensen 293. Fong DS, Aiello LP, Ferris FL 3rd, Klein eral arterial disease in people with dia- BR, Parving HH. Effect of dietary protein R. Diabetic retinopathy. Diabetes Care betes (Consensus Statement). Diabetes restriction on prognosis in patients with 2004;27:2540 –2553 Care 2003;26:3333–3341 diabetic nephropathy. Kidney Int 2002; 294. Diabetes Control and Complications 307. Silverstein J, Klingensmith G, Copeland 62:220 –228 Trial Research Group: Effect of preg- KC, Plotnick L, Kaufman F, Laffel L,282. Kasiske BL, Lakatua JD, Ma JZ, Louis TA. nancy on microvascular complications Deeb LC, Grey M, Anderson BJ, Hol- A meta-analysis of the effects of dietary in the diabetes control and complica- zmeister LA, Clark NG. Care of children protein restriction on the rate of decline tions trial. The Diabetes Control and and adolescents with type 1 diabetes in renal function. Am J Kidney Dis 1998; Complications Trial Research Group. mellitus: a statement of the American Di- 31:954 –961 Diabetes Care 2000;23:1084 –1091 abetes Association. Diabetes Care 2005;283. Eknoyan G, Hostetter T, Bakris GL, He- 295. Preliminary report on effects of photoco- 28:186 –212 bert L, Levey AS, Parving HH, Steffes agulation therapy. The Diabetic Reti- 308. Northam EA, Anderson PJ, Werther GA, MW, Toto R. Proteinuria and other nopathy Study Research Group. Am J Warne GL, Adler RG, Andrewes D. Neu- markers of chronic kidney disease: a po- Ophthalmol 1076;81:383–396 ropsychological complications of IDDM sition statement of the national kidney 296. ETDRS: Photocoagulation for diabetic in children 2 years after disease onset. foundation (NKF) and the national insti- macular edema. Early Treatment Dia- Diabetes Care 1998;21:379 –384 tute of diabetes and digestive and kidney betic Retinopathy Study report number 309. Rovet J, Alvarez M. Attentional function- diseases (NIDDK). Am J Kidney Dis 1. Early Treatment Diabetic Retinopathy ing in children and adolescents with 2003;42:617– 622 Study research group. Arch Ophthalmol IDDM. Diabetes Care 1997;20:803–284. Levey AS, Coresh J, Balk E, Kausz AT, 1985;103:1796 –1806 810 Levin A, Steffes MW, Hogg RJ, Perrone 297. American Diabetes Association: Reti- 310. Bjørgaas M, Gimse R, Vik T, Sand T. RD, Lau J, Eknoyan G, National Kidney nopathy in diabetes (Position State- Cognitive function in type 1 diabetic Foundation. National Kidney Founda- ment). Diabetes Care 2004;27(Suppl. children with and without episodes of tion practice guidelines for chronic kid- 1):S84 –S87 severe hypoglycaemia. Acta Paediatr ney disease: evaluation, classification, 298. Ahmed J, Ward TP, Bursell SE, Aiello 1997;86:148 –153 and stratification. Ann Intern Med 2003; LM, Cavallerano JD, Vigersky RA. The 311. Nimri R, Weintrob N, Benzaquen H, 139:137–147 sensitivity and specificity of nonmydri- Ofan R, Fayman G, Phillip M. Insulin285. Kramer H, Molitch ME. Screening for atic digital stereoscopic retinal imaging pump therapy in youth with type 1 dia- kidney disease in adults with diabetes. in detecting diabetic retinopathy. Diabe- betes: a retrospective paired study. Pedi- Diabetes Care 2005;28:1813–1816 tes Care 2006;29:2205–2209 atrics 2006;117:2126 –2131286. Kramer HJ, Nguyen QD, Curhan G, Hsu 300. Ciulla TA, Amador AG, Zinman B. Dia- 312. Doyle EA, Weinzimer SA, Steffen AT, CY. Renal insufficiency in the absence of betic retinopathy and diabetic macular Ahern JA, Vincent M, Tamborlane WV. albuminuria and retinopathy among edema: pathophysiology, screening, and A randomized, prospective trial compar- adults with type 2 diabetes mellitus. novel therapies. Diabetes Care 2003;26: ing the efficacy of continuous subcuta- JAMA 2003;289:3273–3277 2653–2664 neous insulin infusion with multipleS58 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement daily injections using insulin glargine. Metabolism, High Blood Pressure Re- ciated with type 1 diabetes mellitus. En- Diabetes Care 2004;27:1554 –1558 search, Cardiovascular Nursing, and the docrinol Metab Clin North Am 2004;33:313. Perantie DC, Wu J, Koller JM, Lim A, Kidney in Heart Disease; and the Inter- 197–214, xi Warren SL, Black KJ, Sadler M, White disciplinary Working Group on Quality 328. Roldan MB, Alonso M, Barrio R. Thyroid ´ NH, Hershey T. Regional brain volume of Care and Outcomes Research: en- autoimmunity in children and adoles- differences associated with hyperglyce- dorsed by the American Academy of Pe- cents with Type 1 diabetes mellitus. Di- mia and severe hypoglycemia in youth diatrics. Circulation 2006;114:2710 – abetes Nutr Metab 1999;12:27–31 with type 1 diabetes. Diabetes Care 2738 329. Kordonouri O, Deiss D, Danne T, 2007;30:2331–2337 320. McCrindle BW, Urbina EM, Dennison Dorow A, Bassir C, Gruters-Kieslich A. ¨314. Makimattila S, Malmberg-Ceder K, Hak- ¨ ` ¨ BA, Jacobson MS, Steinberger J, Roc- Predictivity of thyroid autoantibodies kinen AM, Vuori K, Salonen O, Sum- chini AP, Hayman LL, Daniels SR, Amer- for the development of thyroid disor- manen P, Yki-Jarvinen H, Kaste M, ¨ ican Heart Association Atherosclerosis, ders in children and adolescents with Heikkinen S, Lundbom N, Roine RO. Hypertension, and Obesity in Youth Type 1 diabetes. Diabet Med 2002;19: Brain metabolic alterations in patients Committee, American Heart Association 518 –521 with type 1 diabetes-hyperglycemia-in- Council of Cardiovascular Disease in the 330. Mohn A, Di Michele S, Di Luzio R, duced injury. J Cereb Blood Flow Metab Young, American Heart Association Tumini S, Chiarelli F. The effect of sub- 2004;24:1393–1399 Council on Cardiovascular Nursing. clinical hypothyroidism on metabolic315. 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- 331. Chase HP, Garg SK, Cockerham RS, 452– 457 pertension, and Obesity in Youth Wilcox WD, Walravens PA. Thyroid316. Jarvisalo MJ, Putto-Laurila A, Jartti L, ¨ Committee, 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– 498 321. Salo P, Viikari J, Hamalainen M, Lapin- ¨ ¨ ¨ 332. American Diabetes Association: Diabe-317. Haller MJ, Samyn M, Nichols WW, leimu H, Routi T, Ronnemaa T, Sep- ¨ tes care in the school and day care setting Brusko T, Wasserfall C, Schwartz RF, At- panen R, Jokinen E, Valimaki I, Simell ¨ ¨ ¨ (Position statement). Diabetes Care kinson M, Shuster JJ, Pierce GL, Silver- O. Serum cholesterol ester fatty acids in 2010;33(Suppl. 1):S70 –S74 stein JH. Radial artery tonometry 7- and 13-month-old children in a pro- 333. Bryden KS, Peveler RC, Stein A, Neil A, demonstrates arterial stiffness in chil- spective randomized trial of a low-satu- Mayou RA, Dunger DB. Clinical and dren with type 1 diabetes. Diabetes Care rated fat, low-cholesterol diet: the STRIP psychological course of diabetes from 2004;27:2911–2917 baby project. Special Turku coronary adolescence to young adulthood: a lon-318. Orchard TJ, Forrest KY, Kuller LH, Risk factor Intervention Project for chil- gitudinal cohort study. Diabetes Care Becker DJ, Pittsburgh Epidemiology of dren. Acta Paediatr 1999;88:505–512 2001;24:1536 –1540 Diabetes Complications Study. Lipid 322. Efficacy and safety of lowering dietary in- 334. Laing SP, Jones ME, Swerdlow AJ, Bur- and blood pressure treatment goals for take of fat and cholesterol in children with den AC, Gatling W. Psychosocial and so- type 1 diabetes: 10-year incidence data elevated low-density lipoprotein choles- cioeconomic risk factors for premature from the Pittsburgh Epidemiology of Di- terol. The Dietary Intervention Study in death in young people with type 1 dia- abetes Complications Study. Diabetes Children (DISC). The Writing Group for betes. Diabetes Care 2005;28:1618 – Care 2001;24:1053–1059 the DISC Collaborative Research Group. 1623319. Kavey RE, Allada V, Daniels SR, Hayman JAMA 1995;273:1429 –1435 335. Pacaud d, Yale Jf, Stephure D, Trussell R, LL, McCrindle BW, Newburger JW, 323. McCrindle BW, Ose L, Marais AD. Effi- Davies HD. Problems in transition from Parekh RS, Steinberger J, American cacy and safety of atorvastatin in chil- pediatric care to adult care for individu- Heart Association Expert Panel on Pop- dren and adolescents with familial als with diabetes. Can J Diabetes 2005; ulation and Prevention Science, Ameri- hypercholesterolemia or severe hyper- 29:13–18 can Heart Association Council on lipidemia: a multicenter, randomized, 336. American Academy of Pediatrics, Amer- Cardiovascular Disease in the Young, placebo-controlled trial. J Pediatr 2003; ican Academy of Family Physicians, American Heart Association Council on 143:74 – 80 American College of Physicians-Ameri- Epidemiology and Prevention, Ameri- 324. de Jongh S, Lilien MR, op’t Roodt J, can Society of Internal Medicine. A con- can Heart Association Council on Nutri- Stroes ES, Bakker HD, Kastelein JJ. Early sensus statement on health care tion, Physical Activity and Metabolism, statin therapy restores endothelial func- transitions fo ryoung adults with special American Heart Association Council on tion in children with familial hypercho- health care needs. Pediatrics 2002;110: High Blood Pressure Research, Ameri- lesterolemia. J Am Coll Cardiol 2002;40: 1304 –1306 can Heart Association Council on Car- 2117–2121 337. Wolpert HA, Anderson BJ, Weissberg- diovascular Nursing, American Heart 325. Wiegman A, Hutten BA, de Groot E, Ro- Benchell J: Transitions in care: Meeting the Association Council on the Kidney in denburg J, Bakker HD, Buller HR, Si- ¨ challenges of type 1 diabetes in young Heart Disease, Interdisciplinary Work- jbrands EJ, Kastelein JJ. Efficacy and adults. Alexandria VA, American Diabe- ing Group on Quality of Care and Out- safety of statin therapy in children with tes Association, 2009 comes Research. Cardiovascular risk familial hypercholesterolemia: a ran- 338. Eppens MC, Craig ME, Cusumano J, reduction in high-risk pediatric patients: domized controlled trial. JAMA 2004; Hing S, Chan AK, Howard NJ, Silink M, a scientific statement from the American 292:331–337 Donaghue KC. Prevalence of diabetes Heart Association Expert Panel on Pop- 326. Holmes GK. Screening for coeliac dis- complications in adolescents with type 2 ulation and Prevention Science; the ease in type 1 diabetes. Arch Dis Child compared with type 1 diabetes. Diabetes Councils on Cardiovascular Disease in 2002;87:495– 498 Care 2006;29:1300 –1306 the Young, Epidemiology and Preven- 327. Rewers M, Liu E, Simmons J, Redondo 339. Hattersley A, Bruining J, Shield J, Njols- tion, Nutrition, Physical Activity and MJ, Hoffenberg EJ: Celiac disease asso- tad P, Donaghue KC. The diagnosis andcare.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S59
    • Standards of Medical Care management of monogenic diabetes in Care 2009;32:1119 –1131 DR, Finfer S, Talmor D. Intensive insulin children and adolescents. Pediatr Diabe- 347. American Diabetes Association: Eco- therapy and mortality among critically tes 2009;12(Suppl.):33– 42 nomic costs of diabetes in the U.S. in ill patients: a meta-analysis including340. Cooper WO, Hernandez-Diaz S, Arbo- 2007. Diabetes Care 2008;31:596 – NICE-SUGAR study data. CMAJ 2009; gast PG, Dudley JA, Dyer S, Gideon PS, 615 180:821– 827 Hall K, Ray WA. Major congenital mal- 348. Levetan CS, Passaro M, Jablonski K, Kass 358. Saudek CD, Herman WH, Sacks DB, formations after first-trimester exposure M, Ratner RE. Unrecognized diabetes Bergenstal RM, Edelman D, Davidson to ACE inhibitors. N Engl J Med 2006; among hospitalized patients. Diabetes MB. A new look at screening and diag- 354:2443–2451 Care 1998;21:246 –249 nosing diabetes mellitus. J Clin Endocri-341. American Diabetes Association: Precon- 349. Umpierrez GE, Isaacs SD, Bazargan N, nol Metab 2008;93:2447–2453 ception care of women with diabetes You X, Thaler LM, Kitabchi AE. Hyper- 359. Cryer PE, Davis SN, Shamoon H. Hypo- (Position Statement). Diabetes Care glycemia: an independent marker of in- glycemia in diabetes. Diabetes Care 2004;27(Suppl. 1):S76 –S78 hospital mortality in patients with 2003;26:1902–1912342. Brown AF, Mangione CM, Saliba D, undiagnosed diabetes. J Clin Endocrinol 360. Czosnowski QA, Swanson JM, Lobo BL, Sarkisian CA, California Healthcare Metab 2002;87:978 –982 Broyles JE, Deaton PR, Finch CK. Eval- Foundation/American Geriatrics Society 350. van den Berghe G, Wouters P, Weekers uation of glycemic control following dis- Panel on Improving Care for Elders with F, Verwaest C, Bruyninckx F, Schetz M, continuation of an intensive insulin Diabetes. Guidelines for improving the Vlasselaers D, Ferdinande P, Lauwers P, protocol. J Hosp Med 2009;4:28 –34 care of the older person with diabetes Bouillon R. Intensive insulin therapy in 361. Shomali MI, Herr DL, Hill PC, Peh- mellitus. J Am Geriatr Soc 2003;51: the critically ill patients. N Engl J Med livanova M, Sharretts JM, and Magee MF S265–S280 2001;345:1359 –1367 Transition to Target: A prospective ran-343. Curb JD, Pressel SL, Cutler JA, Savage 351. Malmberg K, Norhammar A, Wedel H, domized trial comparing three formulae PJ, Applegate WB, Black H, Camel G, Ryden L. Glycometabolic state at admis- ´ for determination of subcutaneous basal Davis BR, Frost PH, Gonzalez N, Guthrie sion: important risk marker of mortality in insulin dosing at the time of transition G, Oberman A, Rutan GH, Stamler J. Ef- conventionally treated patients with dia- from intravenous insulin therapy follow- fect of diuretic-based antihypertensive betes mellitus and acute myocardial in- ing cardiac surgery. Diabetes Science treatment on cardiovascular disease risk farction: long-term results from the and Technology 2010. In press in older diabetic patients with isolated Diabetes and Insulin-Glucose Infusion in 362. Umpierrez GE, Smiley D, Jacobs S, Peng systolic hypertension. Systolic Hyper- Acute Myocardial Infarction (DIGAMI) L, Temponi A, Newton C, Umpierrez D, tension in the Elderly Program Cooper- study. Circulation 1999;99:2626 –2632 Mulligan P, Olson D, Mcleod J, Rizzo M. ative Research Group. JAMA 1996;276: 352. Wiener RS, Wiener DC, Larson RJ. Ben- Randomized study of basal bolus insulin 1886 –1892 efits and risks of tight glucose control in therapy in the inpatient management of344. Beckett NS, Peters R, Fletcher AE, Staes- critically ill adults: a meta-analysis. patients with type 2 diabetes undergoing sen JA, Liu L, Dumitrascu D, Stoy- JAMA 2008;300:933–944 general surgery (RABBIT 2 Surgery) (Ab- anovsky V, Antikainen RL, Nikitin Y, 353. Brunkhorst FM, Engel C, Bloos F, Meier- stract). Diabetes 2010;59(Suppl. 1):A9 Anderson C, Belhani A, Forette F, Raj- Hellmann A, Ragaller M, Weiler N, Mo- 363. Pasquel FJ, Spiegelman R, McCauley M, kumar C, Thijs L, Banya W, Bulpitt CJ, erer O, Gruendling M, Oppert M, Grond Smiley D, Umpierrez D, Johnson R, Rhee HYVET Study Group. Treatment of hy- S, Olthoff D, Jaschinski U, John S, Ros- M, Gatcliffe C, Lin E, Umpierrez E, Peng pertension in patients 80 years of age or saint R, Welte T, Schaefer M, Kern P, L, Umpierrez GE. Hyperglycemia during older. N Engl J Med 2008;358: Kuhnt E, Kiehntopf M, Hartog C, Natan- total parenteral nutrition: an important 1887–1898 son C, Loeffler M, Reinhart K, German marker of poor outcome and mortality344a.Moran A, Brunzell C, Cohen RC, Katz M, Competence Network Sepsis (SepNet). in hospitalized patients. Diabetes Care Marshall BC, Onady G, Robinson KA, Intensive insulin therapy and pen- 2010;33:739 –741 Sabadosa KA, Stecenko A, Slovis B; the tastarch resuscitation in severe sepsis. 364. Schnipper JL, Liang CL, Ndumele CD, CFRD Guidelines Committee. Clinical N Engl J Med 2008;358:125–139 Pendergrass ML. Effects of a computer- care guidelines for cystic fibrosis–related 354. NICE-SUGAR Study Investigators, Fin- ized order set on the inpatient manage- diabetes: a position statement of the fer S, Chittock DR, Su SY, Blair D, Foster ment of hyperglycemia: a cluster- American Diabetes Association and a D, Dhingra V, Bellomo R, Cook D, randomized controlled trial. Endocr clinical practice guideline of the Cystic Dodek P, Henderson WR, Hebert PC, ´ Pract 2010;16:209 –218 Fibrosis Foundation, endorsed by the Heritier S, Heyland DK, McArthur C, 365. Wexler DJ, Shrader P, Burns SM, Cagli- Pediatric Endocrine Society. Diabetes McDonald E, Mitchell I, Myburgh JA, ero E. Effectiveness of a computerized Care 2010;33:2697–2708 Norton R, Potter J, Robinson BG, Ronco insulin order template in general medi-345. Clement S, Braithwaite SS, Magee MF, JJ. Intensive versus conventional glucose cal inpatients with type 2 diabetes: a Ahmann A, Smith EP, Schafer RG, Hir- control in critically ill patients. N Engl cluster randomized trial. Diabetes Care sch IB, Hirsh IB, American Diabetes As- J Med 2009;360:1283–1297 2010;33:2181–2183 sociation Diabetes in Hospitals Writing 355. Krinsley JS, Grover A. Severe hypoglyce- 366. Furnary AP, Braithwaite SS. Effects of Committee. Management of diabetes mia in critically ill patients: risk factors outcome on in-hospital transition from and hyperglycemia in hospitals. Diabe- and outcomes. Crit Care Med 2007;35: intravenous insulin infusion to subcuta- tes Care 2004;27:553–591 2262–2267 neous therapy. Am J Cardiol 2006;98:346. Moghissi ES, Korytkowski MT, DiNardo 356. Van den Berghe G, Wilmer A, Hermans 557–564 M, Einhorn D, Hellman R, Hirsch IB, In- G, Meersseman W, Wouters PJ, Milants 367. Schafer RG, Bohannon B, Franz MJ, zucchi SE, Ismail-Beigi F, Kirkman MS, I, Van Wijngaerden E, Bobbaers H, Freeman J, Holmes A, McLaughlin S, Umpierrez GE, American Association of Bouillon R. Intensive insulin therapy in Haas LB, Kruger DF, Lorenz RA, McMa- Clinical Endocrinologists, American Dia- the medical ICU. N Engl J Med 2006; hon MM. Diabetes nutrition recommen- betes Association. American Association of 354:449 – 461 dations for health care institutions. Clinical Endocrinologists and American 357. Griesdale DE, de Souza RJ, van Dam RM, Diabetes Care 2004;27(Suppl. 1):S55– Diabetes Association consensus statement Heyland DK, Cook DJ, Malhotra A, S57 on inpatient glycemic control. Diabetes Dhaliwal R, Henderson WR, Chittock 368. Curll M, Dinardo M, Noschese M, Ko-S60 DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 care.diabetesjournals.org
    • Position Statement rytkowski MT. Menu selection, glycae- tions for glucose meters: assessment by by pharmacists-hypertension (SCRIP- mic control and satisfaction with simulation modeling of errors in insulin HTN). Arch Intern Med 2008;168: standard and patient-controlled consis- dose. Clin Chem 2001;47:209 –214 2355–2361 tent carbohydrate meal plans in hospi- 377. Shepperd S, McClaran J, Phillips CO, 387. Berikai P, Meyer PM, Kazlauskaite R, talised patients with diabetes. Qual Saf Lannin NA, Clemson LM, McCluskey A, Savoy B, Kozik K, Fogelfeld L. Gain in Health Care 2010;19:355–359 Cameron ID, Barras SL: Discharge plan- patients’ knowledge of diabetes man-369. American Diabetes Association: Diabe- ning from hospital to home. Cochrane agement targets is associated with bet- tes nutrition recommendations for Database Syst Rev CD000313, 2010 ter glycemic control. Diabetes Care health care institutions (Position State- 378. Agency for Healthcare Research and Qualtiy 2007;30:1587–1589 ment). Diabetes Care 2010;27(Suppl. [article online]. Available from http://psnet. 388. Sperl-Hillen JM, O’Connor PJ. Factors 1):S55–S57 ahrq.gov/primer.aspx?primerID 11. Ac- driving diabetes care improvement in a370. Boucher JL, Swift CS, Franz MJ, cessed 17 August 2010 large medical group: ten years of Kulkarni K, Schafer RG, Pritchett E, 379. Hoerger TJ, Segel JE, Gregg EW, Saad- progress. Am J Manag Care 2005;11: Clark NG. Inpatient management of di- dine JB. Is glycemic control improving in S177–S185 abetes and hyperglycemia: implications U.S. adults? Diabetes Care 2008;31: 389. Siminerio LM. Implementing diabetes for nutrition practice and the food and 81– 86 self-management training programs: nutrition professional. J Am Diet Assoc 380. Beaulieu N, Cutler DM, Ho K, Isham G, breaking through the barriers in primary 2007;107:105–111 Lindquist T, Nelson A, O’Connor P: the care. Endocr Pract 2006;12(Suppl. 1):371. Korytkowski MT, Salata RJ, Koerbel GL, business case for diabetes disease man- 124 –130 Selzer F, Karslioglu E, Idriss AM, Lee agement for managed care organiza- 390. Mahoney JJ. Reducing patient drug ac- KK, Moser AJ, Toledo FG. Insulin ther- tions. Forum for Health Economics and quisition costs can lower diabetes health apy and glycemic control in hospitalized Policy 2006;9:article 1 claims. Am J Manag Care 2005;11: patients with diabetes during enteral nu- 381. Cheung BM, Ong KL, Cherny SS, Sham S170 –S176 trition therapy: a randomized controlled PC, Tso AW, Lam KS. Diabetes preva- 391. Maney M, Tseng CL, Safford MM, Miller clinical trial. Diabetes Care 2009;32: lence and therapeutic target achieve- DR, Pogach LM. Impact of self-reported 594 –596 ment in the United States, 1999 to 2006. patient characteristics upon assessment372. Umpierrez GE. Basal versus sliding-scale Am J Med 2009;122:443– 453 of glycemic control in the Veterans regular insulin in hospitalized patients 382. Coleman K, Austin BT, Brach C, Wagner Health Administration. Diabetes Care with hyperglycemia during enteral nu- EH. Evidence on the Chronic Care trition therapy. Diabetes Care 2009;32: Model in the new millennium. Health 2007;30:245–251 751–753 Aff (Millwood) 2009;28:75– 85 392. Bergenstal RM. Treatment models from373. Klonoff DC, Perz JF. Assisted monitor- 383. O’Connor PJ. Electronic medical records the International Diabetes Center: ad- ing of blood glucose: special safety needs and diabetes care improvement: are we vancing from oral agents to insulin ther- for a new paradigm in testing glucose. J waiting for Godot? Diabetes Care 2003; apy in type 2 diabetes. Endocr Pract Diabetes Sci Technol 2010;4:1027– 26:942–943 2006;12(Suppl. 1):98 –104 1031 384. Shojania KG, Ranji SR, McDonald KM, 393. Feifer C, Nemeth L, Nietert PJ, Wessell374. D’Orazio P, Burnett RW, Fogh- Grimshaw JM, Sundaram V, Rushakoff AM, Jenkins RG, Roylance L, Ornstein Andersen N, Jacobs E, Kuwa K, Kulp- ¨ RJ, Owens DK. Effects of quality im- SM. Different paths to high-quality care: mann WR, Larsson L, Lewenstam A, provement strategies for type 2 diabetes three archetypes of top-performing Maas AH, Mager G, Naskalski JW, on glycemic control: a meta-regression practice sites. Ann Fam Med 2007; Okorodudu AO, International Federa- analysis. JAMA 2006;296:427– 440 5:233–241 tion of Clinical Chemistry Scientific Di- 385. Davidson MB. How our current medical 394. Ornstein S, Nietert PJ, Jenkins RG, Wes- vision Working Group on Selective care system fails people with diabetes: sell AM, Nemeth LS, Feifer C, Corley ST. Electrodes and Point of Care Testing. lack of timely, appropriate clinical deci- Improving diabetes care through a Approved IFCC recommendation on re- sions. Diabetes Care 2009;32:370 –372 multicomponent quality improvement porting results for blood glucose (abbre- 386. McLean DL, McAlister FA, Johnson JA, model in a practice-based research net- viated). Clin Chem 2005;51:1573–1576 King KM, Makowsky MJ, Jones CA, work. Am J Med Qual 2007;22:34 – 41375. Dungan K, Chapman J, Braithwaite SS, Tsuyuki RT, SCRIP-HTN Investigators. 395. Parchman ML, Zeber JE, Romero RR, Buse J. Glucose measurement: con- A randomized trial of the effect of com- Pugh JA. Risk of coronary artery disease in founding issues in setting targets for in- munity pharmacist and nurse care on type 2 diabetes and the delivery of care patient management. Diabetes Care improving blood pressure management consistent with the chronic care model in 2007;30:403– 409 in patients with diabetes mellitus: study primary care settings: a STARNet study.376. Boyd JC, Bruns DE. Quality specifica- of cardiovascular risk intervention Med Care 2007;45:1129 –1134care.diabetesjournals.org DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011 S61