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  • 1. P O S I T I O N S T A T E M E N TStandards of Medical Care inDiabetesd2012D iabetes mellitus is a chronic illness new evidence. For the current revision, c Type 1 diabetes (results from b-cell that requires continuing medical care committee members systematically searched destruction, usually leading to absolute and ongoing patient self-management Medline for human studies related to each insulin deficiency)education and support to prevent acute subsection and published since 1 January c Type 2 diabetes (results from a pro-complications and to reduce the risk of 2010. Recommendations (bulleted at the gressive insulin secretory defect on thelong-term complications. Diabetes care is beginning of each subsection and also listed background of insulin resistance)complex and requires that many issues, in the “Executive Summary: Standards of c Other specific types of diabetes due tobeyond glycemic control, be addressed. Medical Care in Diabetesd2012”) were re- other causes, e.g., genetic defects in b-cellA large body of evidence exists that sup- vised based on new evidence or, in some function, genetic defects in insulin action,ports a range of interventions to improve cases, to clarify the prior recommendation diseases of the exocrine pancreas (such asdiabetes outcomes. or match the strength of the wording to cystic fibrosis), and drug- or chemical- These standards of care are intended the strength of the evidence. A table link- induced (such as in the treatment of HIV/to provide clinicians, patients, researchers, ing the changes in recommendations to AIDS or after organ transplantation)payers, and other interested individuals new evidence can be reviewed at http:// c Gestational diabetes mellitus (GDM)with the components of diabetes care, professional.diabetes.org/CPR_Search. (diabetes diagnosed during pregnancygeneral treatment goals, and tools to eval- aspx. Subsequently, as is the case for all that is not clearly overt diabetes)uate the quality of care. While individual Position Statements, the standards of carepreferences, comorbidities, and other pa- were reviewed and approved by the Execu- Some patients cannot be clearly clas-tient factors may require modification of tive Committee of ADA’s Board of Directors, sified as having type 1 or type 2 diabetes.goals, targets that are desirable for most which includes health care professionals, Clinical presentation and disease progres-patients with diabetes are provided. Spe- scientists, and lay people. sion vary considerably in both types ofcifically titled sections of the standards Feedback from the larger clinical com- diabetes. Occasionally, patients who oth-address children with diabetes, pregnant munity was valuable for the 2012 revision erwise have type 2 diabetes may presentwomen, and people with prediabetes. These of the standards. Readers who wish to with ketoacidosis. Similarly, patients withstandards are not intended to preclude comment on the “Standards of Medical type 1 may have a late onset and slow (butclinical judgment or more extensive eval- Care in Diabetesd2012” are invited to do relentless) progression of disease despiteuation and management of the patient by so at http://professional.diabetes.org/ having features of autoimmune disease.other specialists as needed. For more de- CPR_Search.aspx. Such difficulties in diagnosis may occurtailed information about management of Members of the Professional Practice in children, adolescents, and adults. Thediabetes, refer to references 1–3. Committee disclose all potential financial true diagnosis may become more obvious The recommendations included are conflicts of interest with industry. These over time.screening, diagnostic, and therapeutic ac- disclosures were discussed at the onset oftions that are known or believed to favor- the standards revision meeting. Members of B. Diagnosis of diabetesably affect health outcomes of patients with the committee, their employer, and their Recommendationsdiabetes. A large number of these interven- disclosed conflicts of interest are listed in the For decades, the diagnosis of diabetes wastions have been shown to be cost-effective “Professional Practice Committee Members” based on plasma glucose criteria, either(4). A grading system (Table 1), developed table (see pg. S109). The American Diabetes the fasting plasma glucose (FPG) or theby the American Diabetes Association Association funds development of the 2-h value in the 75-g oral glucose toler-(ADA) and modeled after existing methods, standards and all its position statements ance test (OGTT) (5).was utilized to clarify and codify the evi- out of its general revenues and does not uti- In 2009, an International Expert Com-dence that forms the basis for the recom- lize industry support for these purposes. mittee that included representatives of themendations. The level of evidence that American Diabetes Association (ADA), thesupports each recommendation is listed af- I. CLASSIFICATION AND International Diabetes Federation (IDF),ter each recommendation using the letters DIAGNOSIS and the European Association for the StudyA, B, C, or E. of Diabetes (EASD) recommended the use These standards of care are revised an- A. Classification of the A1C test to diagnose diabetes,nually by the ADA’s multidisciplinary Pro- The classification of diabetes includes four with a threshold of $6.5% (6), and ADAfessional Practice Committee, incorporating clinical classes: adopted this criterion in 2010 (5). The di- agnostic test should be performed using ac c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c method that is certified by the NationalOriginally approved 1988. Most recent review/revision October 2011. Glycohemoglobin Standardization Pro-DOI: 10.2337/dc12-s011© 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly gram (NGSP) and standardized or traceable cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/ to the Diabetes Control and Complications licenses/by-nc-nd/3.0/ for details. Trial (DCCT) reference assay. Point-of-carecare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S11
  • 2. Position StatementTable 1dADA evidence grading system for clinical practice recommendations Table 2dCriteria for the diagnosis of diabetesLevel of A1C $6.5%. The test should be performedevidence Description in a laboratory using a method that is NGSP certified and standardized to the DCCTA Clear evidence from well-conducted, generalizable, RCTs that are adequately assay.* powered, including: OR c Evidence from a well-conducted multicenter trial FPG $126 mg/dL (7.0 mmol/L). Fasting is c Evidence from a meta-analysis that incorporated quality ratings in the analysis defined as no caloric intake for at least 8 h.* Compelling nonexperimental evidence, i.e., “all or none” rule developed OR by Center for Evidence Based Medicine at Oxford 2-h plasma glucose $200 mg/dL (11.1 mmol/L) Supportive evidence from well-conducted randomized controlled trials that during an OGTT. The test should be are adequately powered, including: performed as described by the WHO, using c Evidence from a well-conducted trial at one or more institutions a glucose load containing the equivalent of c Evidence from a meta-analysis that incorporated quality ratings in 75 g anhydrous glucose dissolved in water.* the analysis ORB Supportive evidence from well-conducted cohort studies In a patient with classic symptoms of c Evidence from a well-conducted prospective cohort study or registry hyperglycemia or hyperglycemic crisis, a random plasma glucose $200 mg/dL c Evidence from a well-conducted meta-analysis of cohort studies (11.1 mmol/L) Supportive evidence from a well-conducted case-control studyC *In the absence of unequivocal hyperglycemia, re- Supportive evidence from poorly controlled or uncontrolled studies sult should be confirmed by repeat testing. c Evidence from RCTs with one or more major or three or more minor methodological flaws that could invalidate the results c Evidence from observational studies with high potential for bias of undiagnosed diabetes than a fasting (such as case series with comparison with historical controls) glucose cut point of $126 mg/dL (7.0 c Evidence from case series or case reports mmol/L) (11). However, in practice, a Conflicting evidence with the weight of evidence supporting the recommendation large portion of the diabetic populationE Expert consensus or clinical experience remains unaware of their condition. Thus, the lower sensitivity of A1C at the designated cut point may well be offset byA1C assays, for which proficiency testing is postprandially) may be higher (9). Epide- the test’s greater practicality, and widernot mandated, are not sufficiently accurate miologic studies forming the framework application of a more convenient testat this time to use for diagnostic purposes. for recommending use of the A1C to diag- (A1C) may actually increase the number Epidemiologic datasets show a similar nose diabetes have all been in adult popu- of diagnoses made.relationship between A1C and risk of lations. Whether the cut point would be As with most diagnostic tests, a testretinopathy as has been shown for the the same to diagnose children with type 2 result diagnostic of diabetes should becorresponding FPG and 2-h PG thresholds. diabetes is an area of uncertainty (10). A1C repeated to rule out laboratory error, unlessThe A1C has several advantages to the FPG inaccurately reflects glycemia with certain the diagnosis is clear on clinical grounds,and OGTT, including greater convenience anemias and hemoglobinopathies. For pa- such as a patient with a hyperglycemic(since fasting is not required), evidence to tients with an abnormal hemoglobin but crisis or classic symptoms of hyperglycemiasuggest greater preanalytical stability, and normal red cell turnover, such as sickle cell and a random plasma glucose $200 mg/dL.less day-to-day perturbations during pe- trait, an A1C assay without interference from It is preferable that the same test be repeatedriods of stress and illness. These advan- abnormal hemoglobins should be used (an for confirmation, since there will be a greatertages must be balanced by greater cost, updated list is available at www.ngsp.org/ likelihood of concurrence in this case. Forthe limited availability of A1C testing in npsp.org/interf.asp). For conditions with ab- example, if the A1C is 7.0% and a repeatcertain regions of the developing world, normal red cell turnover, such as pregnancy, result is 6.8%, the diagnosis of diabetes isand the incomplete correlation between recent blood loss or transfusion, or some confirmed. However, if two different testsA1C and average glucose in certain indi- anemias, the diagnosis of diabetes must em- (such as A1C and FPG) are both above theviduals. In addition, HbA1c levels may vary ploy glucose criteria exclusively. diagnostic thresholds, the diagnosis of dia-with patients’ race/ethnicity (7,8). Some The established glucose criteria for betes is also confirmed.have posited that glycation rates differ by the diagnosis of diabetes (FPG and 2-h On the other hand, if two differentrace (with, for example, African Americans PG) remain valid as well (Table 2). Just as tests are available in an individual andhaving higher rates of glycation), but this there is less than 100% concordance be- the results are discordant, the test whoseis controversial. A recent epidemiologic tween the FPG and 2-h PG tests, there is result is above the diagnostic cut pointstudy found that, when matched for FPG, not perfect concordance between A1C should be repeated, and the diagnosis isAfrican Americans (with and without di- and either glucose-based test. Analyses made on the basis of the confirmed test.abetes) indeed had higher A1C than of National Health and Nutrition Exami- That is, if a patient meets the diabeteswhites, but also had higher levels of fruc- nation Survey (NHANES) data indicate criterion of the A1C (two results $6.5%)tosamine and glycated albumin and lower that, assuming universal screening of but not the FPG (,126 mg/dL or 7.0levels of 1,5-anhydroglucitol, suggesting the undiagnosed, the A1C cut point of mmol/L), or vice versa, that person shouldthat their glycemic burden (particularly $6.5% identifies one-third fewer cases be considered to have diabetes.S12 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 3. Position Statement Since there is preanalytic and analytic with an A1C of 5.0% (14). In a community- Table 3dCategories of increased risk forvariability of all the tests, it is also possible based study of black and white adults with- diabetes (prediabetes)*that when a test whose result was above out diabetes, baseline A1C was a stronger FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dLthe diagnostic threshold is repeated, the predictor of subsequent diabetes and car- (6.9 mmol/L) (IFG)second value will be below the diagnostic diovascular events than fasting glucose ORcut point. This is least likely for A1C, (15). Other analyses suggest that an A1C 2-h plasma glucose in the 75-g OGTTsomewhat more likely for FPG, and most of 5.7% is associated with diabetes risk sim- 140 mg/dL (7.8 mmol/L) to 199 mg/dLlikely for the 2-h PG. Barring a laboratory ilar to that of the high-risk participants in (11.0 mmol/L) (IGT)error, such patients are likely to have test the Diabetes Prevention Program (DPP). ORresults near the margins of the threshold Hence, it is reasonable to consider an A1C 5.7–6.4%for a diagnosis. The health care professional A1C range of 5.7 to 6.4% as identifying *For all three tests, risk is continuous, extendingmight opt to follow the patient closely and individuals with high risk for future below the lower limit of the range and becomingrepeat the testing in 3–6 months. The cur- diabetes, a state that may be referred to disproportionately greater at higher ends of the range.rent diagnostic criteria for diabetes are as prediabetes (5). As is the case for indi-summarized in Table 2. viduals found to have IFG and IGT, indi- viduals with an A1C of 5.7–6.4% should the provider tests because of high suspicionC. Categories of increased risk for be informed of their increased risk for di- of diabetes, to the symptomatic patient.diabetes (prediabetes) abetes as well as CVD and counseled The discussion herein is primarily framedIn 1997 and 2003, The Expert Committee about effective strategies to lower their as testing for diabetes in those withouton Diagnosis and Classification of Diabetes risks (see section IV. PREVENTION/ symptoms. The same assays used for test-Mellitus (12,13) recognized an interme- DELAY OF TYPE 2 DIABETES). As with ing for diabetes will also detect individualsdiate group of individuals whose glucose glucose measurements, the continuum of with prediabetes.levels, although not meeting criteria for risk is curvilinear, so that as A1C rises thediabetes, are nevertheless too high to be risk of diabetes rises disproportionately A. Testing for type 2 diabetes andconsidered normal. These persons were (14). Accordingly, interventions should risk of future diabetes in adultsdefined as having impaired fasting glu- be most intensive and follow-up should Prediabetes and diabetes meet establishedcose (IFG) (FPG levels 100 mg/dL [5.6 be particularly vigilant for those with criteria for conditions in which early de-mmol/L] to 125 mg/dL [6.9 mmol/L]), A1Cs .6.0%, who should be considered tection is appropriate. Both conditions areor impaired glucose tolerance (IGT) (2-h to be at very high risk. Table 3 summarizes common, increasing in prevalence, andvalues in the OGTT of 140 mg/dL [7.8 the categories of increased risk for diabetes. impose significant public health burdens.mmol/L] to 199 mg/dL [11.0 mmol/L]). It There is a long presymptomatic phaseshould be noted that the World Health II. TESTING FOR DIABETES IN before the diagnosis of type 2 diabetes isOrganization (WHO) and a number of ASYMPTOMATIC PATIENTS usually made. Relatively simple tests areother diabetes organizations define the cut- available to detect preclinical disease. Ad-off for IFG at 110 mg/dL (6.1 mmol/L). Recommendations ditionally, the duration of glycemic burden Individuals with IFG and/or IGT have c Testing to detect type 2 diabetes and is a strong predictor of adverse outcomes,been referred to as having prediabetes, assess risk for future diabetes in asymp- and effective interventions exist to preventindicating the relatively high risk for the tomatic people should be considered in progression of prediabetes to diabetes (seefuture development of diabetes. IFG and adults of any age who are overweight or section IV. PREVENTION/DELAY OFIGT should not be viewed as clinical obese (BMI $25 kg/m2) and who have TYPE 2 DIABETES) and to reduce risk ofentities in their own right but rather risk one or more additional risk factors for complications of diabetes (see section V.I.factors for diabetes as well as cardiovascular diabetes (Table 4). In those without PREVENTION AND MANAGEMENT OFdisease (CVD). IFG and IGT are associated these risk factors, testing should begin at DIABETES COMPLICATIONS).with obesity (especially abdominal or vis- age 45 years. (B) Type 2 diabetes is frequently notceral obesity), dyslipidemia with high tri- c If tests are normal, repeat testing at least diagnosed until complications appear,glycerides and/or low HDL cholesterol, and at 3-year intervals is reasonable. (E) and approximately one-fourth of all peoplehypertension. c To test for diabetes or to assess risk with diabetes in the U.S. may be undiag- As is the case with the glucose meas- of future diabetes, the A1C, FPG, or 2-h nosed. The effectiveness of early identifica-ures, several prospective studies that used 75-g OGTT are appropriate. (B) tion of prediabetes and diabetes throughA1C to predict the progression to diabetes c In those identified with increased risk mass testing of asymptomatic individualsdemonstrated a strong, continuous asso- for future diabetes, identify and, if appro- has not been proven definitively, andciation between A1C and subsequent di- priate, treat other CVD risk factors. (B) rigorous trials to provide such proof areabetes. In a systematic review of 44,203 unlikely to occur. In a large randomizedindividuals from 16 cohort studies with a For many illnesses, there is a major controlled trial (RCT) in Europe, generalfollow-up interval averaging 5.6 years distinction between screening and diag- practice patients between the ages of 40(range 2.8-12 years), those with an A1C nostic testing. However, for diabetes, the and 69 years were screened for diabetesbetween 5.5 and 6.0% had a substantially same tests would be used for “screening” and then randomized by practice to routineincreased risk of diabetes with 5-year in- as for diagnosis. Diabetes may be identified care of diabetes or intensive treatment ofcidences ranging from 9–25%. An A1C anywhere along a spectrum of clinical sce- multiple risk factors. After 5.3 years ofrange of 6.0 to 6.5% had a 5-year risk of narios ranging from a seemingly low-risk follow-up, CVD risk factors were modestlydeveloping diabetes between 25 to 50% individual who happens to have glucose but significantly more improved with in-and relative risk 20 times higher compared testing, to a higher-risk individual whom tensive treatment. Incidence of first CVDcare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S13
  • 4. Position StatementTable 4dCriteria for testing for diabetes in asymptomatic adult individuals Because of the need for follow-up and discussion of abnormal results, testing1. Testing should be considered in all adults who are overweight (BMI $25 kg/m2*) and who should be carried out within the health have one or more additional risk factors: care setting. Community screening outside c physical inactivity a health care setting is not recommended c first-degree relative with diabetes because people with positive tests may not c high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, seek, or have access to, appropriate follow- Pacific Islander) up testing and care. Conversely, there may c women who delivered a baby weighing .9 lb or who were diagnosed with GDM be failure to ensure appropriate repeat c hypertension (blood pressure $140/90 mmHg or on therapy for hypertension) testing for individuals who test negative. c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level .250 mg/dL Community screening may also be poorly (2.82 mmol/L) targeted, i.e., it may fail to reach the groups c women with PCOS most at risk and inappropriately test those at low risk (the worried well) or even those c A1C $5.7%, IGT, or IFG on previous testing already diagnosed. c other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) B. Testing for type 2 diabetes c history of CVD in children2. In the absence of the above criteria, testing for diabetes should begin at age 45 years The incidence of type 2 diabetes in ado-3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration lescents has increased dramatically in the of more-frequent testing depending on initial results (e.g., those with prediabetes should be last decade, especially in minority popu- tested yearly) and risk status. lations (28), although the disease remains*At-risk BMI may be lower in some ethnic groups. PCOS, polycystic ovary syndrome. rare in the general pediatric population (29). Consistent with recommendationsevent and mortality rates were not signifi- Either A1C, FPG, or the 2-h OGTT is for adults, children and youth at in-cantly different between groups (16). This appropriate for testing. It should be noted creased risk for the presence or the devel-study would seem to add support for early that the tests do not necessarily detect opment of type 2 diabetes should betreatment of screen-detected diabetes, as diabetes in the same individuals. The ef- tested within the healthcare setting (30).risk factor control was excellent even in ficacy of interventions for primary pre- The recommendations of the ADA con-the routine treatment arm and both groups vention of type 2 diabetes (20–26) has sensus statement on Type 2 Diabetes inhad lower event rates than predicted. The primarily been demonstrated among in- Children and Youth, with some modifica-absence of a control unscreened arm limits dividuals with IGT, not for individuals tions, are summarized in Table 5 (30).the ability to definitely prove that screening with isolated IFG or for individuals withimpacts outcomes. Mathematical modeling specific A1C levels. C. Screening for type 1 diabetesstudies suggest that screening independent The appropriate interval between Generally, people with type 1 diabetesof risk factors beginning at age 30 or age 45 tests is not known (27). The rationale present with acute symptoms of diabetesyears is highly cost-effective (,$11,000 for the 3-year interval is that false nega- and markedly elevated blood glucoseper quality-adjusted life-year gained) (17). tives will be repeated before substantial levels, and most cases are diagnosed soon Recommendations for testing for di- time elapses, and there is little likelihood after the onset of hyperglycemia. However,abetes in asymptomatic, undiagnosed that an individual will develop significant evidence from type 1 prevention studiesadults are listed in Table 4. Testing should complications of diabetes within 3 years suggests that measurement of islet auto-be considered in adults of any age with of a negative test result. In the modeling antibodies identifies individuals who are atBMI $25 kg/m2 and one or more of the study, repeat screening every 3 or 5 years risk for developing type 1 diabetes. Suchknown risk factors for diabetes. There is was cost-effective (17). testing may be appropriate in high-riskcompelling evidence that lower BMI cutpoints suggest diabetes risk in some racialand ethnic groups. In a large multiethnic Table 5dTesting for type 2 diabetes in asymptomatic childrencohort study, for an equivalent incidence Criteriarate of diabetes conferred by a BMI of 30 c Overweight (BMI .85th percentile for age and sex, weight for height .85thkg/m2 in whites, the BMI cutoff value was percentile, or weight .120% of ideal for height24 kg/m2 in South Asians, 25 kg/m2 in Plus any two of the following risk factors:Chinese, and 26 kg/m2 African Americans c Family history of type 2 diabetes in first- or second-degree relative(18).Disparities in screening rates, not ex- c Race/ethnicity (Native American, African American, Latino, Asian American,plainable by insurance status, are high-lighted by evidence that despite much Pacific Islander)higher prevalence of type 2 diabetes, c Signs of insulin resistance or conditions associated with insulin resistancenon-Caucasians in an insured population (acanthosis nigricans, hypertension, dyslipidemia, PCOS, or birth weight small forare no more likely than Caucasians to be gestational age birthweight)screened for diabetes (19). Because age c Maternal history of diabetes or GDM during the child’s gestationis a major risk factor for diabetes, testing Age of initiation: 10 years or at onset of puberty, if puberty occurs at a younger ageof those without other risk factors should Frequency: every 3 yearsbegin no later than age 45 years. PCOS, polycystic ovary syndromeS14 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 5. Position Statementindividuals, such as those with prior tran- onset or first recognition during preg- pregnancies previously categorized assient hyperglycemia or those who have nancy (12), whether or not the condition normal. These diagnostic criteria changesrelatives with type 1 diabetes, in the context persisted after pregnancy, and not exclud- are being made in the context of worri-of clinical research studies (see, e.g., http:// ing the possibility that unrecognized glu- some worldwide increases in obesity andwww2.diabetestrialnet.org). Widespread cose intolerance may have antedated or diabetes rates, with the intent of optimiz-clinical testing of asymptomatic low-risk in- begun concomitantly with the pregnancy. ing gestational outcomes for women anddividuals cannot currently be recommended, This definition facilitated a uniform strat- their babies.as it would identify very few individuals in egy for detection and classification of GDM, Admittedly, there are few data fromthe general population who are at risk. In- but its limitations were recognized for randomized clinical trials regarding ther-dividuals who screen positive should be many years. As the ongoing epidemic of apeutic interventions in women who willcounseled about their risk of developing di- obesity and diabetes has led to more type now be diagnosed with GDM based onabetes. Clinical studies are being conducted 2 diabetes in women of childbearing age, only one blood glucose value above theto test various methods of preventing type 1 the number of pregnant women with un- specified cut points (in contrast to thediabetes, or reversing early type 1 diabetes, diagnosed type 2 diabetes has increased older criteria that stipulated at least twoin those with evidence of autoimmunity. (31). Because of this, it is reasonable to abnormal values). However, there is emerg- screen women with risk factors for type 2 ing observational and retrospective evi-III. DETECTION AND diabetes (Table 4) for diabetes at their initial dence that women diagnosed with theDIAGNOSIS OF GESTATIONAL prenatal visit, using standard diagnostic new criteria (even if they would not haveDIABETES MELLITUS (GDM) criteria (Table 2). Women found to have been diagnosed with older criteria) have diabetes at this visit should receive a di- increased rates of poor pregnancy outcomesRecommendations agnosis of overt, not gestational, diabetes. similar to those of women with GDM byc Screen for undiagnosed type 2 diabetes GDM carries risks for the mother and prior criteria (34,35). Expected benefits at the first prenatal visit in those with risk neonate. The Hyperglycemia and Adverse to these pregnancies and offspring is infer- factors, using standard diagnostic crite- Pregnancy Outcomes (HAPO) study (32), a red from intervention trials that focused on ria. (B) large-scale (;25,000 pregnant women) women with more mild hyperglycemiac In pregnant women not previously multinational epidemiologic study, dem- than identified using older GDM diagnostic known to have diabetes, screen for GDM onstrated that risk of adverse maternal, fe- criteria and that found modest benefits at 24–28 weeks’ gestation, using a 75-g tal, and neonatal outcomes continuously (36,37). The frequency of follow-up and 2-h OGTT and the diagnostic cut points increased as a function of maternal glyce- blood glucose monitoring for these women in Table 6. (B) mia at 24–28 weeks, even within ranges is not yet clear but likely to be less intensivec Screen women with GDM for persistent previously considered normal for preg- than for women diagnosed by the older cri- diabetes at 6–12 weeks’ postpartum, nancy. For most complications, there was teria. It is important to note that 80–90% of using a test other than A1C. (E) no threshold for risk. These results have led women in both of the mild GDM studiesc Women with a history of GDM should to careful reconsideration of the diagnostic (whose glucose values overlapped with the have lifelong screening for the devel- criteria for GDM. After deliberations in thresholds recommended herein) could be opment of diabetes or prediabetes at 2008–2009, the International Association managed with lifestyle therapy alone. least every 3 years. (B) of Diabetes and Pregnancy Study Groups The American College of Obstetricsc Women with a history of GDM found (IADPSG), an international consensus and Gynecology announced in 2011 that to have prediabetes should receive life- group with representatives from multiple they continue to recommend use of prior style interventions or metformin to pre- obstetrical and diabetes organizations, in- diagnostic criteria for GDM (38). Several vent diabetes. (A) cluding ADA, developed revised recom- other countries have adopted the new cri- mendations for diagnosing GDM. The teria, and a report from the WHO on this For many years, GDM was defined as group recommended that all women not topic is pending at the time of the publi-any degree of glucose intolerance with known to have prior diabetes undergo a cation of these standards. 75-g OGTT at 24–28 weeks of gestation. Because some cases of GDM may rep- Additionally, the group developed diag- resent preexisting undiagnosed type 2Table 6dScreening for and diagnosis of nostic cut points for the fasting, 1-h, and diabetes, women with a history of GDMGDM 2-h plasma glucose measurements that should be screened for diabetes 6–12Perform a 75-g OGTT, with plasma glucose conveyed an odds ratio for adverse out- weeks’ postpartum, using nonpregnant measurement fasting and at 1 and 2 h, at comes of at least 1.75 compared with OGTT criteria. Because of their prepartum 24–28 weeks’ gestation in women not women with the mean glucose levels in treatment for hyperglycemia, use of the previously diagnosed with overt diabetes. the HAPO study. Current screening and A1C for diagnosis of persistent diabetes at diagnostic strategies, based on the IADPSG the postpartum visit is not recommendedThe OGTT should be performed in the statement (33), are outlined in Table 6. (39). Women with a history of GDM have a morning after an overnight fast of at least These new criteria will significantly greatly increased subsequent risk for diabe- 8 h. increase the prevalence of GDM, primar- tes (40) and should be followed up withThe diagnosis of GDM is made when any of ily because only one abnormal value, not subsequent screening for the development the following plasma glucose values are two, is sufficient to make the diagnosis. of diabetes or prediabetes, as outlined in exceeded: ADA recognizes the anticipated signifi- section II. TESTING FOR DIABETES IN c Fasting $92 mg/dL (5.1 mmol/L) cant increase in the incidence of GDM ASYMPTOMATIC PATIENTS. c 1 h $180 mg/dL (10.0 mmol/L) diagnosed by these criteria and is sensitive Lifestyle interventions or metformin c 2 h $153 mg/dL (8.5 mmol/L) to concerns about the “medicalization” of should be offered to women with a historycare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S15
  • 6. Position Statementof GDM who develop prediabetes, as Based on the results of clinical trials The management plan should bediscussed in section IV. PREVENTION/ and the known risks of progression of formulated as a collaborative therapeuticDELAY OF TYPE 2 DIABETES. prediabetes to diabetes, persons with an alliance among the patient and family, A1C of 5.7–6.4%, IGT, or IFG should be the physician, and other members of theIV. PREVENTION/DELAY counseled on lifestyle changes with goals health care team. A variety of strategiesOF TYPE 2 DIABETES similar to those of the DPP (7% weight and techniques should be used to provide loss and moderate physical activity of at adequate education and developmentRecommendations least 150 min per week). Regarding drug of problem-solving skills in the variousc Patients with IGT (A), IFG (E), or an A1C therapy for diabetes prevention, a consen- aspects of diabetes management. Imple- of 5.7–6.4% (E) should be referred to an sus panel felt that metformin should be mentation of the management plan re- effective ongoing support program tar- the only drug considered (47). For other quires that each aspect is understood and geting weight loss of 7% of body weight drugs, issues of cost, side effects, and lack agreed to by the patient and the care and increasing physical activity to at least of persistence of effect in some studies providers and that the goals and treatment 150 min per week of moderate activity (48) require consideration. Metformin plan are reasonable. Any plan should rec- such as walking. was less effective than lifestyle interven- ognize diabetes self-management educationc Follow-up counseling appears to be im- tion in the DPP and DPPOS but may be (DSME) and on-going diabetes support as portant for success. (B) cost-saving over a 10-year period (45). It an integral component of care. In develop-c Based on the cost-effectiveness of dia- was as effective as lifestyle in participants ing the plan, consideration should be given betes prevention, such programs should with a BMI of at least 35 kg/m2 (20), and to the patient’s age, school or work schedule be covered by third-party payers. (B) in women with a history of GDM, metfor- and conditions, physical activity, eatingc Metformin therapy for prevention of min and intensive lifestyle led to an equiv- patterns, social situation and cultural fac- type 2 diabetes may be considered in alent 50% reduction in the risk of diabetes tors, and presence of complications of those with IGT (A), IFG (E), or an A1C (49). Metformin therefore might reason- diabetes or other medical conditions. of 5.7–6.4% (E), especially for those with ably be recommended for very-high-risk BMI .35 kg/m2, age ,60 years, and individuals (those with a history of GDM, C. Glycemic control women with prior GDM. (A) the very obese, and/or those with more 1. Assessment of glycemic control. Twoc At least annual monitoring for the de- severe or progressive hyperglycemia). Of primary techniques are available for health velopment of diabetes in those with note in the DPP, metformin was not sig- providers and patients to assess the ef- prediabetes is suggested. (E) nificantly better than placebo in those fectiveness of the management plan on over age 60 years. glycemic control: patient self-monitoring of RCTs have shown that individuals at blood glucose (SMBG) or interstitial glu-high risk for developing type 2 diabetes V. DIABETES CARE cose, and A1C.(those with IFG, IGT, or both) can signif-icantly decrease the rate of onset of diabetes a. Glucose monitoring A. Initial evaluationwith particular interventions (20–26). A complete medical evaluation should be RecommendationsThese include intensive lifestyle modifica- c SMBG should be carried out three or performed to classify the diabetes, detecttion programs that have been shown to more times daily for patients using mul- the presence of diabetes complications,be very effective (;58% reduction after tiple insulin injections or insulin pump review previous treatment and glycemic3 years) and use of the pharmacologic therapy. (B) control in patients with established diabetes,agents metformin, a glucosidase inhibi- c For patients using less-frequent in- assist in formulating a management plan,tors, orlistat, and thiazolidinediones, sulin injections, noninsulin therapies, and provide a basis for continuing care.each of which has been shown to decrease or medical nutrition therapy (MNT) Laboratory tests appropriate to the evalua-incident diabetes to various degrees. Follow- alone, SMBG may be useful as a guide tion of each patient’s medical conditionup of three large studies of lifestyle inter- to management. (E) should be performed. A focus on the com-vention has shown sustained reduction in ponents of comprehensive care (Table 7) c To achieve postprandial glucose targets,the rate of conversion to type 2 diabetes, postprandial SMBG may be appropriate. will assist the health care team to ensurewith 43% reduction at 20 years in the Da (E) optimal management of the patient withQing study (41), 43% reduction at 7 years c When prescribing SMBG, ensure that diabetes.in the Finnish Diabetes Prevention Study patients receive initial instruction in,(DPS) (42), and 34% reduction at 10 and routine follow-up evaluation of,years in the U.S. Diabetes Prevention Pro- B. Management SMBG technique and their ability to usegram Outcome Study (DPPOS) (43). A People with diabetes should receive med- data to adjust therapy. (E)cost-effectiveness model suggested that ical care from a physician-coordinated c Continuous glucose monitoring (CGM)lifestyle interventions as delivered in the team. Such teams may include, but are in conjunction with intensive insulinDPP are cost-effective (44), and actual not limited to, physicians, nurse practition- regimens can be a useful tool to lowercost data from the DPP and DPPOS con- ers, physician’s assistants, nurses, dietitians, A1C in selected adults (age $25 years)firm that lifestyle interventions are highly pharmacists, and mental health professio- with type 1 diabetes. (A)cost-effective (45). Group delivery of the nals with expertise and a special interest in c Although the evidence for A1C-loweringDPP intervention in community settings diabetes. It is essential in this collaborative is less strong in children, teens, andhas the potential to be significantly less and integrated team approach that individ- younger adults, CGM may be helpful inexpensive while still achieving similar uals with diabetes assume an active role in these groups. Success correlates with ad-weight loss (46). their care. herence to ongoing use of the device. (C)S16 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 7. Position StatementTable 7dComponents of the comprehensive diabetes evaluation and goals of the patient. SMBG is espe-Medical history cially important for patients treated withc Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding) insulin to monitor for and prevent asymp- tomatic hypoglycemia and hyperglycemia.c Eating patterns, physical activity habits, nutritional status, and weight history; For most patients with type 1 diabetes and growth and development in children and adolescents pregnant women taking insulin, SMBG isc Diabetes education history recommended three or more times daily.c Review of previous treatment regimens and response to therapy (A1C records) For these populations, significantly morec Current treatment of diabetes, including medications and medication adherence, frequent testing may be required to reach meal plan, physical activity patterns, and readiness for behavior change A1C targets safely without hypoglycemiac Results of glucose monitoring and patient’s use of data and for hypoglycemia detection prior toc DKA frequency, severity, and cause critical tasks such as driving. In a largec Hypoglycemic episodes database study of almost 27,000 children and adolescents with type 1 diabetes, after ○ Hypoglycemia awareness adjustment for multiple confounders, in- ○ Any severe hypoglycemia: frequency and cause creased daily frequency of SMBG wasc History of diabetes-related complications significantly associated with lower A1C ○ Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history (20.2% per additional test per day, level- of foot lesions; autonomic, including sexual dysfunction and gastroparesis) ing off at 5 tests per day) and with fewer ○ Macrovascular: CHD, cerebrovascular disease, PAD acute complications (50). The optimal fre- ○ Other: psychosocial problems,* dental disease* quency and timing of SMBG for patientsPhysical examination with type 2 diabetes on noninsulin therapyc Height, weight, BMI is unclear. A meta-analysis of SMBG inc Blood pressure determination, including orthostatic measurements when indicated non–insulin-treated patients with type 2c Fundoscopic examination* diabetes concluded that some regimens ofc Thyroid palpation SMBG were associated with a reduction inc Skin examination (for acanthosis nigricans and insulin injection sites) A1C of 20.4%. However, many of thec Comprehensive foot examination studies in this analysis also included patient education with diet and exercise counsel- ○ Inspection ing and, in some cases, pharmacologic in- ○ Palpation of dorsalis pedis and posterior tibial pulses tervention, making it difficult to assess the ○ Presence/absence of patellar and Achilles reflexes contribution of SMBG alone to improved ○ Determination of proprioception, vibration, and monofilament sensation control (51). Several randomized trialsLaboratory evaluation have called into question the clinical utilityc A1C, if results not available within past 2–3 months and cost-effectiveness of routine SMBG inc If not performed/available within past year: non–insulin-treated patients (52–54). ○ Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides Because the accuracy of SMBG is ○ Liver function tests instrument and user dependent (55), it ○ Test for UAE with spot urine albumin-to-creatinine ratio is important to evaluate each patient’s ○ Serum creatinine and calculated GFR monitoring technique, both initially and ○ Thyroid-stimulating hormone in type 1 diabetes, dyslipidemia, or women over at regular intervals thereafter. In addition, age 50 years optimal use of SMBG requires proper in-Referrals terpretation of the data. Patients should bec Eye care professional for annual dilated eye exam taught how to use the data to adjust foodc Family planning for women of reproductive age intake, exercise, or pharmacological ther-c Registered dietitian for MNT apy to achieve specific glycemic goals,c DMSE and these skills should be reevaluated pe-c Dentist for comprehensive periodontal examination riodically. Real-time CGM through the measure-c Mental health professional, if needed ment of interstitial glucose (which corre-*See appropriate referrals for these categories. lates well with plasma glucose) is available. These sensors require calibration withc CGM may be a supplemental tool to that SMBG is a component of effective SMBG, and the latter are still recommended SMBG in those with hypoglycemia therapy. SMBG allows patients to evaluate for making acute treatment decisions. unawareness and/or frequent hypogly- their individual response to therapy and CGM devices have alarms for hypo- and cemic episodes. (E) assess whether glycemic targets are being hyperglycemic excursions. Small studies achieved. Results of SMBG can be useful in selected patients with type 1 diabetes Major clinical trials of insulin-treated in preventing hypoglycemia and adjusting have suggested that CGM use reduces thepatients that demonstrated the benefits medications (particularly prandial insulin time spent in hypo- and hyperglycemicof intensive glycemic control on diabetes doses), MNT, and physical activity. ranges and may modestly improve glycemiccomplications have included SMBG as part The frequency and timing of SMBG control. A 26-week randomized trial of 322of multifactorial interventions, suggesting should be dictated by the particular needs type 1 patients showed that adults age 25care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S17
  • 8. Position Statementyears and older using intensive insulin diabetes complications (61,62), A1C test- Table 8dCorrelation of A1C with averagetherapy and CGM experienced a 0.5% re- ing should be performed routinely in all glucoseduction in A1C (from ;7.6–7.1%) com- patients with diabetes, at initial assessmentpared with usual intensive insulin therapy and then as part of continuing care. Mea- Mean plasma glucosewith SMBG (56). Sensor use in children, surement approximately every 3 monthsteens, and adults to age 24 years did not determines whether a patient’s glycemic A1C (%) mg/dL mmol/Lresult in significant A1C lowering, and there targets have been reached and maintained. 6 126 7.0was no significant difference in hypoglyce- For any individual patient, the frequency of 7 154 8.6mia in any group. Importantly, the greatest A1C testing should be dependent on the 8 183 10.2predictor of A1C lowering in this study for clinical situation, the treatment regimen 9 212 11.8all age-groups was frequency of sensor use, used, and the judgment of the clinician. 10 240 13.4which was lower in younger age-groups. Some patients with stable glycemia well 11 269 14.9In a smaller RCT of 129 adults and children within target may do well with testing 12 298 16.5with baseline A1C ,7.0%, outcomes com- only twice per year, while unstable or These estimates are based on ADAG data of ;2,700bining A1C and hypoglycemia favored the highly intensively managed patients glucose measurements over 3 months per A1C mea-group utilizing CGM, suggesting that CGM (e.g., pregnant type 1 women) may be surement in 507 adults with type 1, type 2, and nois also beneficial for individuals with type 1 tested more frequently than every 3 diabetes. The correlation between A1C and averagediabetes who have already achieved excel- months. The availability of the A1C result glucose was 0.92 (ref. 67). A calculator for converting A1C results into eAG, in either mg/dL or mmol/L, islent control (57). at the time that the patient is seen (POC available at http://professional.diabetes.org/eAG. A recent RCT of 120 children and testing) has been reported in small studiesadults with type 1 diabetes with baseline to result in increased intensification ofA1C ,7.5% showed that real-time CGM therapy and improvement in glycemic primarily Caucasian type 1 participants inwas associated with reduced time spent in control (63,64). However, two recent sys- the DCCT (68). Clinicians should note thathypoglycemia and a small but significant tematic reviews and meta-analyses found the numbers in the table are now different,decrease in A1C compared with blinded no significant difference in A1C between as they are based on ;2,800 readings perCGM (58). A trial comparing CGM plus POC and laboratory A1C usage (65,66). A1C in the ADAG trial.insulin pump to SMBG plus multiple in- The A1C test is subject to certain In the ADAG study, there were no sig-jections of insulin in adults and children limitations. Conditions that affect eryth- nificant differences among racial and ethnicwith type 1 diabetes showed significantly rocyte turnover (hemolysis, blood loss) groups in the regression lines between A1Cgreater improvements in A1C with “sen- and hemoglobin variants must be consid- and mean glucose, although there was asor augmented pump” therapy (59,60), ered, particularly when the A1C result trend toward a difference between African/but this trial did not isolate the effect of does not correlate with the patient’s clinical African American and Caucasian partici-CGM itself. Although CGM is an evolving situation (55). In addition, A1C does not pants. A small study comparing A1C totechnology, these data suggest that, in ap- provide a measure of glycemic variability or CGM data in type 1 children found apropriately selected patients who are mo- hypoglycemia. For patients prone to glyce- highly statistically significant correlationtivated to wear it most of the time, it may mic variability (especially type 1 patients, between A1C and mean blood glucose,offer benefit. CGM may be particularly or type 2 patients with severe insulin de- although the correlation (r 5 0.7) was sig-useful in those with hypoglycemia un- ficiency), glycemic control is best judged by nificantly lower than in the ADAG trial (69).awareness and/or frequent episodes of hy- the combination of results of SMBG testing Whether there are significant differences inpoglycemia, and studies in this area are and the A1C. The A1C may also serve as a how A1C relates to average glucose in chil-ongoing. CGM forms the underpinning check on the accuracy of the patient’s meter dren or in African American patients is anfor the development of pumps that sus- (or the patient’s reported SMBG results) area for further study. For the time being,pend insulin delivery when hypoglycemia and the adequacy of the SMBG testing the question has not led to different recom-is developing as well as for the burgeoning schedule. mendations about testing A1C or to differ-work on “artificial pancreas” systems. Table 8 contains the correlation be- ent interpretations of the clinical meaning tween A1C levels and mean plasma glucose of given levels of A1C in those populations.b. A1C levels based on data from the international For patients in whom A1C/eAG andRecommendations A1C-Derived Average Glucose (ADAG) tri- measured blood glucose appear discrep-c Perform the A1C test at least two times a al utilizing frequent SMBG and CGM in ant, clinicians should consider the possi- year in patients who are meeting treat- 507 adults (83% Caucasian) with type 1, bilities of hemoglobinopathy or altered ment goals (and who have stable glyce- type 2, and no diabetes (67). ADA and the red cell turnover, and the options of more mic control). (E) American Association of Clinical Chemists frequent and/or different timing of SMBGc Perform the A1C test quarterly in pa- have determined that the correlation (r 5 or use of CGM. Other measures of chronic tients whose therapy has changed or 0.92) is strong enough to justify reporting glycemia such as fructosamine are avail- who are not meeting glycemic goals. (E) both an A1C result and an estimated aver- able, but their linkage to average glucosec Use of point-of-care (POC) testing for age glucose (eAG) result when a clinician and their prognostic significance are not A1C provides the opportunity for more orders the A1C test. The table in pre-2009 as clear as for A1C. timely treatment changes. (E) versions of the “Standards of Medical Care in Diabetes” describing the correlation be- 2. Glycemic goals in adults Because A1C is thought to reflect tween A1C and mean glucose was derived Recommendationsaverage glycemia over several months from relatively sparse data (one 7-point c Lowering A1C to below or around 7%(55), and has strong predictive value for profile over 1 day per A1C reading) in the has been shown to reduce microvascularS18 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 9. Position Statement complications of diabetes, and if im- progression of microvascular complica- events with intensive control, and in 9-year plemented soon after the diagnosis of tions. The Veterans Affairs Diabetes Trial post-DCCT follow-up of the EDIC cohort diabetes is associated with long-term (VADT) showed significant reductions in participants previously randomized to the reduction in macrovascular disease. albuminuria with intensive (achieved me- intensive arm had a significant 42% re- Therefore, a reasonable A1C goal for dian A1C 6.9%) compared with standard duction in CVD outcomes and a significant many nonpregnant adults is ,7%. (B) glycemic control but no difference in reti- 57% reduction in the risk of nonfatalc Providers might reasonably suggest more nopathy and neuropathy (76,77). The Ac- myocardial infarction (MI), stroke, or stringent A1C goals (such as ,6.5%) for tion in Diabetes and Vascular Disease: CVD death compared with those previ- selected individual patients, if this can be Preterax and Diamicron Modified Release ously in the standard arm (82). The benefit achieved without significant hypogly- Controlled Evaluation (ADVANCE) study of intensive glycemic control in this type 1 cemia or other adverse effects of treat- of intensive versus standard glycemic con- cohort has recently been shown to persist ment. Appropriate patients might include trol in type 2 diabetes found a statistically for several decades (83). those with short duration of diabetes, significant reduction in albuminuria, but In type 2 diabetes, there is evidence long life expectancy, and no significant not neuropathy or retinopathy, with an that more-intensive treatment of glycemia CVD. (C) A1C target of ,6.5% (achieved median in newly diagnosed patients may reducec Less-stringent A1C goals (such as ,8%) A1C 6.3%) compared with standard ther- long-term CVD rates. During the UKPDS may be appropriate for patients with a apy achieving a median A1C of 7.0% trial, there was a 16% reduction in cardio- history of severe hypoglycemia, limited (78). Recent analyses from the Action vascular events (combined fatal or nonfatal life expectancy, advanced microvascular to Control Cardiovascular Risk in Diabe- MI and sudden death) in the intensive or macrovascular complications, exten- tes (ACCORD) trial have shown lower glycemic control arm, although this differ- sive comorbid conditions, and those with rates of onset or progression of early- ence was not statistically significant (P 5 longstanding diabetes in whom the stage microvascular complications in 0.052), and there was no suggestion of ben- general goal is difficult to attain despite the intensive glycemic control arm com- efit on other CVD outcomes such as stroke. DSME, appropriate glucose monitoring, pared with the standard arm (79,80). However, after 10 years of follow-up, those and effective doses of multiple glucose- Epidemiological analyses of the DCCT originally randomized to intensive glyce- lowering agents including insulin. (B) and UKPDS (61,62) demonstrate a curvi- mic control had significant long-term re- linear relationship between A1C and mi- ductions in MI (15% with sulfonylurea or Hyperglycemia defines diabetes, and crovascular complications. Such analyses insulin as initial pharmacotherapy, 33%glycemic control is fundamental to the suggest that, on a population level, the with metformin as initial pharmacother-management of diabetes. The DCCT study greatest number of complications will be apy) and in all-cause mortality (13 and(61), a prospective RCT of intensive versus averted by taking patients from very poor 27%, respectively) (75).standard glycemic control in patients with control to fair or good control. These anal- However, results of three more-recentrelatively recently diagnosed type 1 diabe- yses also suggest that further lowering of large trials (ACCORD, ADVANCE, andtes, showed definitively that improved A1C from 7 to 6% is associated with further VADT) suggest no significant reductionglycemic control is associated with signif- reduction in the risk of microvascular com- in CVD outcomes with intensive glycemicicantly decreased rates of microvascular plications, albeit the absolute risk reduc- control in these populations, who had more(retinopathy and nephropathy) and neu- tions become much smaller. Given the advanced diabetes than UKPDS partici-ropathic complications. Follow-up of the substantially increased risk of hypoglyce- pants. All three of these trials were conduc-DCCT cohorts in the Epidemiology of Di- mia (particularly in those with type 1 dia- ted in participants with more-long-standingabetes Interventions and Complications betes, but also in the recent type 2 trials), diabetes (mean duration 8–11 years) and(EDIC) study (70,71) demonstrated persis- the concerning mortality findings in the either known CVD or multiple cardiovas-tence of these microvascular benefits in ACCORD trial (81), and the relatively cular risk factors. Details of these threepreviously intensively treated subjects, much greater effort required to achieve studies are reviewed extensively in aneven though their glycemic control approx- near-normoglycemia, the risks of lower gly- ADA position statement (84).imated that of previous standard arm sub- cemic targets may outweigh the potential The ACCORD study enrolled partic-jects during follow-up. benefits on microvascular complications ipants with either known CVD or two or The Kumamoto Study (72) and U.K. on a population level. However, selected more major CV risk factors and random-Prospective Diabetes Study (UKPDS) individual patients, especially those with ized them to intensive glycemic control(73,74) confirmed that intensive glycemic little comorbidity and long life expectancy (goal A1C ,6%) or standard glycemiccontrol was associated with significantly (who may reap the benefits of further low- control (goal A1C 7–8%). The glycemicdecreased rates of microvascular and neu- ering of glycemia below 7%) may, based on control arm of ACCORD was halted earlyropathic complications in patients with provider judgment and patient preferences, due to the finding of an increased rate oftype 2 diabetes. Long-term follow-up of adopt more-intensive glycemic targets (for mortality in the intensive arm comparedthe UKPDS cohorts showed persistence of example, an A1C target ,6.5%) as long with the standard arm (1.41 vs. 1.14% perthe effect of early glycemic control on as significant hypoglycemia does not year; HR 1.22, 95% CI 1.01–1.46), with amost microvascular complications (75). become a barrier. similar increase in cardiovascular deaths. Subsequent trials in patients with CVD, a more common cause of death This increase in mortality in the intensivemore-long-standing type 2 diabetes, de- in populations with diabetes than micro- glycemic control arm was seen in all pre-signed primarily to look at the role of vascular complications, is less clearly im- specified patient subgroups. The primaryintensive glycemic control on cardiovas- pacted by levels of hyperglycemia or outcome of ACCORD (MI, stroke, or car-cular outcomes, also confirmed a bene- intensity of glycemic control. In the DCCT, diovascular death) was nonsignificantlyfit, although more modest, on onset or there was a trend toward lower risk of CVD lower in the intensive glycemic controlcare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S19
  • 10. Position Statementgroup, due to a reduction in nonfatal MI, insulin or maximal-dose oral agents as those with very long duration of diabe-both when the glycemic control interven- (median entry A1C 9.4%) to a strategy tes, known history of severe hypoglycemia,tion was halted (81) and at completion of of intensive glycemic control (goal A1C advanced atherosclerosis, and advancedthe planned follow-up (85). ,6.0%) or standard glycemic control, age/ frailty. Certainly, providers should be Exploratory analyses of the mortality with a planned A1C separation of at least vigilant in preventing severe hypoglycemiafindings of ACCORD (evaluating variables 1.5%. The primary outcome of VADT in patients with advanced disease andincluding weight gain, use of any specific was a composite of CVD events. The cu- should not aggressively attempt to achievedrug or drug combination, and hypogly- mulative primary outcome was nonsig- near-normal A1C levels in patients incemia) were reportedly unable to identify a nificantly lower in the intensive arm whom such a target cannot be reasonablyclear explanation for the excess mortality in (76). An ancillary study of VADT demon- easily and safely achieved. Severe or fre-the intensive arm (81). The ACCORD in- strated that intensive glycemic control quent hypoglycemia is an absolute indica-vestigators subsequently published addi- was quite effective in reducing CVD tion for the modification of treatmenttional epidemiologic analyses showing no events in individuals with less atheroscle- regimens, including setting higher glyce-increase in mortality in either the intensive rosis at baseline (assessed by coronary mic goals. Many factors, including patientarm participants who achieved A1C levels calcium) but not in those with more ex- preferences, should be taken into account,7% or those who lowered their A1C tensive baseline atherosclerosis (88). when developing a patient’s individualizedquickly after trial enrollment. In fact, al- The evidence for a cardiovascular goals (79).though there was no A1C level at which benefit of intensive glycemic control pri- Recommended glycemic goals forintensive arm participants had significantly marily rests on long-term follow-up of many nonpregnant adults are shown inlower mortality than standard arm partici- study cohorts treated early in the course Table 9. The recommendations are basedpants, the highest risk for mortality was of type 1 and type 2 diabetes and subset on those for A1C values, with listed bloodobserved in intensive arm participants analyses of ACCORD, ADVANCE, and glucose levels that appear to correlate withwith the highest A1C levels (86). VADT. A recent group-level meta-analysis achievement of an A1C of ,7%. The issue The role of hypoglycemia in the ex- of the latter three trials suggests that of pre- versus postprandial SMBG targets iscess mortality findings was also complex. glucose lowering has a modest (9%) but complex (90). Elevated postchallenge (2-hSevere hypoglycemia was significantly statistically significant reduction in major OGTT) glucose values have been associatedmore likely in participants randomized CVD outcomes, primarily nonfatal MI, with increased cardiovascular risk indepen-to the intensive glycemic control arm. with no significant effect on mortality. dent of FPG in some epidemiological stud-However, excess mortality in the intensive However, heterogeneity of the mortality ies. In diabetic subjects, some surrogateversus standard arms was only significant effects across studies was noted, precluding measures of vascular pathology, such as en-for participants with no severe hypoglyce- firm summary measures of the mortality dothelial dysfunction, are negatively af-mia, and not for those with one or more effects. A prespecified subgroup analysis fected by postprandial hyperglycemiaepisodes. Severe hypoglycemia was associ- suggested that major CVD outcome reduc- (91). It is clear that postprandial hypergly-ated with excess mortality in either arm, tion occurred in patients without known cemia, like preprandial hyperglycemia,but the association was stronger in those CVD at baseline (HR 0.84, 95% CI 0.74– contributes to elevated A1C levels, withrandomized to the standard glycemic con- 0.94) (89). Conversely, the mortality find- its relative contribution being higher attrol arm (87). Unlike the case with the ings in ACCORD and subgroup analyses of A1C levels that are closer to 7%. However,DCCT, where lower achieved A1C levels VADT suggest that the potential risks of outcome studies have clearly shown A1Cwere related to significantly increased rates very intensive glycemic control may out- to be the primary predictor of complica-of severe hypoglycemia, in ACCORD every weigh its benefits in some patients, such tions, and landmark glycemic control trials1% decline in A1C from baseline to 4months into the trial was associatedwith a significant decrease in the rate of Table 9dSummary of glycemic recommendations for many nonpregnant adultssevere hypoglycemia in both arms (86). with diabetes The primary outcome of ADVANCEwas a combination of microvascular events A1C ,7.0%*(nephropathy and retinopathy) and major Preprandial capillary plasma glucose 70–130 mg/dL* (3.9–7.2 mmol/L)adverse cardiovascular events (MI, stroke, Peak postprandial capillary plasma glucose† ,180 mg/dL* (,10.0 mmol/L)and cardiovascular death). Intensive glyce- c Goals should be individualized based on*mic control (to a goal A1C ,6.5% vs. treat- ○ duration of diabetesment to local standards) significantly ○ age/life expectancyreduced the primary end point. However, ○ comorbid conditionsthis was due to a significant reduction in ○ known CVD or advanced microvascularthe microvascular outcome, primarily de- complicationsvelopment of macroalbuminuria, with no ○ hypoglycemia unawarenesssignificant reduction in the macrovascular ○ individual patient considerationsoutcome. There was no difference in overall c More- or less-stringent glycemic goals may beor cardiovascular mortality between the in- appropriate for individual patientstensive compared with the standard glyce- c Postprandial glucose may be targeted if A1C goals aremic control arms (78). not met despite reaching preprandial glucose goals VADT randomized participants with †Postprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peaktype 2 diabetes who were uncontrolled on levels in patients with diabetes.S20 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 11. Position Statementsuch as the DCCT and UKPDS relied over- hypoglycemia with equal A1C-lowering to safely achieve and maintain glycemicwhelmingly on preprandial SMBG. Addi- in type 1 diabetes (95,96). control and to change interventions whentionally, an RCT in patients with known Therefore, recommended therapy for therapeutic goals are not being met.CVD found no CVD benefit of insulin regi- type 1 diabetes consists of the following ADA and EASD have partnered onmens targeting postprandial glucose com- components: 1) use of multiple-dose in- new guidance for individualization of usepared with those targeting preprandial sulin injections (three to four injections of medication classes and combinationsglucose (92). For individuals who have pre- per day of basal and prandial insulin) or in patients with type 2 diabetes. Thesemeal glucose values within target but who CSII therapy; 2) matching prandial insu- guidelines, to be published in early 2012,have A1C values above target, monitoring lin to carbohydrate intake, premeal blood will be less prescriptive than prior algo-postprandial plasma glucose (PPG) 1–2 h glucose, and anticipated activity; and 3) rithms, and will discuss advantages andafter the start of the meal and treatment for many patients (especially if hypogly- disadvantages of the available medicationaimed at reducing PPG values to ,180 cemia is a problem), use of insulin ana- classes as well as considerations for theirmg/dL may help lower A1C and is a reason- logs. There are excellent reviews available use. For information about currently ap-able recommendation for postprandial test- that guide the initiation and management proved classes of medications for treat-ing and targets. Glycemic goals for children of insulin therapy to achieve desired gly- ing hyperglycemia in type 2 diabetes, seeare provided in section VII.A.1.a. Glycemic cemic goals (3,95,97). Table 10.Control. Because of the increased frequency of As regards goals for glycemic control other autoimmune diseases in type 1 di- E. Medical nutrition therapy (MNT)for women with GDM, recommendations abetes, screening for thyroid dysfunction, General recommendationsfrom the Fifth International Workshop- vitamin B12 deficiency, or celiac disease c Individuals who have prediabetes orConference on Gestational Diabetes (93) should be considered based on signs and diabetes should receive individualizedare to target maternal capillary glucose symptoms. Periodic screening in absence MNT as needed to achieve treatmentconcentrations of: of symptoms has been recommended, but goals, preferably provided by a regis- the effectiveness and optimal frequency are tered dietitian familiar with the compo-c preprandial: #95 mg/dL (5.3 mmol/L), unclear. nents of diabetes MNT. (A) and either: c Because MNT can result in cost-savingsc 1-h postmeal: #140 mg/dL (7.8 mmol/L) 2. Therapy for type 2 diabetes and improved outcomes (B), MNT should or Recommendations be adequately covered by insurance andc 2-h postmeal: #120 mg/dL (6.7 mmol/L) c At the time of type 2 diabetes diagnosis, other payers. (E) initiate metformin therapy along with Energy balance, overweight, and obesity For women with preexisting type 1 or lifestyle interventions, unless metfor- c Weight loss is recommended for alltype 2 diabetes who become pregnant, a min is contraindicated. (A) overweight or obese individuals whorecent consensus statement (94) recom- c In newly diagnosed type 2 diabetic pa- have or are at risk for diabetes. (A)mended the following as optimal glycemic tients with markedly symptomatic and/ c For weight loss, either low-carbohydrate,goals, if they can be achieved without ex- or elevated blood glucose levels or A1C, low-fat calorie-restricted, or Mediterra-cessive hypoglycemia: consider insulin therapy, with or with- nean diets may be effective in the short- out additional agents, from the outset. (E) term (up to 2 years). (A)c premeal, bedtime, and overnight glucose c If noninsulin monotherapy at maximal c For patients on low-carbohydrate diets, 60–99 mg/dL (3.3–5.4 mmol/L) tolerated dose does not achieve or main- monitor lipid profiles, renal function,c peak postprandial glucose 100–129 tain the A1C target over 3–6 months, and protein intake (in those with ne- mg/dL (5.4–7.1 mmol/L) add a second oral agent, a GLP-1 receptor phropathy), and adjust hypoglycemicc A1C ,6.0% agonist, or insulin. (E) therapy as needed. (E) c Physical activity and behavior modifi-D. Pharmacologic and overall Prior expert consensus statements cation are important components ofapproaches to treatment have suggested approaches to manage- weight loss programs and are most helpful1. Therapy for type 1 diabetes. The ment of hyperglycemia in individuals in maintenance of weight loss. (B)DCCT clearly showed that intensive in- with type 2 diabetes (98). Highlights in- Recommendations for primary preventionsulin therapy (three or more injections per clude intervention at the time of diagnosis of diabetesday of insulin, continuous subcutaneous with metformin in combination with life- c Among individuals at high risk for de-insulin infusion [CSII], or insulin pump style changes (MNT and exercise) and con- veloping type 2 diabetes, structuredtherapy) was a key part of improved tinuing timely augmentation of therapy programs that emphasize lifestyle changesglycemia and better outcomes (61,82). At with additional agents (including early ini- that include moderate weight loss (7%the time of the study, therapy was carried tiation of insulin therapy) as a means of body weight) and regular physical ac-out with short- and intermediate-acting hu- achieving and maintaining recommended tivity (150 min/week), with dietaryman insulins. Despite better microvascular levels of glycemic control (i.e., A1C ,7% strategies including reduced calories andoutcomes, intensive insulin therapy was as- for most patients). As A1C targets are not reduced intake of dietary fat, can reducesociated with a high rate in severe hypogly- achieved, treatment intensification is based the risk for developing diabetes and arecemia (62 episodes per 100 patient-years of on the addition of another agent from a therefore recommended. (A)therapy). Since the time of the DCCT, a different class. Meta-analyses (99) suggest c Individuals at risk for type 2 diabetesnumber of rapid-acting and long-acting that overall, each new class of noninsulin should be encouraged to achieve theinsulin analogs have been developed. agents added to initial therapy lowers A1C U.S. Department of Agriculture (USDA)These analogs are associated with less around 0.9–1.1%. The overall objective is recommendation for dietary fiber (14 gcare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S21
  • 12. Table 10dNoninsulin therapies for hyperglycemia in type 2 diabetes: properties of selected glucose-lowering drugs that may guide individualization of therapyS22 Class Compound(s) Mechanism Action(s) Advantages Disadvantages Cost Biguanides Metformin Activates AMP-kinase c Hepatic glucose c No weight gain c Gastrointestinal side effects Low production ↓ c No hypoglycemia (diarrhea, abdominal Position Statement c Intestinal glucose c Reduction in cramping) absorption ↓ c Lactic acidosis (rare) cardiovascular c Insulin action ↑ events and c Vitamin B12 deficiency mortality c Contraindications: reduced (UKPDS f/u) kidney function Sulfonylureas c Glibenclamide/ Closes KATP c ↑ Insulin secretion c Generally well c Relatively glucose-independent Low (2nd generation) Glyburide channels on b-cell tolerated stimulation of insulin secretion: c Glipizide plasma membranes c Reduction in Hypoglycemia, including c Gliclazide cardiovascular episodes necessitating hospital c Glimepiride events and admission and causing death mortality c Weight gain (UKPDS f/u) c May blunt myocardial ischemicDIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 preconditioning c Low “durability” Meglitinides c Repaglinide Closes KATP Insulin secretion ↑ Accentuated effects c Hypoglycemia, weight gain, Medium c Nateglinide channels on b-cell around meal c May blunt myocardial ischemic plasma membranes ingestion preconditioning c Dosing frequency Thiazolidinediones c Pioglitazone Activates the nuclear c Peripheral insulin c No hypoglycemia c Weight gain High (Glitazones) transcription sensitivity ↑ c HDL cholesterol ↑ c Edema factor PPAR-g c Triglycerides ↓ c Heart failure c Bone fractures c Rosiglitazone As above As above No hypoglycemia c LDL cholesterol ↑ High c Weight gain c Edema c Heart failure c Bone fractures c Increased cardiovascular events (mixed evidence) c FDA warnings on cardiovascular safety c Contraindicated in patients with heart disease a-Glucosidase c Acarbose Inhibits intestinal Intestinal carbohydrate c Nonsystemic c Gastrointestinal side effects (gas, Medium inhibitors c Miglitol a-glucosidase digestion (and, medication flatulence, diarrhea) consecutively, c Postprandial c Dosing frequency absorption) slowedcare.diabetesjournals.org glucose ↓
  • 13. Position Statement fiber/1,000 kcal) and foods containing Medium Cost whole grains (one-half of grain intake). High High High (B) c Individuals at risk for type 2 diabetes should be encouraged to limit their in- take of sugar-sweetened beverages. (B) thyroid tumors in animals (liraglutide) Gastrointestinal side effects (nausea, Cases of acute pancreatitis observed Recommendations for management of Occasional reports of urticaria/ Cases of pancreatitis observed May interfere with absorption diabetes C-cell hyperplasia/ medullary Long-term safety unknown Long-term safety unknown Long-term safety unknown Disadvantages Macronutrients in diabetes management c The mix of carbohydrate, protein, and of other medications vomiting, diarrhea) fat may be adjusted to meet the meta- Dizziness/syncope bolic goals and individual preferences Triglycerides ↑ Constipation of the person with diabetes. (C) angioedema c Monitoring carbohydrate, whether by Injectable Rhinitis Fatigue Nausea carbohydrate counting, choices, or ex- perience-based estimation, remains a key strategy in achieving glycemic control. (B) c c c c c c c c c c c c c c c c c Saturated fat intake should be ,7% of total calories. (B) Weight “neutrality” c Reducing intake of trans fat lowers LDL LDL cholesterol ↓ Weight reduction No hypoglycemia No hypoglycemia improved b-cell No hypoglycemia cholesterol and increases HDL choles- Advantages mass/function Potential for terol (A), therefore intake of trans fat should be minimized. (E) Other nutrition recommendations c If adults with diabetes choose to use alcohol, they should limit intake to a c c c c c c moderate amount (one drink per day or less for adult women and two drinks per regulation of metabolism Adapted with permission from Silvio Inzucchi, Yale University. PPAR, peroxisome proliferator–activated receptor. Slows gastric emptying day or less for adult men) and should Glucagon secretion ↓ Glucagon secretion ↓ (glucose-dependent) (glucose-dependent) Alters hypothalamic Insulin sensitivity ↑ take extra precautions to prevent hypo- Insulin secretion ↑ Insulin secretion ↑ glycemia. (E) Action(s) concentration ↑ concentration ↑ c Routine supplementation with anti- Active GLP-1 Active GIP oxidants, such as vitamins E and C and Unknown Satiety ↑ carotene, is not advised because of lack of evidence of efficacy and concern re- lated to long-term safety. (A) c c c c c c c c c c c c It is recommended that individualized meal planning include optimization of Activates dopaminergic Inhibits DPP-4 activity, endogenously released food choices to meet recommended endocrine pancreas; prolongs survival of daily allowance (RDA)/dietary reference brain/autonomous incretin hormones receptors (b-cells/ Mechanism nervous system) Binds bile acids/ intake (DRI) for all micronutrients. (E) Activates GLP-1 cholesterol MNT is an integral component of receptors diabetes prevention, management, and self-management education. In addition to its role in preventing and controlling diabetes, ADA recognizes the importance of nutrition as an essential component of Compound(s) Bromocriptine an overall healthy lifestyle. A full review of Vildagliptin Saxagliptin Linagliptin Liraglutide Colesevelam Sitagliptin Exenatide the evidence regarding nutrition in pre- venting and controlling diabetes and its complications and additional nutrition- related recommendations can be found in c c c c c c the ADA position statement “Nutrition Table 10dContinued Recommendations and Interventions for Diabetes,” published in 2007 and updated DPP-4 inhibitors GLP-1 receptor sequestrants in 2008 (100). Achieving nutrition-related enhancers) Dopamine-2 mimetics) goals requires a coordinated team effort (incretin (incretin agonists agonists Bile acid that includes the active involvement of Class the person with prediabetes or diabetes. Because of the complexity of nutritioncare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S23
  • 14. Position Statementissues, it is recommended that a registered of sugar-sweetened beverages have coin- Although brain fuel needs can be met ondietitian who is knowledgeable and skilled cided with the epidemics of obesity and lower-carbohydrate diets, long-term meta-in implementing nutrition therapy into di- type 2 diabetes. In a meta-analysis of eight bolic effects of very-low-carbohydrateabetes management and education be the prospective cohort studies (N 5 310,819), a diets are unclear, and such diets eliminateteam member who provides MNT. diet high in consumption of sugar-sweetened many foods that are important sources of Clinical trials/outcome studies of beverages was associated with the devel- energy, fiber, vitamins, and minerals andMNT have reported decreases in A1C at opment of type 2 diabetes (n 5 15,043). that are important in dietary palatability3–6 months ranging from 0.25 to 2.9% Individuals in the highest versus the low- (129).with higher reductions seen in type 2 di- est quantile of sugar-sweetened beverage Saturated and trans fatty acids are theabetes of shorter duration. Multiple studies intake had a 26% greater risk of develop- principal dietary determinants of plasmahave demonstrated sustained improve- ing diabetes (119). LDL cholesterol. There is a lack of evidencements in A1C at 12 months and longer For individuals with type 2 diabetes, on the effects of specific fatty acids on peo-when an registered dietitian provided studies have demonstrated that moderate ple with diabetes; the recommended goalsfollow-up visits ranging from monthly to weight loss (5% of body weight) is asso- are therefore consistent with those for indi-three sessions per year (101–108). Studies ciated with decreased insulin resistance, viduals with CVD (109,130).in nondiabetic suggest that MNT reduces improved measures of glycemia and lipe-LDL cholesterol by 15–25 mg/dL up to mia, and reduced blood pressure (120); Reimbursement for MNT16% (109) and support a role for life- longer-term studies ($52 weeks) showed MNT, when delivered by a registeredstyle modification in treating hypertension mixed effects on A1C in adults with type 2 dietitian according to nutrition practice(109,110). diabetes (121–123), and in some studies guidelines, is reimbursed as part of the While the importance of weight loss results were confounded by pharmaco- Medicare program as overseen by thefor overweight and obese individuals is logic weight loss therapy. Look AHEAD Centers for Medicare and Medicaid Serv-well documented, an optimal macronu- (Action for Health in Diabetes) is a large ices (CMS) (www.cms.gov).trient distribution and dietary pattern of clinical trial designed to determine whetherweight loss diets has not been established. long-term weight loss will improve glyce- F. Diabetes self-managementA systematic review of 80 weight loss mia and prevent cardiovascular events in education (DSME)studies of $1 year duration demonstrated subjects with type 2 diabetes. One-year re- Recommendationsthat moderate weight loss achieved through sults of the intensive lifestyle intervention c People with diabetes should receivediet alone, diet and exercise, and meal re- in this trial show an average 8.6% weight DSME according to national standardsplacements can be achieved and main- loss, significant reduction of A1C, and re- and diabetes self-management supporttained (4.8–8% weight loss at 12 months) duction in several CVD risk factors (124), when their diabetes is diagnosed and as(111). Both low-fat low-carbohydrate and with benefits sustained at 4 years (125). needed thereafter. (B)Mediterranean style eating patterns have When completed, the Look AHEAD trial c Effective self-management and qualitybeen shown to promote weight loss with should provide insight into the effects of of life are the key outcomes of DSMEsimilar results after 1 to 2 years of follow-up long-term weight loss on important clinical and should be measured and monitored(112–115). A meta-analysis showed that outcomes. as part of care. (C)at 6 months, low-carbohydrate diets were Although numerous studies have at- c DSME should address psychosocialassociated with greater improvements in tempted to identify the optimal mix of issues, since emotional well-being istriglyceride and HDL cholesterol concen- macronutrients for meal plans of people associated with positive diabetes out-trations than low-fat diets; however, LDL with diabetes, it is unlikely that one such comes. (C)cholesterol was significantly higher on the combination of macronutrients exists. The c Because DSME can result in cost-savingslow-carbohydrate diets (116). best mix of carbohydrate, protein, and fat and improved outcomes (B), DSME Because of the effects of obesity on appears to vary depending on individual should be adequately reimbursed byinsulin resistance, weight loss is an impor- circumstances. It must be clearly recog- third-party payers. (E)tant therapeutic objective for overweight or nized that regardless of the macronutrientobese individuals who are at risk for di- mix, total caloric intake must be appropri- DSME is an essential element of di-abetes (117). The multifactorial intensive ate to weight management goal. Further, abetes care (131–136), and nationallifestyle intervention employed in the individualization of the macronutrient standards for DSME (137) are based onDPP, which included reduced intake of composition will depend on the metabolic evidence for its benefits. Education helpsfat and calories, led to weight loss averaging status of the patient (e.g., lipid profile, renal people with diabetes initiate effective self-7% at 6 months and maintenance of function) and/or food preferences. A management and cope with diabetes when5% weight loss at 3 years, associated variety of dietary meal patterns are likely they are first diagnosed. Ongoing DSMEwith a 58% reduction in incidence of effective in managing diabetes including and diabetes self-management supporttype 2 diabetes (20). A RCT looking at Mediterranean-style, plant-based (vegan or (DSMS) also help people with diabeteshigh-risk individuals in Spain showed the vegetarian), low-fat and lower-carbohydrate maintain effective self-managementMediterranean dietary pattern reduced the eating patterns (113,126–128). throughout a lifetime of diabetes as theyincidence of diabetes in the absence of It should be noted that the RDA for face new challenges and as treatment ad-weight loss by 52% compared with the digestible carbohydrate is 130 g/day and vances become available. DSME helps pa-low-fat diet control group (118). is based on providing adequate glucose as tients optimize metabolic control, prevent Although our society abounds with the required fuel for the central nervous and manage complications, and maximizeexamples of high-calorie nutrient-poor system without reliance on glucose pro- quality of life in a cost-effective mannerfoods, large increases in the consumption duction from ingested protein or fat. (138).S24 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 15. Position Statement DSME and DSMS are the on-going recommendations, particularly among adults over age 18 years perform 150 minprocesses of facilitating the knowledge, the Medicare population, and have lower per week of moderate-intensity or 75 minskill, and ability necessary for diabetes Medicare and commercial claim costs per week of vigorous aerobic physical activ-self-care. This process incorporates the (166,167). ity or an equivalent combination of the two.needs, goals, and life experiences of the National standards for DSME. The In addition, the guidelines suggest thatperson with diabetes. The overall objec- national standards for DSME are designed adults also perform muscle-strengtheningtives of DSME and DSMS are to support to define quality DSME and to assist activities that involve all major muscleinformed decision-making, self-care be- diabetes educators in a variety of settings groups 2 or more days per week. The guide-haviors, problem-solving, and active col- to provide evidence-based education lines suggest that adults over age 65 years,laboration with the health care team to (137). The standards, currently being up- or those with disabilities, follow the adultimprove clinical outcomes, health status, dated, are reviewed and updated every guidelines if possible or (if this is not pos-and quality of life in a cost-effective man- 5 years by a task force representing key sible) be as physically active as they are able.ner (137). organizations involved in the field of di- Studies included in a meta-analysis of the Current best practice for DSME is a abetes education and care. effects of exercise interventions on glycemicskills-based approach that focuses on Reimbursement for DSME. DSME, control (168) had a mean number of ses-helping those with diabetes make in- when provided by a program that meets sions per week of 3.4, with a mean durationformed self-management choices. DSME national standards for DSME and is recog- of 49 min per session. The DPP lifestyle in-has changed from a didactic approach nized by ADA or other approval bodies, is tervention, which included 150 min perfocusing on providing information to reimbursed as part of the Medicare program week of moderate-intensity exercise, had amore theoretically based empowerment as overseen by the Centers for Medicare and beneficial effect on glycemia in those withmodels that focus on helping those with Medicaid Services (CMS) (www.cms.gov). prediabetes. Therefore, it seems reasonablediabetes make informed self-management DSME is also covered by most health insur- to recommend that people with diabetes trydecisions. Care of diabetes has shifted to an ance plans. to follow the physical activity guidelines forapproach that is more patient centered and the general population.places the person with diabetes and his or G. Physical activity Progressive resistance exercise im-her family at the center of the care model Recommendations proves insulin sensitivity in older menworking in collaboration with health care c People with diabetes should be advised with type 2 diabetes to the same or even aprofessionals. Patient-centered care is re- to perform at least 150 min/week of greater extent as aerobic exercise (172).spectful of and responsive to individual moderate-intensity aerobic physical Clinical trials have provided strong evi-patient preferences, needs, and values and activity (50–70% of maximum heart dence for the A1C lowering value of resis-ensures that patient’s values guide all deci- rate), spread over at least 3 days per tance training in older adults with type 2sion making (139). week with no more than 2 consecutive diabetes (173,174), and for an additiveEvidence for the benefits of DSME. Mul- days without exercise. (A) benefit of combined aerobic and resistancetiple studies have found that DSME is c In the absence of contraindications, exercise in adults with type 2 diabetesassociated with improved diabetes knowl- people with type 2 diabetes should be (175,176). In the absence of contraindica-edge and self-care behavior (131), improved encouraged to perform resistance train- tions, patients with type 2 diabetes shouldclinical outcomes such as lower A1C ing at least twice per week. (A) be encouraged to do at least two weekly(132,133,135,136,140,141), lower self- sessions of resistance exercise (exercisereported weight (131), improved quality Exercise is an important part of the with free weights or weight machines),of life (134,141,142), healthy coping diabetes management plan. Regular exer- with each session consisting of at least(143), and lower costs (144). Better out- cise has been shown to improve blood one set of five or more different resistancecomes were reported for DSME inter- glucose control, reduce cardiovascular risk exercises involving the large muscle groupsventions that were longer and included factors, contribute to weight loss, and (170).follow-up support (DSMS) (131,145–149) improve well-being. Furthermore, regular Evaluation of the diabetic patient before(150), that were culturally (151,152) and exercise may prevent type 2 diabetes in recommending an exercise program.age appropriate (153,154), that were tai- high-risk individuals (20–22). Structured Prior guidelines suggested that beforelored to individual needs and prefer- exercise interventions of at least 8-week recommending a program of physicalences, and that addressed psychosocial duration have been shown to lower A1C activity, the provider should assess pa-issues and incorporated behavioral strat- by an average of 0.66% in people with tients with multiple cardiovascular riskegies (131,135,155–157). Both individual type 2 diabetes, even with no significant factors for coronary artery disease (CAD).and group approaches have been found change in BMI (168). Higher levels of ex- As discussed more fully in section VI.A.5.effective (158–161). There is growing evi- ercise intensity are associated with CHD Screening and Treatment, the area ofdence for the role of community health greater improvements in A1C and in fit- screening asymptomatic diabetic patientsworkers and peer (162,163) and lay leaders ness (169). A joint position statement by for CAD remains unclear, and a recent ADA(164) in delivering DSME and support in ADA and the American College of Sports consensus statement on this issue con-addition to the core team (165). Medicine summarizes the evidence for ben- cluded that routine screening is not rec- Diabetes education is associated with efits of exercise in people with type 2 diabe- ommended (177). Providers should useincreased use of primary and preventive tes (170). clinical judgment in this area. Certainly,services and lower use of acute, inpatient Frequency and type of exercise. high-risk patients should be encouragedhospital services (144). Patients who par- The U.S. Department of Health and Hu- to start with short periods of low-inten-ticipate in diabetes education are more man Services’ “Physical Activity Guide- sity exercise and increase the intensitylikely to follow best practice treatment lines for Americans” (171) suggests that and duration slowly.care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S25
  • 16. Position Statement Providers should assess patients for Autonomic neuropathy. health, and no intervention characteris-conditions that might contraindicate certain Autonomic neuropathy can increase the tics predicted benefit on both outcomes,types of exercise or predispose to injury, risk of exercise-induced injury or ad- was shown (189).such as uncontrolled hypertension, se- verse event through decreased cardiac Key opportunities for screening ofvere autonomic neuropathy, severe pe- responsiveness to exercise, postural hy- psychosocial status occur at diagnosis,ripheral neuropathy or history of foot potension, impaired thermoregulation, during regularly scheduled managementlesions, and unstable proliferative reti- impaired night vision due to impaired visits, during hospitalizations, at discoverynopathy. The patient’s age and previous papillary reaction, and unpredictable car- of complications, or when problems withphysical activity level should be consid- bohydrate delivery from gastroparesis pre- glucose control, quality of life, or adherenceered. disposing to hypoglycemia (181). are identified. Patients are likely to exhibitExercise in the presence of nonoptimal Autonomic neuropathy is also strongly as- psychological vulnerability at diagnosisglycemic control hyperglycemia. When sociated with CVD in people with diabetes and when their medical status changes,people with type 1 diabetes are deprived (182,183). People with diabetic auto- e.g., the end of the honeymoon period,of insulin for 12–48 h and are ketotic, nomic neuropathy should undergo car- when the need for intensified treatment isexercise can worsen hyperglycemia and diac investigation before beginning evident, and when complications are dis-ketosis (178); therefore, vigorous activity physical activity that is more intense covered (187).should be avoided in the presence of ke- than that to which they are accustomed. Issues known to impact self-managementtosis. However, it is not necessary to Albuminuria and nephropathy. and health outcomes include but are notpostpone exercise based simply on hy- Physical activity can acutely increase uri- limited to attitudes about the illness,perglycemia, provided the patient feels nary protein excretion. However, there is expectations for medical managementwell and urine and/or blood ketones are no evidence that vigorous exercise increa- and outcomes, affect/mood, general andnegative. ses the rate of progression of diabetic diabetes-related quality of life, diabetes-Hypoglycemia. In individuals taking in- kidney disease, and there is likely no need related distress (190,191), resources (fi-sulin and/or insulin secretagogues, phys- for any specific exercise restrictions for nancial, social, and emotional) (192), andical activity can cause hypoglycemia if people with diabetic kidney disease psychiatric history (193–195). Screeningmedication dose or carbohydrate con- (184). tools are available for a number of thesesumption is not altered. For individuals areas (156). Indications for referral to aon these therapies, added carbohydrate H. Psychosocial assessment and care mental health specialist familiar with diabe-should be ingested if preexercise glucose Recommendations tes management may include gross non- c It is reasonable to include assessment of compliance with medical regimen (by selflevels are ,100 mg/dL (5.6 mmol/L).Hypoglycemia is rare in diabetic individ- the patient’s psychological and social or others) (195), depression with the pos-uals who are not treated with insulin or situation as an ongoing part of the sibility of self-harm, debilitating anxietyinsulin secretagogues, and no preventive medical management of diabetes. (E) (alone or with depression), indications of c Psychosocial screening and follow-up an eating disorder (196), or cognitive func-measures for hypoglycemia are usuallyadvised in these cases. may include, but is not limited to, atti- tioning that significantly impairs judgment. tudes about the illness, expectations for It is preferable to incorporate psychologicalExercise in the presence of specific medical management and outcomes, assessment and treatment into routine carelong-term complications of diabetes affect/mood, general and diabetes- rather than waiting for identification of aretinopathy. In the presence of prolifer- related quality of life, resources (financial, specific problem or deterioration in psy-ative diabetic retinopathy (PDR) or severe social, and emotional), and psychiatric chological status (156). Although the cli-nonproliferative diabetic retinopathy history. (E) nician may not feel qualified to treat(NPDR), vigorous aerobic or resistance c Consider screening for psychosocial psychological problems, utilizing theexercise may be contraindicated because problems such as depression and patient-provider relationship as a foun-of the risk of triggering vitreous hemor- diabetes-related distress, anxiety, eat- dation for further treatment can increaserhage or retinal detachment (179). ing disorders, and cognitive impairment the likelihood that the patient will acceptPeripheral neuropathy. Decreased pain when self-management is poor. (C) referral for other services. It is importantsensation in the extremities results in to establish that emotional well-being isincreased risk of skin breakdown and Psychological and social problems part of diabetes management.infection and of Charcot joint destruction. can impair the individual’s (185–188) orPrior recommendations have advised non– family’s ability to carry out diabetes care I. When treatment goals are not metweight-bearing exercise for patients with tasks and therefore compromise health For a variety of reasons, some people withsevere peripheral neuropathy. However, status. There are opportunities for the cli- diabetes and their health care providersstudies have shown that moderate-intensity nician to assess psychosocial status in a do not achieve the desired goals of treat-walking may not lead to increased risk of timely and efficient manner so that re- ment (Table 9). Rethinking the treatmentfoot ulcers or reulceration in those with ferral for appropriate services can be regimen may require assessment of barriersperipheral neuropathy (180). All indi- accomplished. A systematic review and including income, health literacy, diabetesviduals with peripheral neuropathy meta-analysis showed that psychosocial distress, depression, and competing de-should wear proper footwear and exam- interventions modestly but significantly mands, including those related to familyine their feet daily to detect lesions early. improved A1C (standardized mean responsibilities and dynamics. Other strat-Anyone with a foot injury or open sore difference 20.29%) and mental health egies may include culturally appropriateshould be restricted to non–weight- outcomes. However, a limited association and enhanced DSME, co-managementbearing activities. between the effects on A1C and mental with a diabetes team, referral to a medicalS26 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 17. Position Statementsocial worker for assistance with insurance c Glucagon should be prescribed for all taken to ensure that unexpired glucagoncoverage, or change in pharmacological individuals at significant risk of severe kits are available.therapy. Initiation of or increase in SMBG, hypoglycemia, and caregivers or family Prevention of hypoglycemia is a crit-utilization of continuous glucose monitor- members of these individuals instructed ical component of diabetes management.ing, frequent contact with the patient, or in its administration. Glucagon admin- Patients should understand situationsreferral to a mental health professional or istration is not limited to health care that increase their risk of hypoglycemia,physician with special expertise in diabetes professionals. (E) such as when fasting for tests or proce-may be useful. Providing patients with an c Individuals with hypoglycemia un- dures, during or after intense exercise, andalgorithm for self-titration of insulin doses awareness or one or more episodes of during sleep; and that increase the risk ofbased on SMBG results may be helpful for severe hypoglycemia should be advised harm to self or others from hypoglycemia,type 2 patients who take insulin (197). to raise their glycemic targets to strictly such as with driving. Teaching people with avoid further hypoglycemia for at least diabetes to balance insulin use, carbohy- several weeks, to partially reverse hypo- drate intake, and exercise is a necessary butJ. Intercurrent illness glycemia unawareness and reduce risk of not always sufficient strategy for preven-The stress of illness, trauma, and/or surgery future episodes. (B) tion. In type 1 diabetes and severelyfrequently aggravates glycemic control and insulin-deficient type 2 diabetes, the syn-may precipitate diabetic ketoacidosis Hypoglycemia is the leading limiting drome of hypoglycemia unawareness, or(DKA) or nonketotic hyperosmolar stated factor in the glycemic management of type hypoglycemia-associated autonomic fail-life-threatening conditions that require 1 and insulin-treated type 2 diabetes (199). ure, can severely compromise stringentimmediate medical care to prevent com- Mild hypoglycemia may be inconvenient or diabetes control and quality of life. Theplications and death. Any condition lead- frightening to patients with diabetes, and deficient counter-regulatory hormone re-ing to deterioration in glycemic control more severe hypoglycemia can cause acute lease and autonomic responses in thisnecessitates more frequent monitoring harm to the person with diabetes or others, syndrome are both risk factors for, andof blood glucose and (in ketosis-prone if it causes falls, motor vehicle accidents, or caused by, hypoglycemia. A corollary topatients) urine or blood ketones. Marked other injury. A large cohort study suggested this “vicious cycle” is that several weeks ofhyperglycemia requires temporary ad- that among older adults with type 2 avoidance of hypoglycemia has beenjustment of the treatment program and, diabetes, a history of severe hypoglyce- demonstrated to improve counterregula-if accompanied by ketosis, vomiting, or mia was associated with greater risk of tion and awareness to some extent inalteration in level of consciousness, im- dementia (200). Conversely, evidence many patients (202). Hence, patients withmediate interaction with the diabetes from the DCCT/EDIC study, which in- one or more episodes of severe hypoglyce-care team. The patient treated with non- volved younger type 1 patients, suggested mia may benefit from at least short-term re-insulin therapies or MNT alone may tem- no association of frequency of severe hypo- laxation of glycemic targets.porarily require insulin. Adequate fluid glycemia with cognitive decline (201).and caloric intake must be assured. In- Treatment of hypoglycemia (plasma glucose L. Bariatric surgeryfection or dehydration are more likely to ,70 mg/dL) requires ingestion of glucose- Recommendationsnecessitate hospitalization of the person or carbohydrate-containing foods. The c Bariatric surgery may be considered forwith diabetes than the person without acute glycemic response correlates better adults with BMI .35 kg/m2 and type 2diabetes. with the glucose content than with the car- diabetes, especially if the diabetes or The hospitalized patient should be bohydrate content of the food. Although associated comorbidities are difficult totreated by a physician with expertise in pure glucose is the preferred treatment, control with lifestyle and pharmaco-the management of diabetes. For further any form of carbohydrate that contains glu- logic therapy. (B)information on management of patients cose will raise blood glucose. Added fat may c Patients with type 2 diabetes who havewith hyperglycemia in the hospital, see retard and then prolong the acute glycemic undergone bariatric surgery need life-section IX.A. Diabetes Care in the Hospital. response. Ongoing activity of insulin or in- long lifestyle support and medical moni-For further information on management of sulin secretagogues may lead to recurrence toring. (B)DKA or nonketotic hyperosmolar state, of hypoglycemia unless further food is in- c Although small trials have shown gly-refer to the ADA consensus statement on gested after recovery. cemic benefit of bariatric surgery inhyperglycemic crises (198). Severe hypoglycemia (where the in- patients with type 2 diabetes and BMI dividual requires the assistance of another of 30–35 kg/m2, there is currently in-K. Hypoglycemia person and cannot be treated with oral sufficient evidence to generally rec-Recommendations carbohydrate due to confusion or un- ommend surgery in patients with BMIc Glucose (15–20 g) is the preferred consciousness) should be treated using ,35 kg/m2 outside of a research pro- treatment for the conscious individual emergency glucagon kits, which require a tocol. (E) with hypoglycemia, although any form prescription. Those in close contact with, c The long-term benefits, cost-effectiveness, of carbohydrate that contains glucose or having custodial care of, people with and risks of bariatric surgery in indi- may be used. If SMBG 15 min after hypoglycemia-prone diabetes (family viduals with type 2 diabetes should be treatment shows continued hypoglyce- members, roommates, school personnel, studied in well-designed controlled mia, the treatment should be repeated. child care providers, correctional institu- trials with optimal medical and lifestyle Once SMBG glucose returns to normal, tion staff, or coworkers), should be instruc- therapy as the comparator. (E) the individual should consume a meal or ted in use of such kits. An individual does snack to prevent recurrence of hypo- not need to be a health care professional to Gastric reduction surgery, either gas- glycemia. (E) safely administer glucagon. Care should be tric banding or procedures that involvecare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S27
  • 18. Position Statementbypassing, transposing, or resecting sec- (207). Recent retrospective analyses and specifically in people with diabetes, obser-tions of the small intestine, when part of a modeling studies suggest that these proce- vational studies of patients with a variety ofcomprehensive team approach, can be an dures may be cost-effective, when one con- chronic illnesses, including diabetes, showeffective weight loss treatment for severe siders reduction in subsequent health care that these conditions are associated with anobesity, and national guidelines support costs (208–210). increase in hospitalizations for influenzaits consideration for people with type 2 Some caution about the benefits of and its complications. People with diabetesdiabetes who have BMI .35 kg/m2. Bariat- bariatric surgery might come from recent may be at increased risk of the bacteremicric surgery has been shown to lead to near- studies. A propensity score–adjusted form of pneumococcal infection andor complete normalization of glycemia in analyses of older severely obese patients have been reported to have a high risk;55–95% of patients with type 2 diabetes, with high baseline mortality in Veterans of nosocomial bacteremia, which has adepending on the surgical procedure. A Affairs Medical Centers found that the use mortality rate as high as 50% (213).meta-analysis of studies of bariatric surgery of bariatric surgery was not associated Safe and effective vaccines are avail-involving 3,188 patients with diabetes re- with decreased mortality compared with able that can greatly reduce the risk ofported that 78% had remission of diabe- usual care during a mean 6.7 years of serious complications from these diseasestes (normalization of blood glucose levels follow-up (211). A study that followed pa- (214,215). In a case-control series, influ-in the absence of medications), and that tients who had undergone laparoscopic enza vaccine was shown to reduce diabe-the remission rates were sustained in adjustable gastric banding (LAGB) for 12 tes-related hospital admission by as muchstudies that had follow-up exceeding 2 years found that 60% were satisfied with as 79% during flu epidemics (214). Thereyears (203). Remission rates tend to be the procedure. Nearly one of three pa- is sufficient evidence to support that peo-lower with procedures that only constrict tients experienced band erosion, and al- ple with diabetes have appropriate sero-the stomach and higher with those that most half had required removal of their logic and clinical responses to thesebypass portions of the small intestine. bands. The authors’ conclusion was that, vaccinations. The Centers for DiseaseAdditionally, there is a suggestion that in- “LAGB appears to result in relatively poor Control and Prevention (CDC) Advisorytestinal bypass procedures may have gly- long-term outcomes” (212). Studies of the Committee on Immunization Practicescemic effects that are independent of their mechanisms of glycemic improvement recommends influenza and pneumococcaleffects on weight, perhaps involving the and long-term benefits and risks of bariat- vaccines for all individuals with diabetesincretin axis. ric surgery in individuals with type 2 di- (http://www.cdc.gov/vaccines/recs/). One RCT compared adjustable gastric abetes, especially those who are not At the time these standards went tobanding to “best available” medical and severely obese, will require well-designed press, the CDC was considering recom-lifestyle therapy in subjects with type 2 clinical trials, with optimal medical and mendations to immunize all or some adultsdiabetes diagnosed less than 2 years be- lifestyle therapy of diabetes and cardiovas- with diabetes for hepatitis B. ADA awaitsfore randomization and with BMI 30–40 cular risk factors as the comparator. the final recommendations and will sup-kg/m2 (204). In this trial, 73% of surgi- port them when they are released in 2012.cally treated patients achieved “remis- M. Immunizationsion” of their diabetes, compared with Recommendations VI. PREVENTION AND13% of those treated medically. The latter c Annually provide an influenza vaccine MANAGEMENT OF DIABETESgroup lost only 1.7% of body weight, sug- to all diabetic patients $6 months of COMPLICATIONSgesting that their therapy was not opti- age. (C)mal. Overall the trial had 60 subjects, c Administer pneumococcal polysaccha- A. CVDand only 13 had a BMI ,35 kg/m2, mak- ride vaccine to all diabetic patients $2 CVD is the major cause of morbidity anding it difficult to generalize these results years of age. A one-time revaccination is mortality for individuals with diabeteswidely to diabetic patients who are less recommended for individuals .64 years and the largest contributor to the directseverely obese or with longer duration of age previously immunized when and indirect costs of diabetes. The com-of diabetes. In a more recent study involv- they were ,65 years of age if the vac- mon conditions coexisting with type 2ing 110 patients with type 2 diabetes cine was administered .5 years ago. diabetes (e.g., hypertension and dyslipi-and a mean BMI of 47 kg/m2, Roux-en-Y Other indications for repeat vaccina- demia) are clear risk factors for CVD, andgastric bypass resulted in a mean loss of tion include nephrotic syndrome, diabetes itself confers independent risk.excess weight of 63% at 1 year and 84% at chronic renal disease, and other immu- Numerous studies have shown the effi-2 years (205). nocompromised states, such as after cacy of controlling individual cardiovas- Bariatric surgery is costly in the short transplantation. (C) cular risk factors in preventing or slowingterm and has some risks. Rates of mor- c Administer hepatitis B vaccination to CVD in people with diabetes. Large ben-bidity and mortality directly related to the adults with diabetes as per Centers for efits are seen when multiple risk factorssurgery have been reduced considerably Disease Control and Prevention (CDC) are addressed globally (216,217). There isin recent years, with 30-day mortality rates recommendations. (C) evidence that measures of 10-year coro-now 0.28%, similar to those of laparo- nary heart disease (CHD) risk among U.S.scopic cholecystectomy (206). Longer- Influenza and pneumonia are com- adults with diabetes have improved sig-term concerns include vitamin and mineral mon, preventable infectious diseases asso- nificantly over the past decade (218).deficiencies, osteoporosis, and rare but of- ciated with high mortality and morbidity in 1. Hypertension/blood pressure controlten severe hypoglycemia from insulin hy- the elderly and in people with chronic Recommendationspersecretion. Cohort studies attempting to diseases. Though there are limited studies Screening and diagnosismatch subjects suggest that the procedure reporting the morbidity and mortality of c Blood pressure should be measuredmay reduce longer-term mortality rates influenza and pneumococcal pneumonia at every routine diabetes visit. PatientsS28 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 19. Position Statement found to have systolic blood pressure type of diabetes, age, obesity, and ethnic- stroke, and CVD death; the hazard ratio (SBP) $ 130mmHg or diastolic blood ity. Hypertension is a major risk factor for for the primary end point in the intensive pressure (DBP) $80 mmHg should both CVD and microvascular complica- group was 0.88 (95% CI 0.73–1.06; P 5 have blood pressure confirmed on a tions. In type 1 diabetes, hypertension is 0.20). Of the prespecified secondary end separate day. Repeat SBP $130 mmHg or often the result of underlying nephropathy, points, only stroke and nonfatal stroke DBP $80 mmHg confirms a diagnosis of while in type 2 diabetes it usually coexists were statistically significantly reduced by hypertension. (C) with other cardiometabolic risk factors. intensive blood pressure treatment, with Screening and diagnosis. Measurement hazard ratios of 0.59 (95% CI 0.39–0.89,Goals of blood pressure in the office should be P 5 0.01) and 0.63 (95% CI 0.41–0.96,c A goal SBP ,130 mmHg is appropriate done by a trained individual and follow the P 5 0.03), respectively. If this finding is for most patients with diabetes. (C) guidelines established for nondiabetic real, the number needed to treat to preventc Based on patient characteristics and individuals: measurement in the seated one stroke over the course of 5 years with response to therapy, higher or lower position, with feet on the floor and arm intensive blood pressure management is 89. SBP targets may be appropriate. (B) supported at heart level, after 5 min of rest. In predefined subgroup analyses,c Patients with diabetes should be treated Cuff size should be appropriate for the there was a suggestion of heterogeneity to a DBP ,80 mmHg. (B) upper arm circumference. Elevated values (P 5 0.08) based on whether participantsTreatment should be confirmed on a separate day. were randomized to standard or intensivec Patients with a SBP of 130–139 mmHg Because of the clear synergistic risks of glycemia intervention. In those random- or a DBP of 80–89 mmHg may be given hypertension and diabetes, the diagnostic ized to standard glycemic control, the lifestyle therapy alone for a maximum cutoff for a diagnosis of hypertension is event rate for the primary end point was of 3 months and then, if targets are not lower in people with diabetes (blood 1.89 per year in the intensive blood pres- achieved, be treated with addition of pressure $130/80 mmHg) than those sure arm and 2.47 in the standard blood pharmacological agents. (E) without diabetes (blood pressure $140/ pressure arm, while the respective rates inc Patients with more severe hypertension 90 mmHg) (219). the intensive glycemia arm were 1.85 and (SBP $140 or DBP $90 mmHg) at Home blood pressure self-monitoring 1.73. If this observation is true, it suggests diagnosis or follow-up should receive and 24-h ambulatory blood pressure that intensive management to a SBP target pharmacologic therapy in addition to monitoring may provide additional evi- of ,120 mmHg may be of benefit in those lifestyle therapy. (A) dence of “white coat” and masked hyper- who are not targeting an A1C of ,6% and/c Lifestyle therapy for hypertension con- tension and other discrepancies between or that the benefit of intensive blood pres- sists of weight loss, if overweight; Dietary office and “true” blood pressure, and stud- sure management is diminished by more Approaches to Stop Hypertension ies in nondiabetic populations found that intensive glycemia management targeting (DASH)-style dietary pattern, including home measurements may better correlate an A1C of ,6%. reducing sodium and increasing potas- with CVD risk than office measurements Other recent randomized trial data sium intake; moderation of alcohol in- (220,221). However, the preponderance include those of the ADVANCE trial in take; and increased physical activity. (B) of the clear evidence of benefits of treat- which treatment with an ACE inhibitorc Pharmacologic therapy for patients with ment of hypertension in people with dia- and a thiazide-type diuretic reduced diabetes and hypertension should be betes is based on office measurements. the rate of death but not the composite with a regimen that includes either an Treatment goals. Epidemiologic analy- macrovascular outcome. However, the ACE inhibitor or an ARB. If one class is ses show that blood pressure .115/75 ADVANCE trial had no specified targets not tolerated, the other should be sub- mmHg is associated with increased car- for the randomized comparison, and the stituted. (C) diovascular event rates and mortality in mean SBP in the intensive group (135c Multiple drug therapy (two or more individuals with diabetes (219,222,223). mmHg) was not as low as the mean SBP in agents at maximal doses) is generally Randomized clinical trials have demon- the ACCORD standard-therapy group required to achieve blood pressure strated the benefit (reduction of CHD (228). A post hoc analysis of blood pressure targets. (B) events, stroke, and nephropathy) of control in 6,400 patients with diabetes andc Administer one or more antihyperten- lowering blood pressure to ,140 mmHg CAD enrolled in the International Verapa- sive medications at bedtime. (A) systolic and ,80 mmHg diastolic in indi- mil/Trandolapril Study (INVEST) demon-c If ACE inhibitors, ARBs, or diuretics are viduals with diabetes (219,224–226). The strated that “tight control” (,130 mmHg) used, kidney function and serum po- ACCORD trial examined whether blood was not associated with improved cardio- tassium levels should be monitored. (E) pressure lowering to systolic blood pressure vascular outcomes compared with “usualc In pregnant patients with diabetes and (SBP) ,120 mmHg provides greater car- care” (130–140 mmHg) (229). chronic hypertension, blood pressure diovascular protection than an SBP of It is possible that lowering SBP from target goals of 110–129/65–79 mmHg 130–140 mmHg in patients with type 2 di- the low-130s to ,120 mmHg does not are suggested in the interest of long-term abetes at high risk for CVD (227). The further reduce coronary events or death, maternal health and minimizing im- blood pressure achieved in the intensive and that most of the benefit from lowering paired fetal growth. ACE inhibitors and group was 119/64 mmHg and in the stan- blood pressure is achieved by targeting a ARBs are contraindicated during preg- dard group was 133/70 mmHg; the differ- goal ,140 mmHg. However, this has not nancy. (E) ence achieved was attained with an average been formally assessed. Only the ACCORD of 3.4 medications per participant in the blood pressure trial has formally examined Hypertension is a common comor- intensive group and 2.1 in the standard treatment targets significantly ,130bidity of diabetes, affecting the majority of therapy group. The primary outcome mmHg in diabetes. The absence of signifi-patients, with prevalence depending on was a composite of nonfatal MI, nonfatal cant harms, the trends toward benefit incare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S29
  • 20. Position Statementstroke, and the potential heterogeneity therapy of hypertension. In a nonhyper- to optimal doses of at least 3 antihyperten-with respect to intensive glycemia manage- tension trial of high-risk individuals, sive agents of different classifications, onement suggests that previously recommen- including a large subset with diabetes, of which should be a diuretic, cliniciansded targets are reasonable pending further an ACE inhibitor reduced CVD outcomes should consider an evaluation for sec-analyses and results. SBP targets more or (236). In patients with congestive heart ondary forms of hypertension. Growingless stringent than ,130 mmHg may be failure (CHF), including diabetic sub- evidence suggests that there is an associ-appropriate for individual patients, based groups, ARBs have been shown to reduce ation between increase in sleep-timeon response to therapy, medication toler- major CVD outcomes (237–240), and in blood pressure and incidence of CVDance, and individual characteristics, keeping type 2 patients with significant nephropa- events. A recent RCT of 448 participantsin mind that most analyses have suggested thy, ARBs were superior to calcium channel with type 2 diabetes and hypertensionthat outcomes are worse if the SBP is .140 blockers for reducing heart failure (241). demonstrated reduced cardiovascularmmHg. Though evidence for distinct advantages events and mortality with median follow-Treatment strategies. Although there of RAS inhibitors on CVD outcomes in di- up of 5.4 years if at least one antihyperten-are no well-controlled studies of diet abetes remains conflicting (224,235), the sive medication was given at bedtime (243).and exercise in the treatment of hyperten- high CVD risks associated with diabetes, During pregnancy in diabetic womension in individuals with diabetes, the Di- and the high prevalence of undiagnosed with chronic hypertension, target bloodetary Approaches to Stop Hypertension CVD, may still favor recommendations pressure goals of SBP 110–129 mmHg(DASH) study in nondiabetic individuals for their use as first-line hypertension ther- and DBP 65–79 mmHg are reasonable,has shown antihypertensive effects similar apy in people with diabetes (219). as they contribute to long-term maternalto pharmacologic monotherapy. Lifestyle Recently, the blood pressure arm of health. Lower blood pressure levels maytherapy consists of reducing sodium intake the ADVANCE trial demonstrated that be associated with impaired fetal growth.(to ,1,500 mg per day) and excess body routine administration of a fixed combi- During pregnancy, treatment with ACEweight; increasing consumption of fruits, nation of the ACE inhibitor perindopril inhibitors and ARBs is contraindicated,vegetables (8–10 servings per day), and and the diuretic indapamide significantly since they can cause fetal damage. Antihy-low-fat dairy products (2–3 servings per reduced combined microvascular and pertensive drugs known to be effective andday); avoiding excessive alcohol consump- macrovascular outcomes, as well as CVD safe in pregnancy include methyldopa, la-tion (no more than two servings per day in and total mortality. The improved out- betalol, diltiazem, clonidine, and prazosin.men and no more than one serving per comes could also have been due to lower Chronic diuretic use during pregnancy hasday in women) (230); and increasing ac- achieved blood pressure in the perindopril- been associated with restricted maternaltivity levels (219). These nonpharmaco- indapamide arm (228). In addition the plasma volume, which might reduce utero-logical strategies may also positively affect ACCOMPLISH trial showed a decrease placental perfusion (244).glycemia and lipid control. Their effects on in morbidity and mortality in those re- 2. Dyslipidemia/lipid managementcardiovascular events have not been estab- ceiving benazapril and amlodipine versus Recommendationslished. An initial trial of nonpharmacologic benazapril and hydrochlorothiazide. The Screeningtherapy may be reasonable in diabetic indi- compelling benefits of RAS inhibitors inviduals with mild hypertension (SBP 130– diabetic patients with albuminuria or renal c In most adult patients, measure fasting139 mmHg or DBP 80–89 mmHg). If the insufficiency provide additional rationale lipid profile at least annually. In adultsblood pressure is $140 mmHg systolic for use of these agents (see section VI.B. with low-risk lipid values (LDL choles-and/or $90 mmHg diastolic at the time Nephropathy Screening and Treatment). terol ,100 mg/dL, HDL cholesterol .50of diagnosis, pharmacologic therapy If needed to achieve blood pressure targets, mg/dL, and triglycerides ,150 mg/dL),should be initiated along with nonpharma- amlodipine, HCTZ, or chlorthalidone can lipid assessments may be repeated everycologic therapy (219). be added. If estimated glomerular filtration 2 years. (E) Lowering of blood pressure with reg- rate (GFR) is ,30 ml/min/m2, a loop di- Treatment recommendations and goalsimens based on a variety of antihyperten- uretic, rather than HCTZ or chlorthatli- c Lifestyle modification focusing on thesive drugs, including ACE inhibitors, done should be prescribed. Titration of reduction of saturated fat, trans fat, andARBs, b-blockers, diuretics, and calcium and/or addition of further blood pressure cholesterol intake; increase of n-3 fattychannel blockers, has been shown to be medications should be made in timely fash- acids, viscous fiber and plant stanols/effective in reducing cardiovascular events. ion to overcome clinical inertia in achieving sterols; weight loss (if indicated); andSeveral studies suggested that ACE inhibi- blood pressure targets. increased physical activity should betors may be superior to dihydropyridine Evidence is emerging that health in- recommended to improve the lipidcalcium channel blockers in reducing car- formation technology can be used safely and profile in patients with diabetes. (A)diovascular events (231–233). However, a effectively as a tool to enable attainment of c Statin therapy should be added to life-variety of other studies have shown no spe- blood pressure goals. Using a telemonitor- style therapy, regardless of baselinecific advantage to ACE inhibitors as initial ing intervention to direct titrations of anti- lipid levels, for diabetic patients:treatment of hypertension in the general hypertensive medications between medicalhypertensive population, but rather an office visits has been demonstrated to have a ○ with overt CVD. (A)advantage on cardiovascular outcomes profound impact on SBP control (242). ○ without CVD who are over the age of 40of initial therapy with low-dose thiazide An important caveat is that most years and who have one or more otherdiuretics (219,234,235). patients with hypertension require mul- CVD risk factors. (A) In people with diabetes, inhibitors of tidrug therapy to reach treatment goals, c For patients at lower risk than thosethe renin-angiotensin system (RAS) may especially diabetic patients whose targets are above (e.g., those without overt CVDhave unique advantages for initial or early lower (219). If blood pressure is refractoryS30 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 21. Position Statement and under the age of 40 years), statin However, the evidence base for drugs that not definitive, consideration should be therapy should be considered in addi- target these lipid fractions is significantly given to lipid-lowering goals in type 1 di- tion to lifestyle therapy if LDL choles- less robust than that for statin therapy abetic patients similar to those in type 2 terol remains .100 mg/dL or in those (253). Nicotinic acid has been shown to diabetic patients, particularly if they have with multiple CVD risk factors. (E) reduce CVD outcomes (254), although other cardiovascular risk factors.c In individuals without overt CVD, the the study was done in a nondiabetic co- primary goal is an LDL cholesterol ,100 hort. Gemfibrozil has been shown to de- Alternative LDL cholesterol goals. Vir- mg/dL (2.6 mmol/L). (A) crease rates of CVD events in subjects tually all trials of statins and CVD out-c In individuals with overt CVD, a lower without diabetes (255,256) and in the di- comes tested specific doses of statins LDL cholesterol goal of ,70 mg/dL abetic subgroup of one of the larger trials against placebo, other doses of statin, or (1.8 mmol/L), using a high dose of a (255). However, in a large trial specific to other statins, rather than aiming for specific statin, is an option. (B) diabetic patients, fenofibrate failed to re- LDL cholesterol goals (259). Placebo-c If drug-treated patients do not reach duce overall cardiovascular outcomes controlled trials generally achieved LDL the above targets on maximal tolerated (257). cholesterol reductions of 30–40% from statin therapy, a reduction in LDL baseline. Hence, LDL cholesterol lower- cholesterol of ;30–40% from baseline Dyslipidemia treatment and target ing of this magnitude is an acceptable is an alternative therapeutic goal. (A) lipid levels. For most patients with di- outcome for patients who cannot reachc Triglycerides levels ,150 mg/dL (1.7 abetes, the first priority of dyslipidemia LDL cholesterol goals due to severe base- mmol/L) and HDL cholesterol .40 therapy (unless severe hypertriglyceride- line elevations in LDL cholesterol and/or mg/dL (1.0 mmol/L) in men and .50 mia is the immediate issue) is to lower intolerance of maximal, or any, statin mg/dL (1.3 mmol/L) in women, are de- LDL cholesterol to a target goal of ,100 doses. Additionally for those with baseline sirable. However, LDL cholesterol– mg/dL (2.60 mmol/L) (258). Lifestyle in- LDL cholesterol minimally .100 mg/dL, targeted statin therapy remains the tervention, including MNT, increased prescribing statin therapy to lower LDL preferred strategy. (C) physical activity, weight loss, and smok- cholesterol ;30–40% from baseline isc If targets are not reached on maximally ing cessation, may allow some patients to probably more effective than prescrib- tolerated doses of statins, combination reach lipid goals. Nutrition intervention ing just enough to get LDL cholesterol therapy using statins and other lipid- should be tailored according to each pa- slightly ,100 mg/dL. lowering agents may be considered to tient’s age, type of diabetes, pharmacolog- Recent clinical trials in high-risk pa- achieve lipid targets but has not been ical treatment, lipid levels, and other tients, such as those with acute coronary evaluated in outcome studies for either medical conditions and should focus on syndromes or previous cardiovascular CVD outcomes or safety. (E) the reduction of saturated fat, cholesterol, events (260–262), have demonstratedc Statin therapy is contraindicated in preg- and trans unsaturated fat intake and increa- that more aggressive therapy with high nancy. (B) ses in n-3 fatty acids, viscous fiber (such as doses of statins to achieve an LDL cho- in oats, legumes, citrus), and plant stanols/ lesterol of ,70 mg/dL led to a significantEvidence for benefits of lipid-lowering sterols. Glycemic control can also benefi- reduction in further events. Therefore, atherapy. Patients with type 2 diabetes have cially modify plasma lipid levels, particularly reduction in LDL cholesterol to a goal ofan increased prevalence of lipid abnormal- in patients with very high triglycerides and ,70 mg/dL is an option in very-high-ities, contributing to their high risk of poor glycemic control. risk diabetic patients with overt CVDCVD. For the past decade or more, In those with clinical CVD or who are (263).multiple clinical trials demonstrated sig- over 40 years of age with other CVD risk In individual patients, LDL choles-nificant effects of pharmacologic (primarily factors, pharmacological treatment terol lowering with statins is highly vari-statin) therapy on CVD outcomes in sub- should be added to lifestyle therapy able and this variable response is poorlyjects with CHD and for primary CVD pre- regardless of baseline lipid levels. Statins understood (264). Reduction of CVDvention (245). Subanalyses of diabetic are the drugs of choice for lowering LDL events with statins correlates very closelysubgroups of larger trials (246–250) and tri- cholesterol. with LDL cholesterol lowering (245).als specifically in subjects with diabetes In patients other than those described When maximally tolerated doses of sta-(251,252) showed significant primary and above, statin treatment should be consid- tins fail to significantly lower LDL choles-secondary prevention of CVD events 1/2 ered if there is an inadequate LDL choles- terol (,30% reduction from patientsCHD deaths in diabetic populations. Similar terol response to lifestyle modifications baseline), the primary aim of combinationto findings in nondiabetic subjects, reduc- and improved glucose control, or if the therapy should be to achieve additionaltion in “hard” CVD outcomes (CHD death patient has increased cardiovascular risk LDL cholesterol lowering. Niacin, fenofi-and nonfatal MI) can be more clearly seen (e.g., multiple cardiovascular risk factors brate, ezetimibe, and bile acid sequestrantsin diabetic subjects with high baseline or long duration of diabetes). Very little all offer additional LDL cholesterol lower-CVD risk (known CVD and/or very high clinical trial evidence exists for type 2 ing. The evidence that combination therapyLDL cholesterol levels), but overall the patients under the age of 40 years or for for LDL cholesterol lowering provides a sig-benefits of statin therapy in people with type 1 patients of any age. In the Heart nificant increment in CVD risk reductiondiabetes at moderate or high risk for CVD Protection Study (lower age limit: 40 years), over statin therapy alone is still elusive.are convincing. the subgroup of ;600 patients with type 1 Some experts recommend a greater focus Low levels of HDL cholesterol, often diabetes had a reduction in risk propor- on non–HDL cholesterol and apolipopro-associated with elevated triglyceride levels, tionately similar to that of patients with tein B (apoB) in patients who are likely toare the most prevalent pattern of dyslipi- type 2 diabetes, although not statistically have small LDL particles, such as peopledemia in persons with type 2 diabetes. significant (247). Although the data are with diabetes (265).care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S31
  • 22. Position StatementTreatment of other lipoprotein fractions 3. Antiplatelet agents Table 11dSummary of recommendationsor targets. Severe hypertriglyceridemia Recommendations for glycemic, blood pressure, and lipidmay warrant immediate therapy of this c Consider aspirin therapy (75–162 control for most adults with diabetesabnormality with lifestyle and usually mg/day) as a primary prevention strategy A1C ,7.0%*pharmacologic therapy (fibric acid deriv- in those with type 1 or type 2 diabetes at Blood pressure ,130/80 mmHg†ative, niacin, or fish oil) to reduce the risk increased cardiovascular risk (10-year Lipidsof acute pancreatitis. In the absence of risk .10%). This includes most men .50 LDL cholesterol ,100 mg/dLsevere hypertriglyceridemia, therapy years of age or women .60 years of age (,2.6 mmol/L)‡targeting HDL cholesterol or triglycerides who have at least one additional major *More or less stringent glycemic goals may be ap-has intuitive appeal but lacks the evidence risk factor (family history of CVD, hy- propriate for individual patients. Goals should bebase of statin therapy. If the HDL choles- pertension, smoking, dyslipidemia, or individualized based on duration of diabetes, age/lifeterol is ,40 mg/dL and the LDL cholesterol albuminuria). (C) expectancy, comorbid conditions, known CVD or100–129 mg/dL, gemfibrozil or niacin c Aspirin should not be recommended advanced microvascular complications, hypoglycemia unawareness, individual and patient considerations.might be used, especially if a patient is for CVD prevention for adults with †Based on patient characteristics and response tointolerant to statins. Niacin is the most diabetes at low CVD risk (10-year therapy, higher or lower SBP targets may be appro-effective drug for raising HDL choles- CVD risk ,5%, such as in men ,50 priate. ‡In individuals with overt CVD, a lower LDLterol. It can significantly increase blood years and women ,60 years with no cholesterol goal of ,70 mg/dL (1.8 mmol/L), usingglucose at high doses, but recent studies major additional CVD risk factors), a high dose of a statin, is an option.demonstrate that at modest doses (750– since the potential adverse effects2,000 mg/day), significant improvements from bleeding likely offset the potential little effect on CHD death (RR 0.95, 95% CIin LDL cholesterol, HDL cholesterol, and benefits. (C) 0.78–1.15) or total stroke. There was sometriglyceride levels are accompanied by c In patients in these age-groups with evidence of a difference in aspirin effect byonly modest changes in glucose that are multiple other risk factors (e.g., 10-year gender. Aspirin significantly reduced CHDgenerally amenable to adjustment of dia- risk 5–10%), clinical judgment is re- events in men but not in women. Con-betes therapy (266,267). quired. (E) versely, aspirin had no effect on stroke inCombination therapy. Combination c Use aspirin therapy (75–162 mg/day) men but significantly reduced stroke intherapy, with a statin and a fibrate or as a secondary prevention strategy in women. Notably, differences betweenstatin and niacin, may be efficacious for those with diabetes with a history of sexes in aspirin’s effects have not been ob-treatment for all three lipid fractions, but CVD. (A) served in studies of secondary preventionthis combination is associated with an c For patients with CVD and documented (271). In the six trials examined by theincreased risk for abnormal transaminase aspirin allergy, clopidogrel (75 mg/day) ATT collaborators, the effects of aspirinlevels, myositis, or rhabdomyolysis. The should be used. (B) on major vascular events were similar forrisk of rhabdomyolysis is higher with c Combination therapy with ASA (75–162 patients with or without diabetes (RRhigher doses of statins and with renal mg/day) and clopidogrel (75 mg/day) is 0.88, 95% CI 0.67–1.15, and 0.87, 0.79–insufficiency and seems to be lower when reasonable for up to a year after an acute 0.96), respectively. The confidence intervalstatins are combined with fenofibrate coronary syndrome. (B) was wider for those with diabetes becausethan gemfibrozil (268). In the recent of their smaller number.ACCORD study, the combination of fe- Aspirin has been shown to be effective Based on the currently available evi-nofibrate and simvastatin did not reduce in reducing cardiovascular morbidity and dence, aspirin appears to have a modestthe rate of fatal cardiovascular events, mortality in high-risk patients with pre- effect on ischemic vascular events, withnonfatal MI, or nonfatal stroke, as com- vious MI or stroke (secondary prevention). the absolute decrease in events dependingpared with simvastatin alone, in patients Its net benefit in primary prevention on the underlying CVD risk. The mainwith type 2 diabetes who were at high risk among patients with no previous cardio- adverse effects appear to be an increasedfor CVD. However, prespecified sub- vascular events is more controversial, both risk of gastrointestinal bleeding. The ex-group analyses suggested heterogeneity for patients with and without a history of cess risk may be as high as 1–5 per 1,000in treatment effects according to sex, diabetes (271). Two recent RCTs of aspirin per year in real-world settings. In adultswith a benefit of combination therapy specifically in patients with diabetes failed with CVD risk .1% per year, the numberfor men and possible harm for women, to show a significant reduction in CVD end of CVD events prevented will be similar toand a possible benefit for patients with points, raising further questions about the or greater than the number of episodes ofboth triglyceride level $204 mg/dL and efficacy of aspirin for primary prevention in bleeding induced, although these compli-HDL cholesterol level #34 mg/dL (269). people with diabetes (272,273). cations do not have equal effects on long-The AIM-HIGH trial randomized over The Antithrombotic Trialist (ATT) col- term health (274).3,000 patients (about one-third with di- laborators recently published an individual In 2010, a position statement of theabetes) to statin therapy plus or minus patient-level meta-analysis of the six large ADA, AHA, and the American College ofaddition of extended release niacin. The trials of aspirin for primary prevention in Cardiology Foundation (ACCF) updatedtrial was halted early due to no difference the general population. These trials collec- prior joint recommendations for primaryin the primary CVD outcome and a pos- tively enrolled over 95,000 participants, prevention (275). Low-dose (75–162sible increase in ischemic stroke in those including almost 4,000 with diabetes. mg/day) aspirin use for primary preven-on combination therapy (270). Table 11 Overall, they found that aspirin reduced tion is reasonable for adults with diabetessummarizes common treatment goals the risk of vascular events by 12% (relative and no previous history of vascular diseasefor A1C, blood pressure, and LDL cho- risk [RR] 0.88, 95% CI 0.82–0.94). The who are at increased CVD risk (10-year risklesterol. largest reduction was for nonfatal MI with of CVD events .10%) and who are not atS32 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 23. Position Statementincreased risk for bleeding. This generally provides convincing documentation of the subsequent follow-up has intuitive appeal.includes most men over age 50 years and causal link between cigarette smoking and However, recent studies concluded that us-women over age 60 years who also have health risks. Much of the work document- ing this approach fails to identify whichone or more of the following major risk ing the impact of smoking on health does patients with type 2 diabetes will have si-factors: smoking, hypertension, dyslipide- not separately discuss results on subsets of lent ischemia on screening tests (182,280).mia,) family history of premature CVD, or individuals with diabetes, but suggests that Candidates for cardiac testing includealbuminuria. the identified risks are at least equivalent those with 1) typical or atypical cardiac However, aspirin is no longer recom- to those found in the general population. symptoms and 2) an abnormal restingmended for those at low CVD risk (women Other studies of individuals with diabetes ECG. The screening of asymptomatic pa-under age 60 years and men under age 50 consistently demonstrate that smokers tients remains controversial. Intensive med-years with no major CVD risk factors; 10- have a heightened risk of CVD and pre- ical therapy, which would be indicatedyear CVD risk ,5%), as the low benefit is mature death and increased rate of mi- anyway for diabetic patients at high risk forlikely to be outweighed by the risks of sig- crovascular complications of diabetes. CVD, seems to provide equal outcomes tonificant bleeding. Clinical judgment should Smoking may have a role in the develop- invasive revascularization, which raisesbe used for those at intermediate risk ment of type 2 diabetes. questions of how screening results would(younger patients with one or risk factors, The routine and thorough assessment change management. (281,282). There isor older patients with no risk factors; those of tobacco use is important as a means of also some evidence that silent myocardialwith 10-year CVD risk of 5–10%) until fur- preventing smoking or encouraging cessa- ischemia may reverse over time, adding tother research is available. Use of aspirin in tion. A number of large randomized clinical the controversy concerning aggressivepatients under the age of 21 years is contra- trials have demonstrated the efficacy and screening strategies (283). Finally, a recentindicated due to the associated risk of cost-effectiveness of brief counseling in randomized observational trial demon-Reye’s syndrome. smoking cessation, including the use of strated no clinical benefit to routine screen- Average daily dosages used in most quit lines, in the reduction of tobacco use. ing of asymptomatic patients with type 2clinical trials involving patients with di- For the patient motivated to quit, the addi- diabetes and normal ECGs (284). Despiteabetes ranged from 50 to 650 mg but were tion of pharmacological therapy to counsel- abnormal myocardial perfusion imaging inmostly in the range of 100 to 325 mg/day. ing is more effective than either treatment more than one in five patients, cardiac out-There is little evidence to support any alone. Special considerations should in- comes were essentially equal (and very low)specific dose, but using the lowest possi- clude assessment of the level of nicotine in screened versus unscreened patients. Ac-ble dosage may help reduce side-effects dependence, which is associated with dif- cordingly, the overall effectiveness, especially(276). Although platelets from patients ficulty in quitting and relapse (279). the cost-effectiveness, of such an indiscrim-with diabetes have altered function, it is inate screening strategy is now questioned.unclear what, if any, impact that finding 5. CHD screening and treatment Newer noninvasive CAD screeninghas on the required dose of aspirin for car- Recommendations methods, such as computed tomography Screeningdioprotective effects in the patient with di- (CT) and CT angiography have gained in c In asymptomatic patients, routineabetes. There are many alternate pathways popularity. These tests infer the presence screening for CAD is not recommended,for platelet activation that are independent of coronary atherosclerosis by measuring as it does not improve outcomes as longof thromboxane A2 and thus not sensitive the amount of calcium in coronary arteries as CVD risk factors are treated. (A)to the effects of aspirin (277). Therefore, and, in some circumstances, by directwhile “aspirin resistance” appears higher Treatment visualization of luminal stenoses. Althoughin the diabetic patients when measured c In patients with known CVD, consider asymptomatic diabetic patients found toby a variety of ex vivo and in vitro methods ACE inhibitor therapy (C) and use aspirin have a higher coronary disease burden have(platelet aggrenometry, measurement of and statin therapy (A) (if not contra- more future cardiac events (285–287), thethromboxane B2), these observations alone indicated) to reduce the risk of cardio- role of these tests beyond risk stratificationare insufficient to empirically recommend vascular events. In patients with a prior is not clear. Their routine use leads to radi-higher doses of aspirin be used in the di- MI, b-blockers should be continued for ation exposure and may result in unneces-abetic patient at this time. at least 2 years after the event. (B) sary invasive testing such as coronary Clopidogrel has been demonstrated c Longer-term use of b-blockers in the angiography and revascularization proce-to reduce CVD events in diabetic individ- absence of hypertension is reasonable if dures. The ultimate balance of benefit,uals (278). It is recommended as adjunc- well tolerated, but data are lacking. (E) cost, and risks of such an approach intive therapy in the first year after an acute c Avoid TZD treatment in patients with asymptomatic patients remains controver-coronary syndrome or as alternative ther- symptomatic heart failure. (C) sial, particularly in the modern setting ofapy in aspirin-intolerant patients. c Metformin may be used in patients with aggressive CVD risk factor control. stable CHF if renal function is normal. In all patients with diabetes, cardio-4. Smoking cessation It should be avoided in unstable or hos- vascular risk factors should be assessed atRecommendations pitalized patients with CHF. (C) least annually. These risk factors includec Advise all patients not to smoke. (A) dyslipidemia, hypertension, smoking, ac Include smoking cessation counseling Screening for CAD is reviewed in a positive family history of premature coro- and other forms of treatment as a rou- recently updated consensus statement nary disease, and the presence of micro- or tine component of diabetes care. (B) (177). To identify the presence of CAD in macroalbuminuria. Abnormal risk factors diabetic patients without clear or suggestive should be treated as described elsewhere in A large body of evidence from epide- symptoms, a risk factor–based approach to these guidelines. Patients at increased CHDmiological, case-control, and cohort studies the initial diagnostic evaluation and risk should receive aspirin and a statin, andcare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S33
  • 24. Position StatementACE inhibitor or ARB therapy if hyperten- kidney disease, difficult management of rise in potassium compared with ACEsive, unless there are contraindications to a issues, or advanced kidney disease. (B) inhibitors in people with nephropathyparticular drug class. While clear benefit (306,307). Combinations of drugs thatexists for ACE inhibitor and ARB therapy in Diabetic nephropathy occurs in 20– block the rennin-angiotensin-aldosteronepatients with nephropathy or hyperten- 40% of patients with diabetes and is the system (e.g., an ACE inhibitor plus ansion, the benefits in patients with CVD in single leading cause of end-stage renal ARB, a mineralocorticoid antagonist, or athe absence of these conditions is less clear, disease (ESRD). Persistent albuminuria direct renin inhibitor) have been shown toespecially when LDL cholesterol is con- in the range of 30–299 mg/24 h (micro- provide additional lowering of albuminuriacomitantly controlled (288,289). albuminuria) has been shown to be the (308–311). However, the long-term effects earliest stage of diabetic nephropathy in of such combinations on renal or cardiovas-B. Nephropathy screening and type 1 diabetes and a marker for develop- cular outcomes have not yet been evaluatedtreatment ment of nephropathy in type 2 diabetes. in clinical trials and they are associated withRecommendations Microalbuminuria is also a well-established increased risk for hyperkalemia.General recommendations marker of increased CVD risk (290,291). Other drugs, such as diuretics, cal-c To reduce the risk or slow the pro- Patients with microalbuminuria who cium channel blockers, and b-blockers, gression of nephropathy, optimize glu- progress to macroalbuminuria ($300 should be used as additional therapy to cose control. (A) mg/24 h) are likely to progress to ESRD further lower blood pressure in patientsc To reduce the risk or slow the pro- (292,293). However, a number of interven- already treated with ACE inhibitors or gression of nephropathy, optimize blood tions have been demonstrated to reduce ARBs (241), or as alternate therapy in pressure control. (A) the risk and slow the progression of renal the rare individual unable to tolerateScreening disease. ACE inhibitors or ARBs.c Perform an annual test to assess urine Intensive diabetes management with Studies in patients with varying stages albumin excretion in type 1 diabetic the goal of achieving near-normoglycemia of nephropathy have shown that protein patients with diabetes duration of $5 has been shown in large prospective restriction of dietary protein helps slow years and in all type 2 diabetic patients randomized studies to delay the onset the progression of albuminuria, GFR de- starting at diagnosis. (B) of microalbuminuria and the progression of cline, and occurrence of ESRD (312–c Measure serum creatinine at least annu- micro- to macroalbuminuria in patients with 315). Dietary protein restriction should ally in all adults with diabetes regardless type 1 (294,295) and type 2 (73,74,78,79) be considered particularly in patients of the degree of urine albumin excretion. diabetes. The UKPDS provided strong evi- whose nephropathy seems to be progress- The serum creatinine should be used to dence that control of blood pressure can re- ing despite optimal glucose and blood estimate GFR and stage the level of chronic duce the development of nephropathy pressure control and use of ACE inhibitor kidney disease (CKD), if present. (E) (224). In addition, large prospective ran- and/or ARBs (315).Treatment domized studies in patients with type 1 Assessment of albuminuria statusc In the treatment of the nonpregnant diabetes have demonstrated that achieve- and renal function. Screening for patient with micro- or macroalbuminuria, ment of lower levels of SBP (,140 mmHg) microalbuminuria can be performed by either ACE inhibitors or ARBs should be resulting from treatment using ACE inhib- measurement of the albumin-to-creatinine used. (A) itors provides a selective benefit over other ratio in a random spot collection; 24-h orc If one class is not tolerated, the other antihypertensive drug classes in delaying timed collections are more burdensome should be substituted. (E) the progression from micro- to macroalbu- and add little to prediction or accuracyc Reduction of protein intake to 0.8–1.0 minuria and can slow the decline in GFR in (316,317). Measurement of a spot urine g z kg body wt21 z day21 in individuals patients with macroalbuminuria (296– for albumin only, whether by immuno- with diabetes and the earlier stages of 298). In type 2 diabetes with hypertension assay or by using a dipstick test specific CKD and to 0.8 g z kg body wt21 z day21 and normoalbuminuria, RAS inhibition for microalbumin, without simultaneously in the later stages of CKD may improve has been demonstrated to delay onset measuring urine creatinine, is somewhat measures of renal function (urine albu- of microalbuminuria in two studies less expensive but susceptible to false- min excretion rate, GFR) and is recom- (299,300). In the latter study, there was negative and false-positive determinations mended. (B) an unexpected higher rate of fatal cardio- as a result of variation in urine concentra-c When ACE inhibitors, ARBs, or diuretics vascular events with olmesartan among pa- tion due to hydration and other factors. are used, monitor serum creatinine and tients with preexisting CHD. potassium levels for the development of ACE inhibitors have been shown to increased creatinine and hyperkalemia. reduce major CVD outcomes (i.e., MI, stroke, (E) death) in patients with diabetes (236), thusc Continued monitoring of urine albu- Table 12dDefinitions of abnormalities in further supporting the use of these agents min excretion to assess both response albumin excretion in patients with microalbuminuria, a CVD to therapy and progression of disease is risk factor. ARBs do not prevent microalbu- reasonable. (E) minuria in normotensive patients with type Spot collection (mg/mgc When estimated GFR is ,60 ml z min/ 1 or type 2 diabetes (301,302); however, Category creatinine) 1.73 m2, evaluate and manage potential ARBs have been shown to reduce the rate of complications of CKD. (E) Normal ,30 progression from micro- to macroalbumi-c Consider referral to a physician expe- Microalbuminuria 30–299 nuria as well as ESRD in patients with type rienced in the care of kidney disease Macro (clinical)- 2 diabetes (303–305). Some evidence sug- for uncertainty about the etiology of albuminuria $300 gests that ARBs have a smaller magnitudeS34 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 25. Position StatementTable 13dStages of CKD should not delay educating their patients about the progressive nature of diabetic GFR (ml/min per 1.73 m2 kidney disease; the renal preservation ben-Stage Description body surface area) efits of aggressive treatment of blood pres- sure, blood glucose, and hyperlipidemia;1 Kidney damage* with normal or increased GFR $90 and the potential need for renal replace-2 Kidney damage* with mildly decreased GFR 60–89 ment therapy.3 Moderately decreased GFR 30–594 Severely decreased GFR 15–29 C. Retinopathy screening and5 Kidney failure ,15 or dialysis treatment*Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests. Adapted from ref. 317. Recommendations General recommendations Abnormalities of albumin excretion Complications of kidney disease cor-are defined in Table 12. Because of vari- relate with level of kidney function. When c To reduce the risk or slow the progressionability in urinary albumin excretion the eGFR is ,60 mL/min/1.73 m2, screen- of retinopathy, optimize glycemic con-(UAE), two of three specimens collected ing for complications of CKD is indicated trol. (A)within a 3- to 6-month period should be (Table 14). Early vaccination against hepa- c To reduce the risk or slow the pro-abnormal before considering a patient to titis B is indicated in patients likely to prog- gression of retinopathy, optimize bloodhave crossed one of these diagnostic ress to end-stage kidney disease. pressure control. (A)thresholds. Exercise within 24 h, infec- Consider referral to a physician expe- Screeningtion, fever, CHF, marked hyperglycemia, rienced in the care of kidney disease when c Adults and children aged 10 years orand marked hypertension may elevate there is uncertainty about the etiology of older with type 1 diabetes should haveUAE over baseline values. kidney disease (heavy proteinuria, active an initial dilated and comprehensive Information on presence of abnormal urine sediment, absence of retinopathy, eye examination by an ophthalmologistUAE in addition to level of GFR may be rapid decline in GFR, resistant hyperten- or optometrist within 5 years after theused to stage CKD. The National Kidney sion). Other triggers for referral may include onset of diabetes. (B)Foundation classification (Table 13) is difficult management issues (anemia, sec- c Patients with type 2 diabetes shouldprimarily based on GFR levels and there- ondary hyperparathyroidism, metabolic have an initial dilated and comprehen-fore differs from other systems in which bone disease, or electrolyte disturbance), sive eye examination by an ophthalmol-staging is based primarily on UAE (318). or advanced kidney disease. The threshold ogist or optometrist shortly after theStudies have found decreased GFR in the for referral may vary depending on the diagnosis of diabetes. (B)absence of increased UAE in a substantial frequency with which a provider encoun- c Subsequent examinations for type 1percentage of adults with diabetes (319). ters diabetic patients with significant and type 2 diabetic patients should beSerum creatinine should therefore be mea- kidney disease. Consultation with a ne- repeated annually by an ophthalmolo-sured at least annually in all adults with phrologist when Stage 4 CKD develops has gist or optometrist. Less-frequent examsdiabetes, regardless of the degree of UAE. been found to reduce cost, improve quality (every 2–3 years) may be considered Serum creatinine should be used to of care, and keep people off dialysis longer following one or more normal eye ex-estimate GFR and to stage the level of CKD, (322). However, nonrenal specialists ams. Examinations will be requiredif present. Estimated GFR (eGFR) is com-monly co-reported by laboratories, or can Table 14dManagement of CKD in diabetesbe estimated using formulae such as theModification of Diet in Renal Disease GFR Recommended(MDRD) study equation (320). Recent re-ports have indicated that the MDRD is All patients Yearly measurement of creatinine, UAE, potassiummore accurate for the diagnosis and strati- 45-60 Referral to nephrology if possibility for nondiabetic kidney disease existsfication of CKD in patients with diabetes (duration type 1 diabetes ,10 years, heavy proteinuria, abnormal findingsthan the Cockcroft-Gault equation (321). on renal ultrasound, resistant hypertension, rapid fall in GFR, or activeGFR calculators are available at http:// urinary sediment on ultrasound)www.nkdep.nih.gov. Consider need for dose adjustment of medications The role of continued annual quanti- Monitor eGFR every 6 monthstative assessment of albumin excretion Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus,after diagnosis of microalbuminuria and parathyroid hormone at least yearlyinstitution of ACE inhibitor or ARB ther- Assure vitamin D sufficiencyapy and blood pressure control is unclear. Consider bone density testingContinued surveillance can assess both Referral for dietary counselingresponse to therapy and progression of 30–44 Monitor eGFR every 3 monthsdisease. Some suggest that reducing ab- Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroidnormal albuminuria (.30 mg/g) to the nor- hormone, hemoglobin, albumin, weight every 3–6 monthsmal or near-normal range may improve Consider need for dose adjustment of medicationsrenal and cardiovascular prognosis, but ,30 Referral to nephrologiststhis approach has not been formally evalu- Adapted from National Kidney Foundation guidelines (available at http://www.kidney.org/professionals/ated in prospective trials. KDOQI/guideline_diabetes/).care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S35
  • 26. Position Statement more frequently if retinopathy is pro- has been shown to decrease the progres- the time of diabetes diagnosis, should gressing. (B) sion of retinopathy (224), although tight have an initial dilated and comprehensivec High-quality fundus photographs can targets (systolic ,120 mmHg) do not im- eye examination soon after diagnosis. detect most clinically significant diabetic part additional benefit (80). Several case Examinations should be performed by retinopathy. Interpretation of the images series and a controlled prospective study an ophthalmologist or optometrist who is should be performed by a trained eye suggest that pregnancy in type 1 diabetic pa- knowledgeable and experienced in diag- care provider. While retinal photogra- tients may aggravate retinopathy (326,327); nosing the presence of diabetic retinopathy phy may serve as a screening tool for laser photocoagulation surgery can mini- and is aware of its management. Subse- retinopathy, it is not a substitute for a mize this risk (327). quent examinations for type 1 and type 2 comprehensive eye exam, which should One of the main motivations for diabetic patients are generally repeated be performed at least initially and at in- screening for diabetic retinopathy is the annually. Less-frequent exams (every 2–3 tervals thereafter as recommended by an established efficacy of laser photocoagu- years) may be cost-effective after one or eye care professional. (E) lation surgery in preventing visual loss. more normal eye exams, and in a popula-c Women with preexisting diabetes who Two large trials, the Diabetic Retinopathy tion with well-controlled type 2 diabetes are planning pregnancy or who have Study (DRS) in patients with PDR and the there was essentially no risk of development become pregnant should have a com- Early Treatment Diabetic Retinopathy of significant retinopathy with a 3-year in- prehensive eye examination and be Study (ETDRS) in patients with macular terval after a normal examination (331). counseled on the risk of development edema, provide the strongest support for Examinations will be required more fre- and/or progression of diabetic retinopa- the therapeutic benefits of photocoagu- quently if retinopathy is progressing (332). thy. Eye examination should occur in lation surgery. The DRS (328) showed The use of retinal photography with the first trimester with close follow-up that panretinal photocoagulation surgery remote reading by experts has great po- throughout pregnancy and for 1 year reduced the risk of severe vision loss from tential in areas where qualified eye care postpartum. (B) PDR from 15.9% in untreated eyes to professionals are not available and may 6.4% in treated eyes, with greatest risk- also enhance efficiency and reduce costsTreatment to-benefit ratio in those with baseline dis- when the expertise of ophthalmologistsc Promptly refer patients with any level ease (disc neovascularization or vitreous can be utilized for more complex exami- of macular edema, severe NPDR, or any hemorrhage). nations and for therapy (333). In-person PDR to an ophthalmologist who is The ETDRS (329) established the ben- exams are still necessary when the photos knowledgeable and experienced in the efit of focal laser photocoagulation surgery are unacceptable and for follow-up of de- management and treatment of diabetic in eyes with macular edema, particularly tected abnormalities. Photos are not a retinopathy. (A) those with clinically significant macular substitute for a comprehensive eye exam,c Laser photocoagulation therapy is in- edema, with reduction of doubling of the which should be performed at least initially dicated to reduce the risk of vision loss visual angle (e.g., 20/50 to 20/100) from and at intervals thereafter as recommended in patients with high-risk PDR, clini- 20% in untreated eyes to 8% in treated by an eye care professional. Results of eye cally significant macular edema, and in eyes. The ETDRS also verified the benefits examinations should be documented and cases of severe NPDR. (A) of panretinal photocoagulation for high- transmitted to the referring health care pro-c The presence of retinopathy is not a risk PDR, and in older-onset patients with fessional. contraindication to aspirin therapy for severe NPDR or less-than-high-risk PDR. cardioprotection, as this therapy does Laser photocoagulation surgery in D. Neuropathy screening and not increase the risk of retinal hem- both trials was beneficial in reducing the treatment orrhage. (A) risk of further visual loss, but generally Recommendations not beneficial in reversing already dimin- c All patients should be screened for distal Diabetic retinopathy is a highly spe- ished acuity. Recombinant monoclonal symmetric polyneuropathy (DPN) start-cific vascular complication of both type 1 antibody to vascular endothelial growth ing at diagnosis of type 2 diabetes andand type 2 diabetes, with prevalence strongly factor is an emerging therapy that seems 5 years after the diagnosis of type 1 di-related to the duration of diabetes. Diabetic to halt progression of macular edema and abetes and at least annually thereafter,retinopathy is the most frequent cause of may in fact improve vision in some patients using simple clinical tests. (B)new cases of blindness among adults aged (330). c Electrophysiological testing is rarely20–74 years. Glaucoma, cataracts, and other The preventive effects of therapy and needed, except in situations where thedisorders of the eye occur earlier and more the fact that patients with PDR or macular clinical features are atypical. (E)frequently in people with diabetes. edema may be asymptomatic provide c Screening for signs and symptoms of In addition to duration of diabetes, strong support for a screening program to cardiovascular autonomic neuropathyother factors that increase the risk of, or detect diabetic retinopathy. As retinopa- should be instituted at diagnosis of typeare associated with, retinopathy include thy is estimated to take at least 5 years to 2 diabetes and 5 years after the diagnosischronic hyperglycemia (323), nephropa- develop after the onset of hyperglycemia, of type 1 diabetes. Special testing is rarelythy (324), and hypertension (325). Inten- patients with type 1 diabetes should have needed and may not affect managementsive diabetes management with the goal of an initial dilated and comprehensive eye or outcomes. (E)achieving near normoglycemia has been examination within 5 years after the onset c Medications for the relief of specificshown in large prospective randomized of diabetes. Patients with type 2 diabetes, symptoms related to painful DPN andstudies to prevent and/or delay the onset who generally have had years of undiag- autonomic neuropathy are recommended,and progression of diabetic retinopathy nosed diabetes and who have a significant as they improve the quality of life of the(61,73,74,80). Lowering blood pressure risk of prevalent diabetic retinopathy at patient. (E)S36 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 27. Position Statement The diabetic neuropathies are hetero- gastroparesis, erectile dysfunction, sudomo- Autonomic neuropathygeneous with diverse clinical manifesta- tor dysfunction, impaired neurovascular Gastroparesis symptoms may improvetions. They may be focal or diffuse. Most function, and potentially autonomic fail- with dietary changes and prokinetic agentscommon among the neuropathies are ure in response to hypoglycemia. such as metoclopramide or erythromy-chronic sensorimotor DPN and autonomic Cardiovascular autonomic neuropathy cin. Treatments for erectile dysfunctionneuropathy. Although DPN is a diagnosis (CAN), a CVD risk factor (93), is the most may include phosphodiesterase type 5of exclusion, complex investigations to studied and clinically important form of inhibitors, intracorporeal or intraurethralexclude other conditions are rarely needed. diabetic autonomic neuropathy. CAN may prostaglandins, vacuum devices, or penile The early recognition and appropriate be indicated by resting tachycardia (.100 prostheses. Interventions for other mani-management of neuropathy in the patient bpm) or orthostasis (a fall in SBP .20 festations of autonomic neuropathy arewith diabetes is important for a number of mmHg upon standing without an appro- described in an ADA statement on neu-reasons: 1) nondiabetic neuropathies may priate heart rate response); it is also associ- ropathy (335). As with DPN treatments,be present in patients with diabetes and ated with increased cardiac event rates. these interventions do not change the un-may be treatable; 2) a number of treatment Although some societies have developed derlying pathology and natural history ofoptions exist for symptomatic diabetic neu- guidelines for screening for CAN, the the disease process, but may have a pos-ropathy; 3) up to 50% of DPN may be benefits of sophisticated testing beyond itive impact on the quality of life of theasymptomatic and patients are at risk for risk stratification are not clear (339). patient.insensate injury to their feet; 4) autonomic Gastrointestinal neuropathies (e.g.,neuropathy and particularly cardiovascular esophageal enteropathy, gastroparesis, E. Foot careautonomic neuropathy is associated with constipation, diarrhea, fecal incontinence) Recommendationssubstantial morbidity and even mortality. are common, and any section of the gas- c For all patients with diabetes, performSpecific treatment for the underlying nerve trointestinal tract may be affected. Gastro- an annual comprehensive foot exami-damage is currently not available, other paresis should be suspected in individuals nation to identify risk factors predictivethan improved glycemic control, which with erratic glucose control or with upper of ulcers and amputations. The footmay modestly slow progression (79) but gastrointestinal symptoms without other examination should include inspection,not reverse neuronal loss. Effective symp- identified cause. Evaluation of solid-phase assessment of foot pulses, and testing fortomatic treatments are available for some gastric emptying using double-isotope loss of protective sensation (10-g mono-manifestations of DPN (334) and auto- scintigraphy may be done if symptoms filament plus testing any one of the fol-nomic neuropathy. are suggestive, but test results often corre- lowing: vibration using 128-Hz tuning late poorly with symptoms. Constipation is fork, pinprick sensation, ankle reflexes,Diagnosis of neuropathy the most common lower-gastrointestinal or vibration perception threshold). (B)Distal symmetric polyneuropathy symptom but can alternate with episodes of c Provide general foot self-care educationPatients with diabetes should be screened diarrhea. to all patients with diabetes. (B)annually for DPN using tests such as Diabetic autonomic neuropathy is c A multidisciplinary approach is recom-pinprick sensation, vibration perception also associated with genitourinary tract mended for individuals with foot ulcers(using a 128-Hz tuning fork), 10-g mono- disturbances. In men, diabetic autonomic and high-risk feet, especially those with afilament pressure sensation at the distal neuropathy may cause erectile dysfunc- history of prior ulcer or amputation. (B)plantar aspect of both great toes and meta- tion and/or retrograde ejaculation. Eval- c Refer patients who smoke, have loss oftarsal joints, and assessment of ankle re- uation of bladder dysfunction should be protective sensation and structural ab-flexes. Combinations of more than one test performed for individuals with diabetes normalities, or have history of priorhave .87% sensitivity in detecting DPN. who have recurrent urinary tract infections, lower-extremity complications to footLoss of 10-g monofilament perception and pyelonephritis, incontinence, or a palpable care specialists for ongoing preventivereduced vibration perception predict foot bladder. care and life-long surveillance. (C) c Initial screening for peripheral arterialulcers (335). Importantly, in patients with Symptomatic treatmentsneuropathy, particularly when severe, cau- disease (PAD) should include a his-ses other than diabetes should always be DPN tory for claudication and an assess- The first step in management of patients ment of the pedal pulses. Considerconsidered, such as neurotoxic mediations, with DPN should be to aim for stable and obtaining an ankle-brachial index (ABI),heavy metal poisoning, alcohol abuse, vita- optimal glycemic control. Although con- as many patients with PAD are asymp-min B12 deficiency (especially in those tak- trolled trial evidence is lacking, several tomatic. (C)ing metformin for prolonged periods observational studies suggest that neuro- c Refer patients with significant claudi-(336), renal disease, chronic inflammatory pathic symptoms improve not only with cation or a positive ABI for further vas-demyelinating neuropathy, inherited neu- optimization of control, but also with cular assessment and consider exercise,ropathies, and vasculitis (337). the avoidance of extreme blood glucose medications, and surgical options. (C)Diabetic autonomic neuropathy (338) fluctuations. Patients with painful DPNThe symptoms and signs of autonomic may benefit from pharmacological treat- Amputation and foot ulceration, con-dysfunction should be elicited carefully ment of their symptoms; many agents have sequences of diabetic neuropathy and/orduring the history and physical examina- confirmed or probable efficacy confirmed PAD, are common and major causes oftion. Major clinical manifestations of di- in systematic reviews of RCTs (334), with morbidity and disability in people withabetic autonomic neuropathy include several U.S. Food and Drug Administra- diabetes. Early recognition and manage-resting tachycardia, exercise intolerance, tion (FDA)-approved for the manage- ment of risk factors can prevent or delayorthostatic hypotension, constipation, ment of painful DPN. adverse outcomes.care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S37
  • 28. Position Statement The risk of ulcers or amputations is and one other test. One or more abnormal prominent metatarsal heads, bunions) mayincreased in people who have the follow- tests would suggest LOPS, while at least two need extra-wide or -depth shoes. Peopleing risk factors: normal tests (and no abnormal test) would with extreme bony deformities (e.g., Char- rule out LOPS. The last test listed, vibration cot foot) who cannot be accommodatedc Previous amputation assessment using a biothesiometer or sim- with commercial therapeutic footwear mayc Past foot ulcer history ilar instrument, is widely used in the U.S.; need custom-molded shoes.c Peripheral neuropathy however, identification of the patient with Foot ulcers and wound care may re-c Foot deformity LOPS can easily be carried out without this quire care by a podiatrist, orthopedic orc Peripheral vascular disease or other expensive equipment. vascular surgeon, or rehabilitation specialistc Visual impairment Initial screening for PAD should in- experienced in the management of individ-c Diabetic nephropathy (especially patients clude a history for claudication and an uals with diabetes. on dialysis) assessment of the pedal pulses. A diag-c Poor glycemic control nostic ABI should be performed in any VII. ASSESSMENT OF COMMONc Cigarette smoking patient with symptoms of PAD. Due to COMORBID CONDITIONS the high estimated prevalence of PAD in Many studies have been published patients with diabetes and the fact that Recommendationsproposing a range of tests that might usefully many patients with PAD are asymptom- c For patients with risk factors, signs oridentify patients at risk for foot ulceration, atic, an ADA consensus statement on PAD symptoms, consider assessment andcreating confusion among practitioners as to (341) suggested that a screening ABI be treatment for common diabetes-associatedwhich screening tests should be adopted in performed in patients over 50 years of age conditions (see Table 15). (B)clinical practice. An ADA task force was and be considered in patients under 50therefore assembled in 2008 to concisely years of age who have other PAD risk factors In addition to the commonly appre-summarize recent literature in this area and (e.g., smoking, hypertension, hyperlipid- ciated comorbidities of obesity, hyperten-then recommend what should be included emia, or duration of diabetes .10 years). sion, and dyslipidemia, diabetes is alsoin the comprehensive foot exam for adult Refer patients with significant symptoms associated with other diseases or conditionspatients with diabetes. Their recommenda- or a positive ABI for further vascular as- at rates higher than those of age-matchedtions are summarized below, but clinicians sessment and consider exercise, medica- people without diabetes. A few of the moreshould refer to the task force report (340) for tions, and surgical options (341). common comorbidities are describedfurther details and practical descriptions of Patients with diabetes and high-risk herein, and listed in Table 15.how to perform components of the compre- foot conditions should be educated re-hensive foot examination. garding their risk factors and appropriate Hearing impairment At least annually, all adults with di- management. Patients at risk should un- Hearing impairment, both high frequencyabetes should undergo a comprehensive derstand the implications of the loss of and low/mid frequency, is more commonfoot examination to identify high risk con- protective sensation, the importance of foot in people with diabetes, perhaps due toditions. Clinicians should ask about history monitoring on a daily basis, the proper care neuropathy and/or vascular disease. In anof previous foot ulceration or amputation, of the foot, including nail and skin care, NHANES analysis, hearing impairmentneuropathic or peripheral vascular symp- and the selection of appropriate footwear. was about twice as great in people withtoms, impaired vision, tobacco use, and Patients with loss of protective sensation diabetes than in those without diabetes,foot care practices. A general inspection should be educated on ways to substitute after adjusting for age and other riskof skin integrity and musculoskeletal other sensory modalities (hand palpation, factors for hearing impairment (342).deformities should be done in a well-lit visual inspection) for surveillance of early Controlling for age, race, and other demo-room. Vascular assessment would include foot problems. The patients’ understand- graphic factors, high-frequency loss ininspection and assessment of pedal pulses. ing of these issues and their physical abil- those with diabetes was significantly asso- The neurologic exam recommended ity to conduct proper foot surveillance ciated with history of CHD and with pe-is designed to identify loss of protective and care should be assessed. Patients ripheral neuropathy, while low/midsensation (LOPS) rather than early neu- with visual difficulties, physical con- frequency loss was associated with lowropathy. The clinical examination to identify straints preventing movement, or cogni- HDL cholesterol and with poor reportedLOPS is simple and requires no expensive tive problems that impair their ability to health status (343).equipment. Five simple clinical tests (use assess the condition of the foot and to in-of a 10-g monofilament, vibration testing stitute appropriate responses will needusing a 128-Hz tuning fork, tests of pin- other people, such as family members, Table 15dCommon comorbidities forprick sensation, ankle reflex assessment, to assist in their care. which increased risk is associated withand testing vibration perception threshold People with neuropathy or evidence diabeteswith a biothesiometer), each with evidence of increased plantar pressure (e.g., erythema, Hearing impairmentfrom well-conducted prospective clinical warmth, callus, or measured pressure) may Obstructive sleep apneacohort studies, are considered useful in the be adequately managed with well-fitted Fatty liver diseasediagnosis of LOPS in the diabetic foot. The walking shoes or athletic shoes that cushion Low testosterone in mentask force agrees that any of the five tests the feet and redistribute pressure. Callus Periodontal diseaselisted could be used by clinicians to identify can be debrided with a scalpel by a foot care Certain cancersLOPS, although ideally two of these should specialist or other health professional with Fracturesbe regularly performed during the screening experience and training in foot care. People Cognitive impairmentexamdnormally the 10-g monofilament with bony deformities (e.g., hammertoes,S38 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 29. Position StatementObstructive sleep apnea included in the analysis (354). Several prospective study of a community-dwell-Age-adjusted rates of obstructive sleep high-quality RCTs have not shown a sig- ing people over the age of 60 years, theapnea, a risk factor for CVD, are signifi- nificant effect (355). presence of diabetes at baseline signifi-cantly higher (4- to 10-fold) with obesity, cantly increased the age- and sex-adjustedespecially with central obesity, in men Cancer incidence of all-cause dementia, Alz-and women (344). The prevalence in gen- Diabetes (possibly only type 2 diabetes) is heimer disease, and vascular dementiaeral populations with type 2 diabetes may associated with increased risk of cancers compared with rates in those with normalbe up to 23% (345) and in obese partic- of the liver, pancreas, endometrium, colon/ glucose tolerance (363). In a substudy ofipants enrolled in the Look AHEAD trial rectum, breast, and bladder (356). The as- the ACCORD study, there were no differ-exceeded 80% (346). Treatment of sleep sociation may result from shared risk fac- ences in cognitive outcomes between inten-apnea significantly improves quality of tors between type 2 diabetes and cancer sive and standard glycemic control,life and blood pressure control. The evi- (obesity, age, physical inactivity) but may although there was significantly less of adence for a treatment effect on glycemic also be due to hyperinsulinemia or hyper- decrement in total brain volume by MRIcontrol is mixed (347). glycemia (356a). Patients with diabetes in participants in the intensive arm (364). should be encouraged to undergo recom- The effects of hyperglycemia and insulinFatty liver disease mended age- and sex-appropriate cancer on the brain are areas of intense researchUnexplained elevation of hepatic trans- screenings and to reduce their modifiable interest.aminase concentrations are significantly cancer risk factors (obesity, smoking, phys-associated with higher BMI, waist circum- ical inactivity). VIII. DIABETES CARE INference, triglycerides, and fasting insulin SPECIFIC POPULATIONSand with lower HDL cholesterol. Type 2 Fracturesdiabetes and hypertension are indepen- Age-matched hip fracture risk is signifi- A. Children and adolescentsdently associated with transaminase ele- cantly increased in both type 1 (summary 1. Type 1 diabetesvations in women (348). In a prospective RR 6.3) and type 2 diabetes (summary Three-quarters of all cases of type 1 di-analysis, diabetes was significantly associ- RR 1.7) in both sexes (357). Type 1 di- abetes are diagnosed in individuals ,18ated with incident nonalcoholic chronic abetes is associated with osteoporosis, but years of age. It is appropriate to considerliver disease and with hepatocellular car- in type 2 diabetes an increased risk of hip the unique aspects of care and managementcinoma (349). Interventions that improve fracture is seen despite higher bone mineral of children and adolescents with type 1 di-metabolic abnormalities in patients with density (BMD) (358). One study showed abetes. Children with diabetes differ fromdiabetes (weight loss, glycemic control, that prevalent vertebral fractures were sig- adults in many respects, including changestreatment with specific drugs for hyper- nificantly more common in men and in insulin sensitivity related to sexual ma-glycemia or dyslipidemia) are also benefi- women with type 2 diabetes, but were turity and physical growth, ability to pro-cial for fatty liver disease (350). not associated with BMD (359). In three vide self-care, supervision in child care and large observational studies of older adults, school, and unique neurologic vulnerabil-Low testosterone in men femoral neck BMD T-score and the World ity to hypoglycemia and DKA. Attention toMean levels of testosterone are lower in men Health Organization Fracture Risk Algo- such issues as family dynamics, develop-with diabetes compared with age-matched rithm (FRAX) score were associated mental stages, and physiological differen-men without diabetes, but obesity is a major with hip and nonspine fracture, although ces related to sexual maturity are allconfounder (351). The issue of treatment in fracture risk was higher in diabetic partic- essential in developing and implementingasymptomatic men is controversial. The ipants compared with participants without an optimal diabetes regimen. Although rec-evidence for effects of testosterone re- diabetes for a given T-score and age or for a ommendations for children and adoles-placement on outcomes is mixed, and re- given FRAX score risk (360). It is appropri- cents are less likely to be based on clinicalcent guidelines suggest that screening ate to assess fracture history and risk factors trial evidence, expert opinion and a reviewand treatment of men without symptoms in older patients with diabetes and to rec- of available and relevant experimental datais not recommended (352). ommend BMD testing if appropriate for the are summarized in the ADA statement on patient’s age and sex. For at-risk patients, care of children and adolescents with type 1Periodontal disease it is reasonable to consider standard pri- diabetes (365).Periodontal disease is more severe, but mary or secondary prevention strategies Ideally, the care of a child or adoles-not necessarily more prevalent, in pa- (reduce risk factors for falls, ensure ade- cent with type 1 diabetes should be providedtients with diabetes than those without quate calcium and vitamin D intake, and by a multidisciplinary team of specialists(353). Numerous studies have suggested avoid use of medications that lower BMD, trained in the care of children with pediat-associations with poor glycemic control, such as glucocorticoids) and to consider ric diabetes. At the very least, education ofnephropathy, and CVD, but most studies pharmacotherapy for high-risk patients. the child and family should be provided byare highly confounded. A comprehensive For patients with type 2 diabetes with health care providers trained and experi-assessment, and treatment of identified fracture risk factors, avoidance of TZDs enced in childhood diabetes and sensitivedisease, is indicated in patients with dia- is warranted. to the challenges posed by diabetes in thisbetes, but the evidence that periodontal age-group. At the time of initial diagnosis, itdisease treatment improves glycemic Cognitive impairment is essential that diabetes education be pro-control is mixed. A meta-analysis re- Diabetes is associated with significantly in- vided in a timely fashion, with the expec-ported a significant 0.47% improvement creased risk of cognitive decline, a greater tation that the balance between adultin A1C, but noted multiple problems rate of cognitive decline, and increased risk supervision and self-care should be definedwith the quality of the published studies of dementia (361,362). In a 15-year by, and will evolve according to, physical,care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S39
  • 30. Position Statementpsychological, and emotional maturity. glucose targets (369,370) in those fami- dietary intervention and exercise, aimedMNT and psychological support should lies in which both parents and the child at weight control and increased physicalbe provided at diagnosis, and regularly with diabetes participate jointly to per- activity, if appropriate. If target bloodthereafter, by individuals experienced with form the required diabetes-related tasks. pressure is not reached with 3–6 monthsthe nutritional and behavioral needs of the Furthermore, recent studies documenting of lifestyle intervention, pharmacologicgrowing child and family. neurocognitive sequelae of hyperglycemia treatment should be considered. (E)a. Glycemic control in children provide another compelling c Pharmacologic treatment of hyperten-Recommendations motivation for achieving glycemic targets sion (systolic or diastolic blood pressurec Consider age when setting glycemic (371,372). consistently above the 95th percentile goals in children and adolescents with In selecting glycemic goals, the benefits for age, sex, and height or consistently type 1 diabetes. (E) on long-term health outcomes of achieving a .130/80 mmHg, if 95% exceeds that lower A1C should be balanced against the value) should be considered as soon as While current standards for diabetes risks of hypoglycemia and the developmen- the diagnosis is confirmed. (E)management reflect the need to maintain tal burdens of intensive regimens in children c ACE inhibitors should be consideredglucose control as near to normal as safely and youth. Age-specific glycemic and A1C for the initial treatment of hypertension,possible, special consideration should be goals are presented in Table 16. following appropriate reproductivegiven to the unique risks of hypoglycemia b. Screening and management of counseling due to its potential terato-in young children. Glycemic goals may chronic complications in children and genic effects. (E) adolescents with type 1 diabetes c The goal of treatment is a blood pres-need to be modified to take into accountthe fact that most children ,6 or 7 years of i. Nephropathy sure consistently ,130/80 mmHg or Recommendations below the 90th percentile for age, sex,age have a form of “hypoglycemic unaware- c Annual screening for microalbuminuria,ness,” including immaturity of and a rela- and height, whichever is lower. (E) with a random spot urine sample for al-tive inability to recognize and respond to bumin-to-creatinine ratio (ACR), should It is important that blood pressurehypoglycemic symptoms, placing them at be considered once the child is 10 years of measurements are determined correctly,greater risk for severe hypoglycemia and age and has had diabetes for 5 years. (B) using the appropriate size cuff, and withits sequelae. In addition, and unlike the c Treatment with an ACE inhibitor, ti- the child seated and relaxed. Hypertensioncase in adults, young children below the trated to normalization of albumin ex- should be confirmed on at least 3 separateage of 5 years may be at risk for permanent cretion, should be considered when days. Normal blood pressure levels for age,cognitive impairment after episodes of severe elevated ACR is subsequently confirmed sex, and height and appropriate methodshypoglycemia (366–368). Furthermore, on two additional specimens from dif- for determinations are available online atfindings from the DCCT demonstrated that ferent days. (E)near-normalization of blood glucose levels www.nhlbi.nih.gov/health/prof/heart/hbp/was more difficult to achieve in adolescents ii. Hypertension hbp_ped.pdf.than adults. Nevertheless, the increased fre- Recommendations iii. Dyslipidemiaquency of use of basal-bolus regimens and c Initial treatment of high-normal blood Recommendationsinsulin pumps in youth from infancy pressure (systolic or diastolic blood pres- Screeningthrough adolescence has been associated sure consistently above the 90th per- c If there is a family history of hypercho-with more children reaching ADA blood centile for age, sex, and height) includes lesterolemia or a cardiovascular eventTable 16dPlasma blood glucose and A1C goals for type 1 diabetes by age-group Plasma blood glucose goal range (mg/dL)Values by age (years) Before meals Bedtime/overnight A1C RationaleToddlers and 100–180 110–200 ,8.5% c Vulnerability to hypoglycemia preschoolers (0–6) c Insulin sensitivity c Unpredictability in dietary intake and physical activity c A lower goal (,8.0%) is reasonable if it can be achieved without excessive hypoglycemiaSchool age (6–12) 90–180 100–180 ,8% c Vulnerability of hypoglycemia c A lower goal (,7.5%) is reasonable if it can be achieved without excessive hypoglycemiaAdolescents and young 90–130 90–150 ,7.5% c A lower goal (,7.0%) is reasonable if it can be achieved adults (13–19) without excessive hypoglycemiaKey concepts in setting glycemic goals:c Goals should be individualized and lower goals may be reasonable based on benefit-risk assessment.c Blood glucose goals should be modified in children with frequent hypoglycemia or hypoglycemia unawareness.c Postprandial blood glucose values should be measured when there is a discrepancy between preprandial blood glucose values and A1C levels and to help assess glycemia in those on basal/bolus regimens.S40 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 31. Position Statement before age 55 years, or if family history is with type 1 diabetes prior to this age. For diarrhea, weight loss or poor weight gain, unknown, then consider obtaining a postpubertal girls, issues of pregnancy pre- growth failure, abdominal pain, chronic fa- fasting lipid profile on children .2 years vention are paramount, since statins are cat- tigue, malnutrition due to malabsorption, of age soon after diagnosis (after glucose egory X in pregnancy. For more information, and other gastrointestinal problems, and control has been established). If family see section VIII.B. Preconception care. unexplained hypoglycemia or erratic blood history is not of concern, then consider glucose concentrations. iv. Retinopathy the first lipid screening at puberty ($10 Screening for celiac disease includes Recommendations years of age). For children diagnosed measuring serum levels of tissue transglu- c The first ophthalmologic examination with diabetes at or after puberty, con- should be obtained once the child is taminase or anti-endomysial antibodies, sider obtaining a fasting lipid profile then small bowel biopsy in antibody- $10 years of age and has had diabetes soon after diagnosis (after glucose con- positive children. One small study that for 3–5 years. (B) trol has been established). (E) c After the initial examination, annual included children with and without typec For both age-groups, if lipids are ab- 1 diabetes suggested that antibody-positive routine follow-up is generally recom- normal, annual monitoring is reason- but biopsy-negative children were similar mended. Less-frequent examinations able. If LDL cholesterol values are within clinically to those who were biopsy posi- may be acceptable on the advice of an the accepted risk levels (,100 mg/dL tive, and that biopsy-negative children had eye care professional. (E) [2.6 mmol/L]), a lipid profile repeated benefits from a gluten-free diet but worsen- every 5 years is reasonable. (E) ing on a usual diet (387). Because this study Although retinopathy (like albuminuria)Treatment was small, and because children with type 1 most commonly occurs after the onset ofc Initial therapy may consist of optimi- diabetes already need to follow a careful puberty and after 5–10 years of diabetes du- zation of glucose control and MNT diet, it is difficult to advocate for not con- ration (384), it has been reported in prepu- using a Step 2 American Heart Associ- bertal children and with diabetes duration firming the diagnosis by biopsy before ation diet aimed at a decrease in the recommending a gluten-free diet, especially of only 1–2 years. Referrals should be made amount of saturated fat in the diet. (E) in asymptomatic children. In symptomatic to eye care professionals with expertise inc After the age of 10, the addition of a statin children with type 1 diabetes and celiac dis- diabetic retinopathy, an understanding of in patients who, after MNT and lifestyle ease, gluten-free diets reduce symptoms the risk for retinopathy in the pediatric changes, have LDL cholesterol .160 and rates of hypoglycemia (388). population, and experience in counseling mg/dL (4.1 mmol/L), or LDL cholesterol vi. Hypothyroidism the pediatric patient and family on the im- .130 mg/dL (3.4 mmol/L) and one or Recommendations portance of early prevention/intervention. more CVD risk factors, is reasonable. (E) c Consider screening children with typec The goal of therapy is an LDL cholesterol v. Celiac disease 1 diabetes for thyroid peroxidase and value ,100 mg/dL (2.6 mmol/L). (E) Recommendations thyroglobulin antibodies soon after c Consider screening children with type 1 diagnosis. (E) People diagnosed with type 1 diabetes diabetes for celiac disease by measuring c Measuring TSH concentrations soon afterin childhood have a high risk of early tissue transglutaminase or anti-endomysial diagnosis of type 1 diabetes, after metabolicsubclinical (373–375) and clinical (376) antibodies, with documentation of nor- control has been established, is reasonable.CVD. Although intervention data are lack- mal total serum IgA levels, soon after the If normal, consider rechecking every 1–2ing, the American Heart Association (AHA) diagnosis of diabetes. (E) years, especially if the patient developscategorizes children with type 1 diabetes in c Testing should be considered in chil- symptoms of thyroid dysfunction, thyro-the highest tier for cardiovascular risk and dren with growth failure, failure to gain megaly, or an abnormal growth rate. (E)recommends both lifestyle and pharmaco- weight, weight loss, diarrhea, flatulence,logic treatment for those with elevated LDL abdominal pain, or signs of malabsorp- Autoimmune thyroid disease is thecholesterol levels (377,378). Initial therapy tion, or in children with frequent un- most common autoimmune disorder as-should be with a Step 2 AHA diet, which explained hypoglycemia or deterioration sociated with diabetes, occurring in 17–restricts saturated fat to 7% of total calories in glycemic control. (E) 30% of patients with type 1 diabetesand restricts dietary cholesterol to 200 mg c Consider referral to a gastroenterolo- (389). About one-quarter of type 1 chil-per day. Data from randomized clinical tri- gist for evaluation with endoscopy and dren have thyroid autoantibodies at theals in children as young as 7 months of age biopsy for confirmation of celiac disease time of diagnosis of their diabetes (390),indicate that this diet is safe and does not in asymptomatic children with positive and the presence of thyroid autoantibodies isinterfere with normal growth and devel- antibodies. (E) predictive of thyroid dysfunction, generallyopment (379,380). c Children with biopsy-confirmed celiac hypothyroidism but less commonly hyper- Neither long-term safety nor cardio- disease should be placed on a gluten- thyroidism (391). Subclinical hypothyroid-vascular outcome efficacy of statin therapy free diet and have consultation with a ism may be associated with increased risk ofhas been established for children. How- dietitian experienced in managing both symptomatic hypoglycemia (392) and withever, recent studies have shown short-term diabetes and celiac disease. (B) reduced linear growth (393). Hyperthyroid-safety equivalent to that seen in adults, and ism alters glucose metabolism, potentially re-efficacy in lowering LDL cholesterol levels, Celiac disease is an immune-mediated sulting in deterioration of metabolic control.improving endothelial function, and caus- disorder that occurs with increased fre-ing regression of carotid intimal thickening quency in patients with type 1 diabetes c. Self-management(381–383). No statin is approved for use un- (1–16% of individuals compared with 0.3– No matter how sound the medical regi-der the age of 10 years, and statin treatment 1% in the general population) (385,386). men, it can only be as good as the ability ofshould generally not be used in children Symptoms of celiac disease include the family and/or individual to implementcare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S41
  • 32. Position Statementit. Family involvement in diabetes remains ongoing attention be given to comprehen- correctly diagnose one of the monogenican important component of optimal di- sive and coordinated planning for seamless forms of diabetes, as these children mayabetes management throughout childhood transition of all youth from pediatric to be incorrectly diagnosed with type 1 orand into adolescence. Health care providers adult health care (336,337). A comprehen- type 2 diabetes, leading to nonoptimalwho care for children and adolescents, sive discussion regarding the challenges treatment regimens and delays in diagnos-therefore, must be capable of evaluating faced during this period, including specific ing other family members.the behavioral, emotional, and psychosocial recommendations is found in the ADA po- The diagnosis of monogenic diabetesfactors that interfere with implementation sition statement “Diabetes Care for Emerg- should be considered in the followingand then must work with the individual ing Adults: Recommendations for the settings: diabetes diagnosed within theand family to resolve problems that occur Transition from Pediatric to Adult Diabetes first 6 months of life; in children with strongand/or to modify goals as appropriate. Care Systems” (397). family history of diabetes but without typical The National Diabetes Education Pro- features of type 2 diabetes (nonobese, low-d. School and day care gram (NDEP) has materials available to risk ethnic group); in children with mildSince a sizable portion of a child’s day is facilitate the transition process (http:// fasting hyperglycemia (100–150 mg/dLspent in school, close communication ndep.nih.gov/transitions/). [5.5–8.5 mmol]), especially if young andwith and cooperation of school or day nonobese; and in children with diabetescare personnel is essential for optimal di- 2. Type 2 diabetes The incidence of type 2 diabetes in ado- but with negative autoantibodies withoutabetes management, safety, and maximal signs of obesity or insulin resistance. A re-academic opportunities. See the ADA posi- lescents is increasing, especially in ethnic minority populations (28). Distinction cent international consensus document dis-tion statement on diabetes care in the cusses further in detail the diagnosis andschool and day care setting (394) for fur- between type 1 and type 2 diabetes in chil- dren can be difficult, since the prevalence management of children with monogenicther discussion. forms of diabetes (401). of overweight in children continues to risee. Transition from pediatric to adult and since autoantigens and ketosis may becare present in a substantial number of patients B. Preconception careRecommendations with features of type 2 diabetes (including Recommendationsc As teens transition into emerging adult- c A1C levels should be as close to normal obesity and acanthosis nigricans). Such a hood, health care providers and families distinction at the time of diagnosis is critical as possible (,7%) in an individual pa- must recognize their many vulnerabilities since treatment regimens, educational ap- tient before conception is attempted. (B) (B) and prepare the developing teen, be- proaches, and dietary counsel will differ c Starting at puberty, preconception coun- ginning in early to mid adolescence and at markedly between the two diagnoses. seling should be incorporated in the rou- least 1 year prior to the transition. (E) Type 2 diabetes has a significant in- tine diabetes clinic visit for all women ofc Both pediatricians and adult health care childbearing potential. (C) cidence of comorbidities already pres- providers should assist in providing ent at the time of diagnosis (400). It is c Women with diabetes who are contem- support and links to resources for the recommended that blood pressure mea- plating pregnancy should be evaluated teen and emerging adult. (B) surement, a fasting lipid profile, microalbu- and, if indicated, treated for diabetic minuria assessment, and dilated eye retinopathy, nephropathy, neuropathy, Care and close supervision of diabetes examination be performed at the time of and CVD. (B)management is increasingly shifted from diagnosis. Thereafter, screening guide- c Medications used by such women shouldparents and other older adults through- lines and treatment recommendations be evaluated prior to conception, sinceout childhood and adolescence; however, for hypertension, dyslipidemia, microal- drugs commonly used to treat diabetesthe shift from pediatric to adult health care buminuria and retinopathy in youth with and its complications may be contra-providers often occurs very abruptly as the type 2 diabetes are similar to those for indicated or not recommended in preg-older teen enters the next developmental youth with type 1. Additional problems nancy, including statins, ACE inhibitors,stage, referred to as emerging adulthood that may need to be addressed include ARBs, and most noninsulin therapies. (E)(395, 397), a critical period for young peo- polycystic ovarian disease and the vari- c Since many pregnancies are unplanned,ple who have diabetes. During this period ous comorbidities associated with pedi- consider the potential risks and benefitsof major life transitions, youth begin to atric obesity such as sleep apnea, hepatic of medications that are contraindicatedmove out of their parents’ home and must steatosis, orthopedic complications, and in pregnancy in all women of child-become more fully responsible for their di- psychosocial concerns. An ADA consensus bearing potential, and counsel womenabetes care including the many aspects of statement on this subject (30) provides using such medications accordingly. (E)self management, making medical appoint- guidance on the prevention, screening,ments, and financing health care once they and treatment of type 2 diabetes and its Major congenital malformations re-are no longer covered under their parents comorbidities in young people. main the leading cause of mortality andhealth insurance (396,397). In addition to serious morbidity in infants of motherslapses in health care, this is also a period of 3. Monogenic diabetes syndromes with type 1 and type 2 diabetes. Observa-deterioration in glycemic control, increased Monogenic forms of diabetes (neonatal tional studies indicate that the risk of mal-occurrence of acute complications, psy- diabetes or maturity-onset diabetes of formations increases continuously withchosocial and emotional behavioral issues, youth) represent a small fraction of chil- increasing maternal glycemia during theand emergence of chronic complications dren with diabetes (,5%), but the ready first 6–8 weeks of gestation, as defined(396–399). availability of commercial genetic testing is by first-trimester A1C concentrations. There Though scientific evidence continues now enabling a true genetic diagnosis with is no threshold for A1C values belowto be limited, it is clear that early and increasing frequency. It is important to which risk disappears entirely. However,S42 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 33. Position Statementmalformation rates above the 1–2% back- 2) achieve the lowest A1C test results pos- therapy may benefit those with life ex-ground rate of nondiabetic pregnancies sible without excessive hypoglycemia, pectancy at least equal to the time frameappear to be limited to pregnancies in 3) assure effective contraception until stable of primary or secondary preventionwhich first-trimester A1C concentrations and acceptable glycemia is achieved, and 4) trials. (E)are .1% above the normal range for a identify, evaluate, and treat long-term dia- c Screening for diabetes complicationsnondiabetic pregnant woman. betes complications such as retinopathy, should be individualized in older adults, Preconception care of diabetes appears nephropathy, neuropathy, hypertension, but particular attention should be paidto reduce the risk of congenital malforma- and CHD (94). to complications that would lead totions. Five nonrandomized studies com- Among the drugs commonly used in functional impairment. (E)pared rates of major malformations in the treatment of patients with diabetes, ainfants between women who participated number may be relatively or absolutely Diabetes is an important health con-in preconception diabetes care programs contraindicated during pregnancy. Sta- dition for the aging population; at leastand women who initiated intensive di- tins are category X (contraindicated for 20% of patients over the age of 65 yearsabetes management after they were already use in pregnancy) and should be discon- have diabetes, and this number can bepregnant. The preconception care programs tinued before conception, as should ACE expected to grow rapidly in the comingwere multidisciplinary and designed to inhibitors (402). ARBs are category C decades. Older individuals with diabetestrain patients in diabetes self-management (risk cannot be ruled out) in the first tri- have higher rates of premature death, func-with diet, intensified insulin therapy, and mester, but category D (positive evidence tional disability, and coexisting illnessesSMBG. Goals were set to achieve normal of risk) in later pregnancy, and should such as hypertension, CHD, and strokeblood glucose concentrations, and .80% generally be discontinued before preg- than those without diabetes. Older adultsof subjects achieved normal A1C concen- nancy. Since many pregnancies are un- with diabetes are also at greater risk thantrations before they became pregnant. In planned, health care professionals caring other older adults for several commonall five studies, the incidence of major for any woman of childbearing potential geriatric syndromes, such as polyphar-congenital malformations in women who should consider the potential risks and macy, depression, cognitive impairment,participated in preconception care (range benefits of medications that are contrain- urinary incontinence, injurious falls, and1.0–1.7% of infants) was much lower dicated in pregnancy. Women using med- persistent pain.than the incidence in women who did not ications such as statins or ACE inhibitors The American Geriatric Society’sparticipate (range 1.4–10.9% of infants) need ongoing family planning counsel- guidelines for improving the care of the(94). One limitation of these studies is ing. Among the oral antidiabetic agents, older person with diabetes (404) havethat participation in preconception care metformin and acarbose are classified as influenced the following discussion andwas self-selected rather than randomized. category B (no evidence of risk in hu- recommendations. The care of older adultsThus, it is impossible to be certain that mans) and all others as category C. Poten- with diabetes is complicated by their clini-the lower malformation rates resulted tial risks and benefits of oral antidiabetic cal and functional heterogeneity. Somefully from improved diabetes care. None- agents in the preconception period must older individuals developed diabetes yearstheless, the evidence supports the concept be carefully weighed, recognizing that earlier and may have significant complica-that malformations can be reduced or pre- data are insufficient to establish the safety tions; others who are newly diagnosed mayvented by careful management of diabetes of these agents in pregnancy. have had years of undiagnosed diabetesbefore pregnancy. For further discussion of preconcep- with resultant complications or may have Planned pregnancies greatly facilitate tion care, see the ADA consensus statement few complications from the disease. Somepreconception diabetes care. Unfortu- on preexisting diabetes and pregnancy (94) older adults with diabetes are frail and havenately, nearly two-thirds of pregnancies and also the position statement (403) on other underlying chronic conditions, sub-in women with diabetes are unplanned, this subject. stantial diabetes-related comorbidity, orleading to a persistent excess of malfor- limited physical or cognitive functioning.mations in infants of diabetic mothers. To C. Older adults Other older individuals with diabetesminimize the occurrence of these devas- Recommendations have little comorbidity and are active. Lifetating malformations, standard care for all c Older adults who are functional, cog- expectancies are highly variable for thiswomen with diabetes who have child- nitively intact, and have significant life population, but often longer than cliniciansbearing potential, beginning at the onset expectancy should receive diabetes care realize. Providers caring for older adultsof puberty or at diagnosis, should include using goals developed for younger with diabetes must take this heterogeneity1) education about the risk of malforma- adults. (E) into consideration when setting and prior-tions associated with unplanned pregnan- c Glycemic goals for older adults not itizing treatment goals.cies and poor metabolic control; and 2) use meeting the above criteria may be re- There are few long-term studies inof effective contraception at all times, un- laxed using individual criteria, but hy- older adults demonstrating the benefits ofless the patient has good metabolic control perglycemia leading to symptoms or risk intensive glycemic, blood pressure, andand is actively trying to conceive. of acute hyperglycemic complications lipid control. Patients who can be expected Women contemplating pregnancy should be avoided in all patients. (E) to live long enough to reap the benefits ofneed to be seen frequently by a multidis- c Other cardiovascular risk factors should long-term intensive diabetes managementciplinary team experienced in the man- be treated in older adults with con- and who are active, have good cognitiveagement of diabetes before and during sideration of the time frame of benefit function, and are willing should be pro-pregnancy. The goals of preconception and the individual patient. Treatment vided with the needed education and skillscare are to 1) involve and empower the pa- of hypertension is indicated in virtually to do so and be treated using the goals fortient in the management of her diabetes, all older adults, and lipid and aspirin younger adults with diabetes.care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S43
  • 34. Position Statement For patients with advanced diabetes patients with cystic fibrosis who do not mmol/L) is recommended for the ma-complications, life-limiting comorbid ill- have CFRD (B). Use of A1C as a screening jority of critically ill patients. (A)ness, or substantial cognitive or functional test for CFRD is not recommended. (B) ○ More stringent goals, such as 110–140impairment, it is reasonable to set less in- c During a period of stable health the mg/dL (6.1–7.8 mmol/L) may be appro-tensive glycemic target goals. These patients diagnosis of CFRD can be made in cystic priate for selected patients, as long as thisare less likely to benefit from reducing the fibrosis patients according to usual di- can be achieved without significant hy-risk of microvascular complications and agnostic criteria. (E) poglycemia. (C)more likely to suffer serious adverse effects c Patients with CFRD should be treated ○ Critically ill patients require an in-from hypoglycemia. However, patients with insulin to attain individualized travenous insulin protocol that haswith poorly controlled diabetes may be glycemic goals. (A) demonstrated efficacy and safety insubject to acute complications of diabe- c Annual monitoring for complications achieving the desired glucose rangetes, including dehydration, poor wound of diabetes is recommended, beginning without increasing risk for severe hy-healing, and hyperglycemic hyperosmo- 5 years after the diagnosis of CFRD. (E) poglycemia. (E)lar coma. Glycemic goals at a minimum ○ Non–critically ill patients: There is noshould avoid these consequences. CFRD is the most common comorbid- clear evidence for specific blood glucose Although control of hyperglycemia ity in persons with cystic fibrosis, occurring goals. If treated with insulin, premealmay be important in older individuals in about 20% of adolescents and 40–50% blood glucose targets generally ,140with diabetes, greater reductions in mor- of adults. The additional diagnosis of dia- mg/dL (7.8 mmol/L) with randombidity and mortality may result from con- betes in this population is associated with blood glucose ,180 mg/dL (10.0trol of other cardiovascular risk factors worse nutritional status, more severe in- mmol/L) are reasonable, provided theserather than from tight glycemic control flammatory lung disease, and greater mor- targets can be safely achieved. Morealone. There is strong evidence from tality from respiratory failure. Insulin stringent targets may be appropriate inclinical trials of the value of treating hyper- insufficiency related to partial fibrotic de- stable patients with previous tight glyce-tension in the elderly (405,406). There is struction of the islet mass is the primary mic control. Less stringent targets may beless evidence for lipid-lowering and aspirin defect in CFRD. Genetically determined appropriate in those with severe co-therapy, although the benefits of these in- function of the remaining b-cells and insu- morbidities. (E)terventions for primary and secondary pre- lin resistance associated with infection andvention are likely to apply to older adults inflammation may also play a role. Encour- c Scheduled subcutaneous insulin withwhose life expectancies equal or exceed the aging new data suggest that early detection basal, nutritional, and correction com-time frames seen in clinical trials. and aggressive insulin therapy have nar- ponents is the preferred method for Special care is required in prescribing rowed the gap in mortality between cystic achieving and maintaining glucose con-and monitoring pharmacologic therapy in fibrosis patients with and without diabetes, trol in noncritically ill patients.older adults. Metformin is often contra- and have eliminated the difference in mor- c Glucose monitoring should be initiatedindicated because of renal insufficiency or tality between the sexes (407). in any patient not known to be diabeticsignificant heart failure. TZDs can cause Recommendations for the clinical who receives therapy associated withfluid retention, which may exacerbate or management of CFRD can be found in a high-risk for hyperglycemia, includinglead to heart failure. They are contraindi- recent ADA position statement on this high-dose glucocorticoid therapy, ini-cated in patients with CHF (New York topic (408). tiation of enteral or parenteral nutrition,Heart Association Class III and IV), and if or other medications such as octreotideused at all should be used very cautiously or immunosuppressive medications. (B)in those with, or at risk for, milder degrees IX. DIABETES CARE IN If hyperglycemia is documented andof CHF. Sulfonylureas, other insulin secre- SPECIFIC SETTINGS persistent, consider treating such pa-tagogues, and insulin can cause hypogly- tients to the same glycemic goals as pa-cemia. Insulin use requires that patients or A. Diabetes care in the hospital tients with known diabetes. (E)caregivers have good visual and motor Recommendations c A hypoglycemia management protocolskills and cognitive ability. Drugs should c All patients with diabetes admitted to should be adopted and implementedbe started at the lowest dose and titrated up the hospital should have their diabetes by each hospital or hospital system. Agradually until targets are reached or side clearly identified in the medical record. plan for preventing and treating hypo-effects develop. (E) glycemia should be established for each Screening for diabetes complications c All patients with diabetes should have patient. Episodes of hypoglycemia inin older adults also should be individual- an order for blood glucose monitoring, the hospital should be documented inized. Particular attention should be paid with results available to all members of the medial record and tracked. (E)to complications that can develop over short the health care team. (E) c Consider obtaining an A1C on patientsperiods of time and/or that would signifi- c Goals for blood glucose levels: with diabetes admitted to the hospital ifcantly impair functional status, such as visual the result of testing in the previous 2–3and lower extremity complications. ○ Critically ill patients: Insulin therapy months is not available. (E) should be initiated for treatment of persis- c Patients with hyperglycemia in the hos-D. Cystic fibrosis–related diabetes tent hyperglycemia starting at a threshold of pital who do not have a prior diagnosis(CFRD) no greater than 180 mg/dL (10 mmol/L). of diabetes should have appropriateRecommendations Once insulin therapy is started, a glu- plans for follow-up testing and carec Annual screening for CFRD with OGTT cose range of 140–180 mg/dL (7.8 to 10 documented at discharge. (E) should begin by age 10 years in allS44 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 35. Position Statement Hyperglycemia in the hospital can both surgical and medical patients, as was in hospitalized patients has been defined byrepresent previously known diabetes, mortality from cardiovascular causes. Se- many as ,40 mg/dL (2.2 mmol/L), al-previously undiagnosed diabetes, or vere hypoglycemia was also more common though this is lower than the ;50 mg/dLhospital-related hyperglycemia (fasting in the intensively treated group (6.8% vs. (2.8 mmol/L) level at which cognitive im-blood glucose $126 mg/dL or random 0.5%; P , 0.001). The precise reason for pairment begins in normal individualsblood glucose $200 mg/dL occurring the increased mortality in the tightly con- (420). As with hyperglycemia, hypoglyce-during the hospitalization that reverts trolled group is unknown. The results of mia among inpatients is also associatedto normal after hospital discharge). Hyper- this study lie in stark contrast to a famous with adverse short- and long-term out-glycemia in the hospital is extensively re- 2001 single-center study which reported a comes. Early recognition and treatment ofviewed in an ADA technical review (409). 42% relative reduction in ICU mortality in mild-to-moderate hypoglycemia (40–69An updated consensus statement by the critically ill surgical patients treated to a tar- mg/dL (2.2–3.8 mmol/L) can prevent dete-American Association of Clinical Endocri- get blood glucose of 80–110 mg/dL (411). rioration to a more severe episode with po-nologists (AACE) and ADA (410) forms the Importantly, the control group in NICE- tential adverse sequelae (410).basis for the discussion and guidelines in SUGAR had reasonably good blood glu- Critically ill patients. Based on thethis section. cose management, maintained at a mean weight of the available evidence, for the The management of hyperglycemia in glucose of 144 mg/dL, only 29 mg/dL majority of critically ill patients in the ICUthe hospital has often been considered above the intensively managed patients. setting, insulin infusion should be usedsecondary in importance to the condition Accordingly, this study’s findings do not to control hyperglycemia, with a startingthat prompted admission (409). However, a disprove the notion that glycemic control threshold of no higher than 180 mg/dLbody of literature now supports targeted in the ICU is important. However they do (10.0 mmol/L). Once intravenous insu-glucose control in the hospital setting for strongly suggest that it may not be neces- lin is started, the glucose level should bepotential improved clinical outcomes. Hy- sary to target blood glucose values ,140 maintained between 140 and 180 mg/dLperglycemia in the hospital may result from mg/dL, and that a highly stringent target (7.8–10.0 mmol/L). Greater benefitstress, decompensation of type 1 or type 2 of ,110 mg/dL may actually be dangerous. maybe realized at the lower end of thisor other forms of diabetes, and/or may be In a recent meta-analysis of 26 trials range. Although strong evidence is lack-iatrogenic due to withholding of antihyper- (N 5 13,567), which included the NICE- ing, somewhat lower glucose targetsglycemic medications or administration of SUGAR data, the pooled relative risk (RR) may be appropriate in selected patients.hyperglycemia-provoking agents such as of death with intensive insulin therapy However, targets ,110 mg/dL (6.1glucocorticoids or vasopressors. was 0.93 as compared with conventional mmol/L) are not recommended. Use of There is substantial observational ev- therapy (95% CI 0.83–1.04) (418). Ap- insulin infusion protocols with demon-idence linking hyperglycemia in hospital- proximately half of these trials reported strated safety and efficacy, resulting inized patients (with or without diabetes) to hypoglycemia, with a pooled RR of inten- low rates of hypoglycemia, are highlypoor outcomes. Cohort studies as well as sive therapy of 6.0 (95% CI 4.5–8.0). The recommended (410).a few early RCTs suggested that intensive specific ICU setting influenced the find- Noncritically ill patients. With no pro-treatment of hyperglycemia improved hos- ings, with patients in surgical ICUs ap- spective RCT data to inform specificpital outcomes (409,411,412). In general, pearing to benefit from intensive insulin glycemic targets in noncritically ill patients,these studies were heterogeneous in terms therapy (RR 0.63, 95% CI 0.44–0.91), recommendations are based on clinicalof patient population, blood glucose targets while those in other medical and mixed experience and judgment. For the majorityand insulin protocols used, provision of critical care settings did not. It was con- of noncritically ill patients treated withnutritional support, and the proportion of cluded that, overall, intensive insulin insulin, premeal glucose targets shouldpatients receiving insulin, which limits the therapy increased the risk of hypoglyce- generally be ,140 mg/dL (7.8 mmol/L)ability to make meaningful comparisons mia but provided no overall benefit on with random blood glucose ,180 mg/dLamong them. Recent trials in critically ill mortality in the critically ill, although a (10.0 mmol/L), as long as these targetspatients have failed to show a significant possible mortality benefit to patients ad- can be safely achieved. To avoid hypogly-improvement in mortality with intensive mitted to the surgical ICU was suggested. cemia, consideration should be given toglycemic control (413,414) or have even 1. Glycemic targets in hospitalized reassessing the insulin regimen if bloodshown increased mortality risk (415). patients glucose levels fall ,100 mg/dL (5.6 mmol/Moreover, these recent RCTs have high- Definition of glucose abnormalities in L). Modification of the regimen is requiredlighted the risk of severe hypoglycemia re- the hospital setting. Hyperglycemia in when blood glucose values are ,70 mg/dLsulting from such efforts (413–418). the hospital has been defined as any (3.9 mmol/L), unless the event is easily ex- The largest study to date, NICE- blood glucose .140 mg/dL (7.8 mmol/ plained by other factors (such as a missedSUGAR, a multicenter, multinational RCT, L). Levels that are significantly and per- meal). There is some evidence that system-compared the effect of intensive glycemic sistently above this may require treat- atic attention to hyperglycemia in the emer-control (target 81–108 mg/dL, mean blood ment in hospitalized patients. A1C gency room leads to better glycemic controlglucose attained 115 mg/dL) to standard values .6.5% suggest, in undiagnosed in the hospital for those subsequently admit-glycemic control (target 144–180 mg/dL, patients, that diabetes preceded hospital- ted (421).mean blood glucose attained 144 mg/dL) ization (419). Hypoglycemia has been de- Occasional patients with a prior his-on outcomes among 6,104 critically ill par- fined as any blood glucose ,70 mg/dL tory of successful tight glycemic controlticipants, almost all of whom required me- (3.9 mmol/L). This is the standard defini- in the outpatient setting who are clini-chanical ventilation (415). Ninety-day tion in outpatients and correlates with the cally stable may be maintained with amortality was significantly higher in the in- initial threshold for the release of counter- glucose range below the above cut points.tensive versus the conventional group in regulatory hormones. Severe hypoglycemia Conversely, higher glucose ranges may becare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S45
  • 36. Position Statementacceptable in terminally ill patients or in insufficiency, unstable hemodynamic sta- consciousness, have reasonably stablepatients with severe comorbidities, as well tus, or need for an imaging study that daily insulin requirements, successfullyas in those in patient-care settings where requires a radio-contrast dye. conduct self-management of diabetes atfrequent glucose monitoring or close nurs- 3. Preventing hypoglycemia home, have physical skills needed toing supervision is not feasible. In the hospital, multiple risk factors for successfully self-administer insulin and Clinical judgment, combined with hypoglycemia are present. Patients with or perform SMBG, have adequate oral in-ongoing assessment of the patient’s clini- without diabetes may experience hypogly- take, are proficient in carbohydratecal status, including changes in the trajec- cemia in the hospital in association with counting, use multiple daily insulin in-tory of glucose measures, the severity of altered nutritional state, heart failure, renal jections or insulin pump therapy, and em-illness, nutritional status, or concurrent use or liver disease, malignancy, infection, or ploy sick-day management. The patientof medications that might affect glucose sepsis. Additional triggering events leading and physician, in consultation with nurs-levels (e.g., steroids, octreotide), must be to iatrogenic hypoglycemia include sudden ing staff, must agree that patient self-incorporated into the day-to-day decisions reduction of corticosteroid dose, altered management is appropriate under theregarding insulin dosing (410). ability of the patient to report symptoms, conditions of hospitalization.2. Antihyperglycemic agents in hospi- reduction of oral intake, emesis, new n.p.o. Patients who use CSII pump therapytalized patients status, inappropriate timing of short- or in the outpatient setting can be candidatesIn the hospital setting, insulin therapy is rapid-acting insulin in relation to meals, for diabetes self-management in the hos-the preferred method of glycemic control reduction of rate of administration of in- pital, provided that they have the mentalin majority of clinical situations (410). In travenous dextrose, and unexpected inter- and physical capacity to do so (410). Athe ICU, intravenous infusion is the pre- ruption of enteral feedings or parenteral hospital policy and procedures delineat-ferred route of insulin administration. nutrition. ing inpatient guidelines for CSII therapyWhen the patient is transitioned off intra- Despite the preventable nature of are advisable, and availability of hospitalvenous insulin to subcutaneous therapy, many inpatient episodes of hypoglyce- personnel with expertise in CSII therapyprecautions should be taken to prevent mia, institutions are more likely to have is essential. It is important that nursinghyperglycemia escape (422,423). Outside nursing protocols for the treatment of personnel document basal rates and bolusof critical care units, scheduled subcuta- hypoglycemia than for its prevention. doses taken on a regular basis (at leastneous insulin that delivers basal, nutri- Tracking such episodes and analyzing daily).tional, and correction (supplemental) their causes are important quality im- 6. MNT in the hospitalcomponents is preferred. Prolonged ther- provement activities (410). The goals of MNT are to optimize glyce-apy with sliding scale insulin (SSI) as the 4. Diabetes care providers in the mic control, provide adequate calories tosole regimen is ineffective in the majority hospital meet metabolic demands, and create aof patients, increases risk of both hypo- Inpatient diabetes management may be discharge plan for follow-up careglycemia and hyperglycemia, and has re- effectively championed and/or provided (409,429). ADA does not endorse anycently been shown in a randomized trial by primary care physicians, endocrinolo- single meal plan or specified percentagesto be associated with adverse outcomes in gists, intensivists or hospitalists. Involve- of macronutrients, and the term “ADAgeneral surgery patients with type 2 dia- ment of appropriately trained specialists diet” should no longer be used. Currentbetes (424). SSI is potentially dangerous or specialty teams may reduce length of nutrition recommendations advise indi-in type 1 diabetes (410). The reader is re- stay, improve glycemic control, and im- vidualization based on treatment goals,ferred to several recent publications and prove outcomes (410). In the care of di- physiologic parameters, and medicationreviews that describe currently available abetes, implementation of standardized usage. Consistent carbohydrate mealinsulin preparations and protocols and order sets for scheduled and correction- plans are preferred by many hospitals be-provide guidance in use of insulin therapy dose insulin may reduce reliance on cause they facilitate matching the prandialin specific clinical settings including par- sliding-scale management. As hospitals insulin dose to the amount of carbohy-enteral nutrition (425) and enteral tube move to comply with “meaningful use” drate consumed (430). Because of thefeedings and with high-dose glucocorti- regulations for electronic health records, complexity of nutrition issues in thecoid therapy (410). as mandated by the Health Information hospital, a registered dietitian, knowl- There are no data on the safety and Technology Act, efforts should be made edgeable and skilled in MNT, shouldefficacy of oral agents and injectable non- to assure that all components of structured serve as an inpatient team member. Theinsulin therapies such as GLP1 analogs insulin order sets are incorporated into dietitian is responsible for integrating in-and pramlintide in the hospital. They are electronic insulin order sets (426,427). formation about the patient’s clinical con-generally considered to have a limited role A team approach is needed to estab- dition, eating, and lifestyle habits and forin the management of hyperglycemia in lish hospital pathways. To achieve glyce- establishing treatment goals in order toconjunction with acute illness. Continu- mic targets associated with improved determine a realistic plan for nutritionation of these agents may be appropriate hospital outcomes, hospitals will need therapy (431,432).in selected stable patients who are expec- multidisciplinary support to develop in-ted to consume meals at regular intervals, sulin management protocols that effec- 7. Bedside blood glucose monitoringand they may be initiated or resumed in tively and safely enable achievement of Point-of-care (POC) blood glucose mon-anticipation of discharge once the patient glycemic targets (428). itoring performed at the bedside is used tois clinically stable. Specific caution is re- 5. Self-management in the hospital guide insulin dosing. In the patient who isquired with metformin due to the possi- Self-management of diabetes in the hos- receiving nutrition, the timing of glucosebility that a contraindication may develop pital may be appropriate for competent monitoring should match carbohydrateduring the hospitalization, such as renal adult patients who have a stable level of exposure. In the patient who is notS46 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 37. Position Statementreceiving nutrition, glucose monitoring is Inpatients may be discharged to var- enable safe care at home. Patients hospi-performed every 4 to 6 h (433,434). More- ied settings, including home (with or talized because of a crisis related to diabe-frequent blood glucose testing ranging without visiting nurse services), assisted tes management or poor care at homefrom every 30 min to every 2 h is required living, rehabilitation, or skilled nursing need education to prevent subsequent ep-for patients on intravenous insulin infu- facilities. The latter two sites are generally isodes of hospitalization. An assessmentsions. staffed by health professionals, so diabe- of the need for a home health referral or Safety standards should be estab- tes discharge planning will be limited to referral to an outpatient diabetes educa-lished for blood glucose monitoring pro- communication of medication and diet tion program should be part of dischargehibiting sharing of fingerstick lancing orders. For the patient who is discharged planning for all patients.devices, lancets, needles, and meters to to assisted living or to home, the optimal DSME cannot wait until discharge,reduce the risk of transmission of blood program will need to consider the type especially in those new to insulin therapyborne diseases. Shared lancing devices carry and severity of diabetes, the effects of the or in whom the diabetes regimen has beenessentially the same risk as is conferred from patient’s illness on blood glucose levels, substantially altered during the hospital-sharing of syringes and needles (435). and the capacities and desires of the pa- ization. Accuracy of blood glucose measure- tient. Smooth transition to outpatient It is recommended that the followingments using POC meters has limitations care should be ensured. The Agency for areas of knowledge be reviewed andthat must be considered. Although the Healthcare Research and Quality recom- addressed prior to hospital discharge:FDA allows a 1/2 20% error for blood mends that at a minimum, dischargeglucose meters, questions about the ap- plans include: c Identification of health care providerpropriateness of these criteria have been who will provide diabetes care afterraised (388). Glucose measures differ sig- c Medication reconciliation: The patient’s dischargenificantly between plasma and whole medications must be cross-checked to c Level of understanding related to theblood, terms that are often used inter- ensure that no chronic medications diagnosis of diabetes, SMBG, and ex-changeably and can lead to misinterpreta- were stopped and to ensure the safety of planation of home blood glucose goalstion. Most commercially available capillary new prescriptions. c Definition, recognition, treatment, andblood glucose meters introduce a correc- c Whenever possible, prescriptions for prevention of hyperglycemia and hy-tion factor of ;1.12 to report a “plasma new or changed medication should be poglycemiaadjusted” value (436). filled and reviewed with the patient and c Information on consistent eating pat- Significant discrepancies between family at or before discharge. ternscapillary, venous, and arterial plasma sam- c Structured discharge communication: c When and how to take blood glucose–ples have been observed in patients with Information on medication changes, lowering medications including insulinlow or high hemoglobin concentrations, pending tests and studies, and follow- administration (if going home on in-hypoperfusion, and the presence of in- up needs must be accurately and sulin)terfering substances, particularly maltose, promptly communicated to outpatient c Sick-day managementas contained in immunoglobulins (437). physicians. c Proper use and disposal of needles andAnalytical variability has been described c Discharge summaries should be trans- syringeswith several POC meters (438). Increas- mitted to the primary physician as sooningly newer generation POC blood glu- as possible after discharge. It is important that patients be pro-cose meters correct for variation in c Appointment-keeping behavior is en- vided with appropriate durable medicalhematocrit and for interfering substances. hanced when the inpatient team sched- equipment, medication, supplies, and pre-Any glucose result that does not correlate ules outpatient medical follow up prior scriptions at the time of discharge in orderwith the patient’s status should be con- to discharge. Ideally the inpatient care to avoid a potentially dangerous hiatus infirmed through conventional laboratory providers or case managers/discharge care. These supplies/prescriptions shouldsampling of plasma glucose. The FDA planners will schedule follow-up visit include:has become increasingly concerned about (s) with the appropriate professionals,the use of POC blood glucose meters in including the primary care provider, c Insulin (vials or pens) if neededthe hospital and is presently reviewing endocrinologist, and diabetes educator c Syringes or pen needles (if needed)matters related to their use. (99). c Oral medications (if needed)8. Discharge planning and DSME c Blood glucose meter and stripsTransition from the acute care setting is a Teaching diabetes self-management c Lancets and lancing devicehigh risk time for all patients, not just to patients in hospitals is a challenging c Urine ketone strips (type 1)those with diabetes or new hyperglyce- task. Patients are ill, under increased c Glucagon emergency kit (insulin-treated)mia. Although there is an extensive liter- stress related to their hospitalization and c Medical alert application/charmature concerning safe transition within diagnosis, and in an environment notand from the hospital, little of it is specific conducive to learning. Ideally, people More expanded diabetes educationto diabetes (439). It is important to re- with diabetes should be taught at a time can be arranged in the community. Anmember that diabetes discharge planning and place conducive to learningdas an outpatient follow-up visit with the pri-is not a separate entity, but is part of an outpatient in a recognized program of di- mary care provider, endocrinologist, oroverall discharge plan. As such, discharge abetes education. For the hospitalized pa- diabetes educator within 1 month ofplanning begins at admission to the hos- tient, diabetes “survival skills” education discharge is advised for all patients havingpital and is updated as projected patient is generally a feasible approach to provide hyperglycemia in the hospital. Clear com-needs change. sufficient information and training to munication with outpatient providerscare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S47
  • 38. Position Statementeither directly or via hospital discharge The ADA position statement on di- achieving recommended levels of A1C,summaries facilitates safe transitions to abetes and driving (441) recommends blood pressure, and LDL cholesterol inoutpatient care. Providing information against blanket restrictions based on the the last 10 years, both in primary careregarding the cause or the plan for de- diagnosis of diabetes and urges individual settings and in endocrinology practices.termining the cause of hyperglycemia, assessment by a health care professional Mean A1C nationally has declined fromrelated complications and comorbidities, knowledgeable in diabetes if restrictions 7.82% in 1999–2000 to 7.18% in 2004and recommended treatments can assist on licensure are being considered. Pa- based on NHANES data (443). This hasoutpatient providers as they assume on- tients should be evaluated for decreased been accompanied by improvements ingoing care. awareness of hypoglycemia, hypoglyce- lipids and blood pressure control and mia episodes while driving, or severe hy- has led to substantial reductions in end-B. Diabetes and employment poglycemia. Patients with retinopathy or stage microvascular complications inAny person with diabetes, whether insulin- peripheral neuropathy require assessment those with diabetes. Nevertheless intreated or noninsulin treated, should be to determine if those complications inter- some studies only 57.1% of adults witheligible for any employment for which fere with operation of a motor vehicle. diagnosed diabetes achieved an A1Che/she is otherwise qualified. Employ- Health care professionals should be cogni- ,7%, only 45.5% had a blood pressurement decisions should never be based on zant of the potential risk of driving with ,130/80 mmHg, and only 46.5% had ageneralizations or stereotypes regarding diabetes and counsel their patients about total cholesterol ,200 mg/dL, with onlythe effects of diabetes. When questions detecting and avoiding hypoglycemia 12.2% of people with diabetes achievingarise about the medical fitness of a person while driving. all three treatment goals (444). Evidencewith diabetes for a particular job, a health also suggests that progress in risk factorcare professional with expertise in treat- D. Diabetes management in control may be slowing (445). Certain pa-ing diabetes should perform an individ- correctional institutions tient groups, such as those with complexualized assessment. See the ADA position People with diabetes in correctional facil- comorbidities, financial or other socialstatement on diabetes and employment ities should receive care that meets na- hardships, and/or limited English profi-(440). tional standards. Because it is estimated ciency (LEP), may present particular chal- that nearly 80,000 inmates have diabetes, lenges to goal-based care (446,447).C. Diabetes and driving correctional institutions should have Persistent variation in quality of diabetesA large percentage of people with diabetes written policies and procedures for the care across providers and across practicein the U.S. and elsewhere seek a license management of diabetes and for training settings even after adjusting for patientto drive, either for personal or employ- of medical and correctional staff in di- factors indicates that there remains poten-ment purposes. There has been consider- abetes care practices. See the ADA posi- tial for substantial further improvementsable debate whether, and the extent to tion statement on diabetes management in diabetes care.which, diabetes may be a relevant factor in in correctional institutions (442) for fur- While numerous interventions to im-determining the driver ability and eligi- ther discussion. prove adherence to the recommendedbility for a license. standards have been implemented, a ma- People with diabetes are subject to a X. STRATEGIES FOR jor barrier to optimal care is a deliverygreat variety of licensing requirements IMPROVING DIABETES CARE system that too often is fragmented, lacksapplied by both state and federal juris- clinical information capabilities, oftendictions, which may lead to loss of em- Recommendations duplicates services, and is poorly de-ployment or significant restrictions on a c Care should be aligned with compo- signed for the coordinated delivery ofperson’s license. Presence of a medical nents of the Chronic Care Model to en- chronic care. The Chronic Care Modelcondition that can lead to significantly sure productive interactions between a (CCM) has been shown in numerousimpaired consciousness or cognition prepared proactive practice team and an studies to be an effective framework formay lead to drivers being evaluated for informed activated patient. (A) improving the quality of diabetes carefitness to drive. For diabetes, this typi- c When feasible, care systems should (448). The CCM includes six core ele-cally arises when the person has had a support team-based care, community ments for the provision of optimal carehypoglycemic episode behind the wheel, involvement, patient registries, and em- of patients with chronic disease: 1) deliv-even if this did not lead to a motor vehicle bedded decision support tools to meet ery system design (moving from a reactiveaccident. patient needs (B). to a proactive care delivery system where Epidemiologic and simulator data c Treatment decisions should be timely planned visits are coordinated through asuggest that people with insulin-treated and based on evidence-based guidelines team based approach), 2) self-managementdiabetes have a small increase in risk of that are tailored to individual patient support, 3) decision support (basingmotor vehicle accidents, primarily due to preferences, prognoses, and comorbid- care on evidence-based, effective carehypoglycemia and decreased awareness ities. (B) guidelines), 4) clinical information sys-of hypoglycemia. This increase (RR 1.12– c A patient-centered communication style tems (using registries that can provide1.19) is much smaller than the risks asso- should be employed that incorporates patient-specific and population-basedciated with teenage male drivers (RR 42), patient preferences, assesses literacy and support to the care team), 5) communitydriving at night (RR 142), driving on rural numeracy, and addresses cultural bar- resources and policies (identifying or de-roads compared with urban roads (RR 9.2), riers to care. (B) veloping resources to support healthyand obstructive sleep apnea (RR 2.4), all lifestyles), and 6) health systems (toof which are accepted for unrestricted li- There has been steady improvement create a quality-oriented culture). Redef-censure. in the proportion of diabetes patients inition of the roles of the clinic staff andS48 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 39. Position Statementpromoting self-management on the part approach that includes clinical content diabetes. Diabetes Care 2009;32:1327–of the patient are fundamental to the suc- and skills and behavioral strategies (goal- 1334cessful implementation of the CCM setting, problem solving) and addresses 7. Ziemer DC, Kolm P, Weintraub WS,(449). Collaborative, multidisciplinary emotional concerns in each needed curric- et al. Glucose-independent, black-white differences in hemoglobin A1c levels:teams are best suited to provide such ulum content area. a cross-sectional analysis of 2 studies.care for people with chronic conditions Ann Intern Med 2010;152:770–777like diabetes and to facilitate patients’ per- Objective 3: Change the system 8. Kumar PR, Bhansali A, Ravikiran M, et al.formance of appropriate self-management of care Utility of glycated hemoglobin in di-(148,150,450,451). The most successful practices have an agnosing type 2 diabetes mellitus: a NDEP maintains an online resource institutional priority for providing high community-based study. J Clin Endo-(www.betterdiabetescare.nih.gov) to help quality of care (465). Changes that have crinol Metab 2010;95:2832–2835health care professionals design and im- been shown to increase quality of diabetes 9. Selvin E, Steffes MW, Ballantyne CM,plement more effective health care deliv- care include basing care on evidence- Hoogeveen RC, Coresh J, Brancati FL.ery systems for those with diabetes. Three Racial differences in glycemic markers: based guidelines (466), expanding the a cross-sectional analysis of community-specific objectives, with references to lit- role of teams and staff (449,467), rede- based data. Ann Intern Med 2011;154:erature that outline practical strategies to signing the processes of care (468,469), 303–309achieve each, are below. implementing electronic health record 10. Nowicka P, Santoro N, Liu H, et al. Utility tools (470,471), activating and educating of hemoglobin A(1c) for diagnosing pre-Objective 1: Optimize provider and patients (472,473), and identifying and/ diabetes and diabetes in obese childrenteam behavior or developing and engaging community and adolescents. Diabetes Care 2011;34:The care team should prioritize timely resources and public policy that support 1306–1311and appropriate intensification of lifestyle healthy lifestyles (474). Recent initiatives 11. Cowie CC, Rust KF, Byrd-Holt DD, et al.and/or pharmaceutical therapy of patients such as the Patient Centered Medical Prevalence of diabetes and high risk forwho have not achieved beneficial levels of diabetes using A1C criteria in the U.S. Home show promise to improve outcomes population in 1988-2006. Diabetes Careblood pressure, lipid, or glucose control through coordinated primary care and of- 2010;33:562–568(452). Strategies such as explicit goal set- fer new opportunities for team-based 12. Expert Committee on the Diagnosis andting with patients (453); identifying and chronic disease care (475). Alterations in Classification of Diabetes Mellitus. Re-addressing language, numeracy, or cul- reimbursement that reward the provision port of the Expert Committee on thetural barriers to care (454–456); integrat- of appropriate and high quality care rather Diagnosis and Classification of Diabetesing evidence-based guidelines and clinical than visit-based billing (476), and that can Mellitus. Diabetes Care 1997;20:1183–1197information tools into the process of care accommodate the need to personalize care 13. Genuth S, Alberti KG, Bennett P, et al.;(457–459); and incorporating care man- goals, may provide additional incentives to Expert Committee on the Diagnosis andagement teams including nurses, pharma- improve diabetes care (477). Classification of Diabetes Mellitus. Follow-cists, and other providers (460–463) have up report on the diagnosis of diabetes It is clear that optimal diabetes man- mellitus. Diabetes Care 2003;26:3160–each been shown to optimize provider agement requires an organized, systematic 3167and team behavior and thereby catalyze approach and involvement of a coordi- 14. Zhang X, Gregg EW, Williamson DF,reduction in A1C, blood pressure, and nated team of dedicated health care pro- et al. A1C level and future risk of di-LDL cholesterol. fessionals working in an environment abetes: a systematic review. Diabetes Care where patient-centered high quality care 2010;33:1665–1673Objective 2: Support patient behavior is a priority. 15. Selvin E, Steffes MW, Zhu H, et al.change Glycated hemoglobin, diabetes, and car-Successful diabetes care requires a sys- diovascular risk in nondiabetic adults.tematic approach to supporting patients’ References N Engl J Med 2010;362:800–811behavior change efforts, including (a) 1. 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Diabetes Prevention Study. Lancet 2006; N Engl J Med 2001;344:1343–1350 Hyperglycemia and adverse pregnancy 368:1673–1679 22. Pan XR, Li GW, Hu YH, et al. Effects of outcomes. N Engl J Med 2008;358: 43. Knowler WC, Fowler SE, Hamman RF, diet and exercise in preventing NIDDM 1991–2002 et al.; Diabetes Prevention Program Re- in people with impaired glucose toler- 33. Metzger BE, Gabbe SG, Persson B, et al.; search Group. 10-year follow-up of di- ance. The Da Qing IGT and Diabetes International Association of Diabetes and abetes incidence and weight loss in the Study. Diabetes Care 1997;20:537–544 Pregnancy Study Groups Consensus Panel. Diabetes Prevention Program Outcomes 23. Buchanan TA, Xiang AH, Peters RK, International association of diabetes and Study. Lancet 2009;374:1677–1686 et al. Preservation of pancreatic beta-cell pregnancy study groups recommenda- 44. 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Ackermann RT, Finch EA, Brizendine E, tolerance or impaired fasting glucose: a spective study on pregnancy outcome. Zhou H, Marrero DG. Translating the randomised controlled trial. Lancet 2006; Diabet Med 2011;28:1074–1077 Diabetes Prevention Program into the 368:1096–1105 36. Landon MB, Spong CY, Thom E, et al.; community. The DEPLOY Pilot Study. 26. Ramachandran A, Snehalatha C, Mary S, Eunice Kennedy Shriver National Institute Am J Prev Med 2008;35:357–363 Mukesh B, Bhaskar AD, Vijay V; Indian of Child Health and Human Development 47. Nathan DM, Davidson MB, DeFronzo RA, Diabetes Prevention Programme (IDPP). Maternal-Fetal Medicine Units Network. et al.; American Diabetes Association. The Indian Diabetes Prevention Pro- A multicenter, randomized trial of treat- Impaired fasting glucose and impaired gramme shows that lifestyle modification ment for mild gestational diabetes. 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Committee on Obstetric Practice. Com- women with a history of gestational di- 311 mittee opinion no. 504: screening and abetes: effects of metformin and lifestyle 28. Dabelea D, D’Agostino RB Jr, Mayer- diagnosis of gestational diabetes melli- interventions. J Clin Endocrinol Metab Davis EJ, et al.; SEARCH for Diabetes in tus. Obstet Gynecol 2011;118:751–753 2008;93:4774–4779 Youth Study Group. Testing the accel- 39. Kim C, Herman WH, Cheung NW, 50. Ziegler R, Heidtmann B, Hilgard D, erator hypothesis: body size, beta-cell Gunderson EP, Richardson C. Compar- Hofer S, Rosenbauer J, Holl R; DPV-Wiss- function, and age at onset of type 1 ison of hemoglobin A1c with fasting Initiative. Frequency of SMBG correlates (autoimmune) diabetes. Diabetes Care plasma glucose and 2-h postchallenge with HbA1c and acute complications in 2006;29:290–294 glucose for risk stratification among children and adolescents with type 1 di- 29. 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Di- term effect of lifestyle interventions to in the management of patients with non- abetes Care 2000;23:381–389 prevent diabetes in the China Da Qing insulin treated diabetes: open parallelS50 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 41. Position Statement group randomised trial. BMJ 2007;335: glycemic control in type 1 and insulin- with sulphonylureas or insulin com- 132 treated type 2 diabetic patients. Diabetes pared with conventional treatment and 53. O’Kane MJ, Bunting B, Copeland M, Care 1999;22:1785–1789 risk of complications in patients with Coates VE; ESMON study group. Effi- 64. Miller CD, Barnes CS, Phillips LS, et al. type 2 diabetes (UKPDS 33). Lancet 1998; cacy of self monitoring of blood glucose Rapid A1c availability improves clinical 352:837–853 in patients with newly diagnosed type 2 decision-making in an urban primary care 75. Holman RR, Paul SK, Bethel MA, Matthews diabetes (ESMON study): randomised clinic. Diabetes Care 2003;26:1158–1163 DR, Neil HA. 10-year follow-up of in- controlled trial. BMJ 2008;336:1174–1177 65. Al-Ansary L, Farmer A, Hirst J, et al. tensive glucose control in type 2 diabetes. 54. Simon J, Gray A, Clarke P, Wade A, Neil A, Point-of-care testing for Hb A1c in the N Engl J Med 2008;359:1577–1589 Farmer A; Diabetes Glycaemic Education management of diabetes: a systematic re- 76. Duckworth W, Abraira C, Moritz T, et al.; and Monitoring Trial Group. Cost effec- view and metaanalysis. Clin Chem 2011; VADT Investigators. Glucose control and tiveness of self monitoring of blood glu- 57:568–576 vascular complications in veterans with cose in patients with non-insulin treated 66. Gialamas A, St John A, Laurence CO, type 2 diabetes. N Engl J Med 2009;360: type 2 diabetes: economic evaluation of Bubner TK; PoCT Management Com- 129–139 data from the DiGEM trial. BMJ 2008;336: mittee. Point-of-care testing for patients 77. Moritz T, Duckworth W, Abraira C. Vet- 1177–1180 with diabetes, hyperlipidaemia or co- erans Affairs diabetes trialdcorrections. 55. Sacks DB, Bruns DE, Goldstein DE, agulation disorders in the general prac- N Engl J Med 2009;361:1024–1025 Maclaren NK, McDonald JM, Parrott M. tice setting: a systematic review. Fam 78. Patel A, MacMahon S, Chalmers J, et al.; Guidelines and recommendations for Pract 2010;27:17–24 ADVANCE Collaborative Group. Inten- laboratory analysis in the diagnosis and 67. Nathan DM, Kuenen J, Borg R, Zheng H, sive blood glucose control and vascular management of diabetes mellitus. Clin Schoenfeld D, Heine RJ; A1c-Derived outcomes in patients with type 2 dia- Chem 2002;48:436–472 Average Glucose Study Group. Trans- betes. N Engl J Med 2008;358:2560– 56. Tamborlane WV, Beck RW, Bode BW, lating the A1C assay into estimated av- 2572 et al.; Juvenile Diabetes Research Foun- erage glucose values. Diabetes Care 2008; 79. Ismail-Beigi F, Craven T, Banerji MA, dation Continuous Glucose Monitoring 31:1473–1478 et al.; ACCORD trial group. Effect of Study Group. Continuous glucose mon- 68. Rohlfing CL, Wiedmeyer HM, Little RR, intensive treatment of hyperglycaemia itoring and intensive treatment of type 1 England JD, Tennill A, Goldstein DE. on microvascular outcomes in type 2 diabetes. N Engl J Med 2008;359:1464– Defining the relationship between plasma diabetes: an analysis of the ACCORD 1476 glucose and HbA(1c): analysis of glucose randomised trial. Lancet 2010;376:419– 57. Beck RW, Hirsch IB, Laffel L, et al.; Ju- profiles and HbA(1c) in the Diabetes 430 venile Diabetes Research Foundation Control and Complications Trial. Diabetes 80. Chew EY, Ambrosius WT, Davis MD, Continuous Glucose Monitoring Study Care 2002;25:275–278 et al.; ACCORD Study Group; ACCORD Group. The effect of continuous glucose 69. Wilson DM, Kollman; Diabetes Research Eye Study Group. Effects of medical ther- monitoring in well-controlled type 1 in Children Network (DirecNet) Study apies on retinopathy progression in type diabetes. Diabetes Care 2009;32:1378– Group. Relationship of A1C to glucose 2 diabetes. N Engl J Med 2010;363:233– 1383 concentrations in children with type 1 244 58. Battelino T, Phillip M, Bratina N, Nimri R, diabetes: assessments by high-frequency 81. Gerstein HC, Miller ME, Byington RP, Oskarsson P, Bolinder J. Effect of contin- glucose determinations by sensors. Di- et al.; Action to Control Cardiovascular uous glucose monitoring on hypoglyce- abetes Care 2008;31:381–385 Risk in Diabetes Study Group. Effects of mia in type 1 diabetes. Diabetes Care 70. The Diabetes Control and Complications intensive glucose lowering in type 2 di- 2011;34:795–800 Trial/Epidemiology of Diabetes Inter- abetes. N Engl J Med 2008;358:2545–2559 59. Bergenstal RM, Tamborlane WV, Ahmann ventions and Complications Research 82. Nathan DM, Cleary PA, Backlund JY, A, et al.; STAR 3 Study Group. Effective- Group. Retinopathy and nephropathy in et al.; Diabetes Control and Complica- ness of sensor-augmented insulin-pump patients with type 1 diabetes four years tions Trial/Epidemiology of Diabetes In- therapy in type 1 diabetes. N Engl J Med after a trial of intensive therapy. N Engl terventions and Complications (DCCT/ 2010;363:311–320 J Med 2000;342:381–389 EDIC) Study Research Group. Intensive 60. Slover RH, Welsh JB, Criego A, 71. Martin CL, Albers J, Herman WH, et al.; diabetes treatment and cardiovascular Weinzimer SA, Willi SM, Wood MA, DCCT/EDIC Research Group. Neurop- disease in patients with type 1 diabetes. Tamborlane WV: Effectiveness of sensor- athy among the diabetes control and N Engl J Med 2005;353:2643–2653 augmented pump therapy in children complications trial cohort 8 years after 83. Nathan DM, Zinman B, Cleary PA, et al.; and adolescents with type 1 diabetes in trial completion. Diabetes Care 2006;29: Diabetes Control and Complications Trial/ the STAR 3 study. Pediatr Diabetes. 3 340–344 Epidemiology of Diabetes Interventions July 2011 [Epub ahead of print] 72. Ohkubo Y, Kishikawa H, Araki E, et al. and Complications (DCCT/EDIC) Re- 61. The Diabetes Control and Complications Intensive insulin therapy prevents the search Group. Modern-day clinical course Trial Research Group. The effect of in- progression of diabetic microvascular of type 1 diabetes mellitus after 30 years’ tensive treatment of diabetes on the de- complications in Japanese patients with duration: the diabetes control and com- velopment and progression of long-term non-insulin-dependent diabetes melli- plications trial/epidemiology of diabetes complications in insulin-dependent di- tus: a randomized prospective 6-year interventions and complications and Pitts- abetes mellitus. N Engl J Med 1993;329: study. Diabetes Res Clin Pract 1995;28: burgh epidemiology of diabetes complica- 977–986 103–117 tions experience (1983-2005). Arch Intern 62. Stratton IM, Adler AI, Neil HA, et al. 73. UK Prospective Diabetes Study (UKPDS) Med 2009;169:1307–1316 Association of glycaemia with macro- Group. Effect of intensive blood-glucose 84. Skyler JS, Bergenstal R, Bonow RO, et al.; vascular and microvascular complications control with metformin on complica- American Diabetes Association; Ameri- of type 2 diabetes (UKPDS 35): prospec- tions in overweight patients with type 2 can College of Cardiology Foundation; tive observational study. BMJ 2000;321: diabetes (UKPDS 34). Lancet 1998;352: American Heart Association. Intensive 405–412 854–865 glycemic control and the prevention of 63. Cagliero E, Levina EV, Nathan DM. Im- 74. UK Prospective Diabetes Study (UKPDS) cardiovascular events: implications of the mediate feedback of HbA1c levels improves Group. Intensive blood-glucose control ACCORD, ADVANCE, and VA diabetescare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S51
  • 42. Position Statement trials: a position statement of the American mellitus: scientific review. JAMA 2003; and educator discipline on glycemic Diabetes Association and a scientific 289:2254–2264 control outcomes in the Indian health statement of the American College of 96. Rosenstock J, Dailey G, Massi-Benedetti service. Diabetes Care 2003;26:2500– Cardiology Foundation and the American M, Fritsche A, Lin Z, Salzman A. Re- 2504 Heart Association. Diabetes Care 2009;32: duced hypoglycemia risk with insulin 107. Graber AL, Elasy TA, Quinn D, Wolff K, 187–192 glargine: a meta-analysis comparing in- Brown A. Improving glycemic control in 85. Gerstein HC, Miller ME, Genuth S, et al.; sulin glargine with human NPH insulin adults with diabetes mellitus: shared re- ACCORD Study Group. Long-term ef- in type 2 diabetes. Diabetes Care 2005; sponsibility in primary care practices. fects of intensive glucose lowering on 28:950–955 South Med J 2002;95:684–690 cardiovascular outcomes. 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  • 43. Position Statement with the Mediterranean diet: results of the 128. Turner-McGrievy GM, Barnard ND, children diagnosed with type 1 diabetes PREDIMED-Reus Nutrition Intervention Cohen J, Jenkins DJ, Gloede L, Green through intensive screening and follow- Randomized Trial. Diabetes Care 2010; AA. Changes in nutrient intake and di- up. Diabetes Care 2004;27:1399–1404 34:14-9 etary quality among participants with 141. Heinrich ESNCadVNK. Self-management119. Malik VS, Popkin BM, Bray GA, Després type 2 diabetes following a low-fat vegan interventions for type 2 diabetes: a sys- JP, Willett WC, Hu FB. Sugar-sweetened diet or a conventional diabetes diet for tematic review. Eur Diabetes Nurs 2010; beverages and risk of metabolic syndrome 22 weeks. J Am Diet Assoc 2008;108: 7:71–76 and type 2 diabetes: a meta-analysis. Di- 1636–1645 142. Cochran J, Conn VS. Meta-analysis of abetes Care 2010;33:2477–2483 129. Institute of Medicine. DIetary Reference quality of life outcomes following di-120. Klein S, Sheard NF, Pi-Sunyer X, et al.; Intakes: Energy, Carbohydrate, Fiber, Fat, abetes self-management training. Dia- American Diabetes Association; North Fatty Acids, Cholesterol, Protein, and Amino betes Educ 2008;34:815–823 American Association for the Study of Acids. Washington, D.C., National Acad- 143. Fisher EB, Thorpe CT, Devellis BM, Devellis Obesity; American Society for Clinical emies Press, 2002 RF. Healthy coping, negative emotions, and Nutrition. Weight management through 130. Franz MJ, Bantle JP, Beebe CA, et al. diabetes management: a systematic review lifestyle modification for the prevention Evidence-based nutrition principles and and appraisal. Diabetes Educ 2007;33: and management of type 2 diabetes: ra- recommendations for the treatment and 1080–1103; discussion 1104–1106 tionale and strategies: a statement of prevention of diabetes and related com- 144. Robbins JM, Thatcher GE, Webb DA, the American Diabetes Association, the plications. Diabetes Care 2002;25:148– Valdmanis VG. Nutritionist visits, di- North American Association for the 198 abetes classes, and hospitalization rates Study of Obesity, and the American So- 131. Norris SL, Engelgau MM, Narayan KM. and charges: the Urban Diabetes Study. ciety for Clinical Nutrition. Diabetes Effectiveness of self-management train- Diabetes Care 2008;31:655–660 Care 2004;27:2067–2073 ing in type 2 diabetes: a systematic re- 145. Polonsky WH, Earles J, Smith S, et al.121. Norris SL, Zhang X, Avenell A, et al. Ef- view of randomized controlled trials. Integrating medical management with ficacy of pharmacotherapy for weight Diabetes Care 2001;24:561–587 diabetes self-management training: a ran- loss in adults with type 2 diabetes mel- 132. Norris SL, Lau J, Smith SJ, Schmid CH, domized control trial of the Diabetes Out- litus: a meta-analysis. Arch Intern Med Engelgau MM. Self-management educa- patient Intensive Treatment program. 2004;164:1395–1404 tion for adults with type 2 diabetes: a meta- Diabetes Care 2003;26:3048–3053122. Wolf AM, Conaway MR, Crowther JQ, analysis of the effect on glycemic control. 146. Anderson RM, Funnell MM, Nwankwo et al.; Improving Control with Activity Diabetes Care 2002;25:1159–1171 R, Gillard ML, Oh M, Fitzgerald JT. and Nutrition (ICAN) Study. Translating 133. Gary TL, Genkinger JM, Guallar E, Evaluating a problem-based empower- lifestyle intervention to practice in obese Peyrot M, Brancati FL. Meta-analysis of ment program for African Americans patients with type 2 diabetes: Improving randomized educational and behavioral with diabetes: results of a randomized Control with Activity and Nutrition interventions in type 2 diabetes. Diabetes controlled trial. Ethn Dis 2005;15:671–678 (ICAN) study. Diabetes Care 2004;27: Educ 2003;29:488–501 147. Brown SA, Blozis SA, Kouzekanani K, 1570–1576 134. 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Patient Educ Couns 2004;52: results of a randomized controlled trial. disease risk factors in individuals with 97–105 Diabetes Educ 2010;36:301–309 type 2 diabetes: one-year results of the 136. Warsi A, Wang PS, LaValley MP, Avorn J, 149. Tang TS, Funnell MM, Brown MB, look AHEAD trial. Diabetes Care 2007; Solomon DH. Self-management education Kurlander JE. Self-management support 30:1374–1383 programs in chronic disease: a systematic in “real-world” settings: an empowerment-125. Wing RR, Look AHEAD Research review and methodological critique of the based intervention. Patient Educ Couns Group. Long-term effects of a lifestyle literature. Arch Intern Med 2004;164: 2010;79:178–184 intervention on weight and cardiovas- 1641–1649 150. Renders CM, Valk GD, Griffin S, Wagner cular risk factors in individuals with type 137. Funnell MM, Brown TL, Childs BP, et al. EH, Eijk JT, Assendelft WJ. Interven- 2 diabetes mellitus: four-year results of National standards for diabetes self- tions to improve the management of the Look AHEAD trial. Arch Intern Med management education. Diabetes Care diabetes mellitus in primary care, out- 2010;170:1566–1575 2007;30:1630–1637 patient and community settings. Co-126. Esposito K, Maiorino MI, Ciotola M, 138. Mulcahy K, Maryniuk M, Peeples M, Peyrot chrane Database Syst Rev 2001 (1): et al. Effects of a Mediterranean-style M, Tomky D, Weaver T, Yarborough P: CD001481 diet on the need for antihyperglycemic Diabetes self-management education core 151. Glazier RH, Bajcar J, Kennie NR, Willson drug therapy in patients with newly di- outcomes measures. Diabetes Educ 2003; K. A systematic review of interventions agnosed type 2 diabetes: a randomized 29:768–784 to improve diabetes care in socially dis- trial. Ann Intern Med 2009;151:306– 139. Glasgow RE, Peeples M, Skovlund SE. advantaged populations. 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  • 44. Position Statement153. Sarkisian CA, Brown AF, Norris KC, 167. Duncan I, Ahmed T, Li QE, et al. As- 180. Lemaster JW, Reiber GE, Smith DG, Wintz RL, Mangione CM. A systematic sessing the value of the diabetes educa- Heagerty PJ, Wallace C. Daily weight- review of diabetes self-care interventions tor. Diabetes Educ 2011;37:638–657 bearing activity does not increase the risk for older, African American, or Latino 168. Boulé NG, Haddad E, Kenny GP, Wells of diabetic foot ulcers. Med Sci Sports adults. Diabetes Educ 2003;29:467–479 GA, Sigal RJ. Effects of exercise on gly- Exerc 2003;35:1093–1099154. Chodosh J, Morton SC, Mojica W, cemic control and body mass in type 2 181. Vinik A, Erbas T. Neuropathy. In Hand- et al. Meta-analysis: chronic disease self- diabetes mellitus: a meta-analysis of book of Exercise in Diabetes. 2nd ed. management programs for older adults. controlled clinical trials. JAMA 2001; Ruderman N, Devlin JT, Kriska A, Eds. 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Diabetes Care 2007; Collegoe of Sports Medicine and the 183. Valensi P, Sachs RN, Harfouche B, et al. 30:2433–2440 American Diabetes Association: joint po- Predictive value of cardiac autonomic157. Anderson DR, Christison-Legay J, Proctor- sition statement. Diabetes Care 2010;33: neuropathy in diabetic patients with or Gray E. Self-management goal setting in a 2692–2696 without silent myocardial ischemia. Di- community health center: the impact of 171. U.S.Department of Health and Human abetes Care 2001;24:339–343 goal attainment on diabetes outcomes. Services. 2008 Physical Activity Guide- 184. Mogensen CE. Nephropathy. In Hand- Diabetes Spectrum 2010;23:97–106 lines for Americans [article online], book of Exercise in Diabetes. 2nd ed.158. Rickheim PL, Weaver TW, Flader JL, 2008. Available from http://www.health. Ruderman N, Devlin JT, Kriska A, Eds. Kendall DM. Assessment of group versus gov/paguidelines/guidelines/default. 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Deakin T, McShane CE, Cade JE, High-intensity resistance training im- ment in primary care patients with Type Williams RD. Group based training for proves glycemic control in older patients 2 diabetes. Diabet Med 2007;24:48–54 self-management strategies in people with type 2 diabetes. Diabetes Care 187. American Diabetes Association. Psycho- with type 2 diabetes mellitus. Cochrane 2002;25:1729–1736 social factors affecting adherence, quality Database Syst Rev 2005 (2):CD003417 174. Castaneda C, Layne JE, Munoz-Orians L, of life, and well-being: helping patients161. Duke SA, Colagiuri S, Colagiuri R. In- et al. A randomized controlled trial of cope. In Medical Management of Type 1 Di- dividual patient education for people resistance exercise training to improve abetes. 5th ed. Kaufman FR, Alexandria, with type 2 diabetes mellitus. Cochrane glycemic control in older adults with VA, American Diabetes Association, 2008, Database Syst Rev 2009 (1):CD005268 type 2 diabetes. Diabetes Care 2002;25: p. 173–193162. Heisler M, Vijan S, Makki F, Piette JD. 2335–2341 188. Anderson RJ, Freedland KE, Clouse RE, Diabetes control with reciprocal peer 175. Sigal RJ, Kenny GP, Wasserman DH, Lustman PJ. The prevalence of comorbid support versus nurse care management: Castaneda-Sceppa C. Physical activity/ depression in adults with diabetes: a meta- a randomized trial. Ann Intern Med exercise and type 2 diabetes. Diabetes analysis. Diabetes Care 2001;24:1069– 2010;153:507–515 Care 2004;27:2518–2539 1078163. Heisler M. Different models to mobilize 176. Church TS, Blair SN, Cocreham S, et al. 189. Harkness E, Macdonald W, Valderas J, peer support to improve diabetes self- Effects of aerobic and resistance training Coventry P, Gask L, Bower P. Identifying management and clinical outcomes: on hemoglobin A1c levels in patients psychosocial interventions that improve evidence, logistics, evaluation consid- with type 2 diabetes: a randomized con- both physical and mental health in pa- erations and needs for future research. trolled trial. JAMA 2010;304:2253–2262 tients with diabetes: a systematic review Fam Pract 2010;27(Suppl 1):i23–i32 177. Bax JJ, Young LH, Frye RL, Bonow RO, and meta-analysis. Diabetes Care 2010;164. Foster G, Taylor SJ, Eldridge SE, Ramsay Steinberg HO, Barrett EJ; ADA. Screen- 33:926–930 J, Griffiths CJ. Self-management educa- ing for coronary artery disease in patients 190. Fisher L, Skaff MM, Mullan JT, et al. tion programmes by lay leaders for with diabetes. Diabetes Care 2007;30: Clinical depression versus distress among people with chronic conditions. Co- 2729–2736 patients with type 2 diabetes: not just a chrane Database Syst Rev 2007 (4): 178. 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  • 45. Position Statement among adults with diabetes in managed 206. Buchwald H, Estok R, Fahrbach K, Banel 219. Chobanian AV, Bakris GL, Black HR, care: the Translating Research Into Ac- D, Sledge I. Trends in mortality in bari- et al.; National Heart, Lung, and Blood tion for Diabetes (TRIAD) study. Di- atric surgery: a systematic review and Institute Joint National Committee on abetes Care 2008;31:273–278 meta-analysis. Surgery 2007;142:621– Prevention, Detection, Evaluation, and193. Katon W, Fan MY, Unützer J, Taylor J, 632; discussion 632–635 Treatment of High Blood Pressure; Na- Pincus H, Schoenbaum M. Depression 207. Sjöström L, Narbro K, Sjöström CD, tional High Blood Pressure Education and diabetes: a potentially lethal com- et al.; Swedish Obese Subjects Study. Program Coordinating Committee. The bination. J Gen Intern Med 2008;23: Effects of bariatric surgery on mortality Seventh Report of the Joint National 1571–1575 in Swedish obese subjects. N Engl J Med Committee on Prevention, Detection,194. Zhang X, Norris SL, Gregg EW, Cheng 2007;357:741–752 Evaluation, and Treatment of High Blood YJ, Beckles G, Kahn HS. Depressive 208. Hoerger TJ, Zhang P, Segel JE, Kahn HS, Pressure: the JNC 7 report. JAMA 2003; symptoms and mortality among persons Barker LE, Couper S. Cost-effectiveness 289:2560–2572 with and without diabetes. Am J Epi- of bariatric surgery for severely obese 220. Bobrie G, Genès N, Vaur L, et al. Is demiol 2005;161:652–660 adults with diabetes. Diabetes Care “isolated home” hypertension as op-195. Rubin RR, Peyrot M. Psychological is- 2010;33:1933–1939 posed to “isolated office” hypertension a sues and treatments for people with di- 209. Makary MA, Clark JM, Shore AD, et al. sign of greater cardiovascular risk? Arch abetes. J Clin Psychol 2001;57:457–478 Medication utilization and annual health Intern Med 2001;161:2205–2211196. Young-Hyman DL, Davis CL. Disor- care costs in patients with type 2 diabetes 221. Sega R, Facchetti R, Bombelli M, et al. dered eating behavior in individuals with mellitus before and after bariatric sur- Prognostic value of ambulatory and diabetes: importance of context, evalua- gery. Arch Surg 2010;145:726–731 home blood pressures compared with tion, and classification. Diabetes Care 210. Keating CL, Dixon JB, Moodie ML, office blood pressure in the general 2010;33:683–689 Peeters A, Playfair J, O’Brien PE. Cost- population: follow-up results from the197. Blonde L, Merilainen M, Karwe V, Raskin efficacy of surgically induced weight loss Pressioni Arteriose Monitorate e Loro P; TITRATE Study Group. Patient- for the management of type 2 diabetes: Associazioni (PAMELA) study. Circula- directed titration for achieving glycaemic a randomized controlled trial. Diabetes tion 2005;111:1777–1783 goals using a once-daily basal insulin Care 2009;32:580–584 222. Lewington S, Clarke R, Qizilbash N, Peto analogue: an assessment of two differ- 211. Maciejewski ML, Livingston EH, Smith R, Collins R; Prospective Studies Col- ent fasting plasma glucose targets - the VA, et al. Survival among high-risk pa- laboration. Age-specific relevance of TITRATE study. Diabetes Obes Metab tients after bariatric surgery. JAMA 2011; usual blood pressure to vascular mor- 2009;11:623–631 305:2419–2426 tality: a meta-analysis of individual data198. Kitabchi AE, Umpierrez GE, Miles JM, 212. Himpens J, Cadière GB, Bazi M, Vouche for one million adults in 61 prospective Fisher JN. Hyperglycemic crises in adult M, Cadière B, Dapri G. Long-term out- studies. Lancet 2002;360:1903–1913 patients with diabetes. Diabetes Care comes of laparoscopic adjustable gastric 223. Stamler J, Vaccaro O, Neaton JD, 2009;32:1335–1343 banding. Arch Surg 2011;146:802–807 Wentworth D. Diabetes, other risk fac-199. Cryer PE. Hypoglycaemia: the limiting 213. Smith SA, Poland GA. Use of influenza tors, and 12-yr cardiovascular mortality factor in the glycaemic management of and pneumococcal vaccines in people with for men screened in the Multiple Risk Type I and Type II diabetes. Diabetologia diabetes. Diabetes Care 2000;23:95–108 Factor Intervention Trial. Diabetes Care 2002;45:937–948 214. Colquhoun AJ, Nicholson KG, Botha JL, 1993;16:434–444200. Whitmer RA, Karter AJ, Yaffe K, Raymond NT. Effectiveness of influenza 224. UK Prospective Diabetes Study Group. Quesenberry CP Jr, Selby JV. Hypogly- vaccine in reducing hospital admissions Tight blood pressure control and risk of cemic episodes and risk of dementia in in people with diabetes. Epidemiol Infect macrovascular and microvascular com- older patients with type 2 diabetes mel- 1997;119:335–341 plications in type 2 diabetes: UKPDS 38. litus. JAMA 2009;301:1565–1572 215. Bridges CB, Fukuda K, Uyeki TM, Cox NJ, BMJ 1998;317:703–713201. Jacobson AM, Musen G, Ryan CM, et al.; Singleton JA; Centers for Disease Control 225. Hansson L, Zanchetti A, Carruthers SG, Diabetes Control and Complications and Prevention, Advisory Committee on et al.; HOT Study Group. Effects of in- Trial/Epidemiology of Diabetes Inter- Immunization Practices. Prevention and tensive blood-pressure lowering and ventions and Complications Study Re- control of influenza. Recommendations of low-dose aspirin in patients with hy- search Group. Long-term effect of diabetes the Advisory Committee on Immunization pertension: principal results of the Hy- and its treatment on cognitive function. N Practices (ACIP). MMWR Recomm Rep pertension Optimal Treatment (HOT) Engl J Med 2007;356:1842–1852 2002;51(RR-3):1–31 randomised trial. Lancet 1998;351:1755–202. Cryer PE. Diverse causes of hypoglycemia- 216. Buse JB, Ginsberg HN, Bakris GL, et al.; 1762 associated autonomic failure in diabetes. N American Heart Association; American 226. 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Effect of a multifactorial in- intensive blood-pressure control in type tional therapy for type 2 diabetes: a ran- tervention on mortality in type 2 diabetes. 2 diabetes mellitus. N Engl J Med 2010; domized controlled trial. JAMA 2008; N Engl J Med 2008;358:580–591 362:1575–1585 299:316–323 218. Ford ES. Trends in the risk for coronary 228. Patel A, MacMahon S, Chalmers J, et al.;205. Hall TC, Pellen MG, Sedman PC, Jain heart disease among adults with di- ADVANCE Collaborative Group. Effects PK. Preoperative factors predicting re- agnosed diabetes in the U.S.: findings of a fixed combination of perindopril mission of type 2 diabetes mellitus after from the National Health and Nutrition and indapamide on macrovascular and Roux-en-Y gastric bypass surgery for Examination Survey, 1999-2008. Di- microvascular outcomes in patients with obesity. Obes Surg 2010;20:1245–1250 abetes Care 2011;34:1337–1343 type 2 diabetes mellitus (the ADVANCEcare.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S55
  • 46. Position Statement trial): a randomised controlled trial. Effects of candesartan on mortality and myocardial infarction survivors with aver- Lancet 2007;370:829–840 morbidity in patients with chronic heart age cholesterol levels: subgroup analyses in229. Cooper-DeHoff RM, Gong Y, Handberg failure: the CHARM-Overall programme. the cholesterol and recurrent events (CARE) EM, et al. Tight blood pressure control Lancet 2003;362:759–766 trial. Circulation 1998;98:2513–2519 and cardiovascular outcomes among 239. Granger CB, McMurray JJ, Yusuf S, et al.; 249. Shepherd J, Barter P, Carmena R, et al. hypertensive patients with diabetes and CHARM Investigators and Committees. Effect of lowering LDL cholesterol sub- coronary artery disease. JAMA 2010; Effects of candesartan in patients with stantially below currently recommended 304:61–68 chronic heart failure and reduced left- levels in patients with coronary heart230. Sacks FM, Svetkey LP, Vollmer WM, ventricular systolic function intolerant disease and diabetes: the Treating to et al.; DASH-Sodium Collaborative Re- to angiotensin-converting-enzyme in- New Targets (TNT) study. Diabetes Care search Group. Effects on blood pres- hibitors: the CHARM-Alternative trial. 2006;29:1220–1226 sure of reduced dietary sodium and the Lancet 2003;362:772–776 250. Sever PS, Poulter NR, Dahlöf B, et al. Dietary Approaches to Stop Hyperten- 240. Lindholm LH, Ibsen H, Dahlöf B, et al.; Reduction in cardiovascular events with sion (DASH) diet. N Engl J Med 2001; LIFE Study Group. Cardiovascular atorvastatin in 2,532 patients with type 344:3–10 morbidity and mortality in patients with 2 diabetes: Anglo-Scandinavian Cardiac231. Tatti P, Pahor M, Byington RP, et al. diabetes in the Losartan Intervention Outcomes Trialdlipid-lowering arm Outcome results of the Fosinopril Versus For Endpoint reduction in hypertension (ASCOT-LLA). Diabetes Care 2005;28: Amlodipine Cardiovascular Events Ran- study (LIFE): a randomised trial against 1151–1157 domized Trial (FACET) in patients with atenolol. Lancet 2002;359:1004–1010 251. Knopp RH, d’Emden M, Smilde JG, hypertension and NIDDM. Diabetes Care 241. Berl T, Hunsicker LG, Lewis JB, et al.; Pocock SJ. Efficacy and safety of ator- 1998;21:597–603 Irbesartan Diabetic Nephropathy Trial. vastatin in the prevention of cardiovas-232. Estacio RO, Jeffers BW, Hiatt WR, Collaborative Study Group. Cardiovas- cular end points in subjects with type Biggerstaff SL, Gifford N, Schrier RW. cular outcomes in the Irbesartan Di- 2 diabetes: the Atorvastatin Study for The effect of nisoldipine as compared abetic Nephropathy Trial of patients Prevention of Coronary Heart Disease with enalapril on cardiovascular outcomes with type 2 diabetes and overt ne- Endpoints in non-insulin-dependent di- in patients with non-insulin-dependent phropathy. Ann Intern Med 2003;138: abetes mellitus (ASPEN). Diabetes Care diabetes and hypertension. N Engl J Med 542–549 2006;29:1478–1485 1998;338:645–652 242. McManus RJ, Mant J, Bray EP, et al. 252. Colhoun HM, Betteridge DJ, Durrington233. Schrier RW, Estacio RO, Mehler PS, Telemonitoring and self-management in PN, et al.; CARDS investigators. Primary Hiatt WR. Appropriate blood pressure the control of hypertension (TASMINH2): prevention of cardiovascular disease control in hypertensive and normoten- a randomised controlled trial. Lancet with atorvastatin in type 2 diabetes in the sive type 2 diabetes mellitus: a summary 2010;376:163–172 Collaborative Atorvastatin Diabetes Study of the ABCD trial. Nat Clin Pract Nephrol 243. Hermida RC, Ayala DE, Mojón A, (CARDS): multicentre randomised placebo- 2007;3:428–438 Fernández JR. Influence of time of day of controlled trial. Lancet 2004;364:685–234. 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J Am Coll Cardiol 1986;8:1245– Lowering Treatment to Prevent Heart At- Collaborators. Efficacy and safety of 1255 tack Trial (ALLHAT). JAMA 2002;288: cholesterol-lowering treatment: pro- 255. Rubins HB, Robins SJ, Collins D, et al.; 2981–2997 spective meta-analysis of data from Veterans Affairs High-Density Lipopro-235. Psaty BM, Smith NL, Siscovick DS, et al. 90,056 participants in 14 randomised tein Cholesterol Intervention Trial Study Health outcomes associated with anti- trials of statins. Lancet 2005;366:1267– Group. Gemfibrozil for the secondary hypertensive therapies used as first-line 1278 prevention of coronary heart disease in agents. A systematic review and meta- 246. ˘ Pyorälä K, Pedersen TR, Kjekshus J, men with low levels of high-density li- analysis. JAMA 1997;277:739–745 Faergeman O, Olsson AG, Thorgeirsson poprotein cholesterol. N Engl J Med236. Heart Outcomes Prevention Evaluation G. Cholesterol lowering with simvastatin 1999;341:410–418 Study Investigators. Effects of ramipril improves prognosis of diabetic patients 256. Frick MH, Elo O, Haapa K, et al. Helsinki on cardiovascular and microvascular with coronary heart disease. A subgroup Heart Study: primary-prevention trial outcomes in people with diabetes mel- analysis of the Scandinavian Simvastatin with gemfibrozil in middle-aged men litus: results of the HOPE study and Survival Study (4S). Diabetes Care 1997; with dyslipidemia. Safety of treatment, MICRO-HOPE substudy. Lancet 2000; 20:614–620 changes in risk factors, and incidence of 355:253–259 247. Collins R, Armitage J, Parish S, Sleigh P, coronary heart disease. N Engl J Med237. McMurray JJ, Ostergren J, Swedberg K, Peto R; Heart Protection Study Collabo- 1987;317:1237–1245 et al.; CHARM Investigators and Com- rative Group. MRC/BHF Heart Protection 257. Keech A, Simes RJ, Barter P, et al.; FIELD mittees. Effects of candesartan in pa- Study of cholesterol-lowering with sim- study investigators. Effects of long-term tients with chronic heart failure and vastatin in 5963 people with diabetes: fenofibrate therapy on cardiovascular reduced left-ventricular systolic function a randomised placebo-controlled trial. events in 9795 people with type 2 diabetes taking angiotensin-converting-enzyme Lancet 2003;361:2005–2016 mellitus (the FIELD study): randomised inhibitors: the CHARM-Added trial. 248. Goldberg RB, Mellies MJ, Sacks FM, et al.; controlled trial. Lancet 2005;366:1849– Lancet 2003;362:767–771 The Care Investigators. Cardiovascular 1861238. Pfeffer MA, Swedberg K, Granger CB, et al.; events and their reduction with pravas- 258. Expert Panel on Detection, Evaluation, CHARM Investigators and Committees. tatin in diabetic and glucose-intolerant and Treatment of High Blood CholesterolS56 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 47. Position Statement in Adults. Executive Summary of The diabetes: results of the assessment of 277. Davì G, Patrono C. Platelet activation Third Report of The National Cholesterol diabetes control and evaluation of the and atherothrombosis. N Engl J Med Education Program (NCEP) Expert Panel efficacy of niaspan trial. Arch Intern Med 2007;357:2482–2494 on Detection, Evaluation, And Treatment 2002;162:1568–1576 278. Bhatt DL, Marso SP, Hirsch AT, Ringleb of High Blood Cholesterol In Adults 268. Jones PH, Davidson MH. Reporting rate PA, Hacke W, Topol EJ. Amplified ben- (Adult Treatment Panel III). JAMA 2001; of rhabdomyolysis with fenofibrate 1 efit of clopidogrel versus aspirin in pa- 285:2486–2497 statin versus gemfibrozil 1 any statin. tients with diabetes mellitus. Am J259. Hayward RA, Hofer TP, Vijan S. Narrative Am J Cardiol 2005;95:120–122 Cardiol 2002;90:625–628 review: lack of evidence for recommended 269. Ginsberg HN, Elam MB, Lovato LC, 279. 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Baigent C, Blackwell L, Collins R, et al.; Am Coll Cardiol 2006;47:65–71 dromes. N Engl J Med 2004;350:1495– Antithrombotic Trialists’ (ATT) Collab- 281. Boden WE, O’Rourke RA, Teo KK, et al.; 1504 oration. Aspirin in the primary and sec- COURAGE Trial Research Group. Opti-261. de Lemos JA, Blazing MA, Wiviott SD, ondary prevention of vascular disease: mal medical therapy with or without PCI et al.; A to Z Investigators. Early intensive collaborative meta-analysis of individual for stable coronary disease. N Engl J Med vs a delayed conservative simvastatin participant data from randomised trials. 2007;356:1503–1516 strategy in patients with acute coronary Lancet 2009;373:1849–1860 282. Frye RL, August P, Brooks MM, et al.; syndromes: phase Z of the A to Z trial. 272. Ogawa H, Nakayama M, Morimoto T, BARI 2D Study Group. A randomized JAMA 2004;292:1307–1316 et al.; Japanese Primary Prevention of trial of therapies for type 2 diabetes and262. Nissen SE, Tuzcu EM, Schoenhagen P, Atherosclerosis With Aspirin for Di- coronary artery disease. N Engl J Med et al.; REVERSAL Investigators. Effect abetes (JPAD) Trial Investigators. Low- 2009;360:2503–2515 of intensive compared with moderate dose aspirin for primary prevention of 283. Wackers FJ, Chyun DA, Young LH, et al.; lipid-lowering therapy on progression of atherosclerotic events in patients with Detection of Ischemia in Asymptomatic coronary atherosclerosis: a randomized type 2 diabetes: a randomized controlled Diabetics (DIAD) Investigators. Resolu- controlled trial. JAMA 2004;291:1071– trial. JAMA 2008;300:2134–2141 tion of asymptomatic myocardial ische- 1080 273. Belch J, MacCuish A, Campbell I, Cobbe mia in patients with type 2 diabetes in263. Grundy SM, Cleeman JI, Merz CN, et al.; S, Taylor R, Prescott R, Lee R, Bancroft J, the Detection of Ischemia in Asymp- National Heart, Lung, and Blood In- MacEwan S, Shepherd J, Macfarlane P, tomatic Diabetics (DIAD) study. Di- stitute; American College of Cardiology Morris A, Jung R, Kelly C, Connacher A, abetes Care 2007;30:2892–2898 Foundation; American Heart Associa- Peden N, Jamieson A, Matthews D, Leese 284. Young LH, Wackers FJ, Chyun DA, et al.; tion. Implications of recent clinical trials G, McKnight J, O’Brien I, Semple C, DIAD Investigators. Cardiac outcomes for the National Cholesterol Education Petrie J, Gordon D, Pringle S, MacWalter after screening for asymptomatic coro- Program Adult Treatment Panel III guide- R: The prevention of progression of ar- nary artery disease in patients with type 2 lines. Circulation 2004;110:227–239 terial disease and diabetes (POPADAD) diabetes: the DIAD study: a randomized264. Chasman DI, Posada D, Subrahmanyan trial: factorial randomised placebo con- controlled trial. JAMA 2009;301:1547– L, Cook NR, Stanton VP Jr, Ridker PM. trolled trial of aspirin and antioxidants in 1555 Pharmacogenetic study of statin therapy patients with diabetes and asymptomatic 285. Hadamitzky M, Hein F, Meyer T, et al. and cholesterol reduction. JAMA 2004; peripheral arterial disease. BMJ 2008; Prognostic value of coronary computed 291:2821–2827 337:a1840 tomographic angiography in diabetic pa-265. Brunzell JD, Davidson M, Furberg CD, 274. Pignone M, Earnshaw S, Tice JA, Pletcher tients without known coronary artery dis- et al.; American Diabetes Association; MJ. Aspirin, statins, or both drugs for ease. Diabetes Care 2010;33:1358–1363 American College of Cardiology Foun- the primary prevention of coronary 286. Elkeles RS, Godsland IF, Feher MD, et al.; dation. Lipoprotein management in heart disease events in men: a cost- PREDICT Study Group. Coronary cal- patients with cardiometabolic risk: con- utility analysis. Ann Intern Med 2006; cium measurement improves prediction sensus statement from the American 144:326–336 of cardiovascular events in asymptomatic Diabetes Association and the American 275. Pignone M, Alberts MJ, Colwell JA, et al.; patients with type 2 diabetes: the PRE- College of Cardiology Foundation. Di- American Diabetes Association; Ameri- DICT study. Eur Heart J 2008;29:2244– abetes Care 2008;31:811–822 can Heart Association; American College 2251266. Elam MB, Hunninghake DB, Davis KB, of Cardiology Foundation. Aspirin for 287. Choi EK, Chun EJ, Choi SI, et al. As- et al. Effect of niacin on lipid and lipo- primary prevention of cardiovascular sessment of subclinical coronary ath- protein levels and glycemic control in events in people with diabetes: a position erosclerosis in asymptomatic patients patients with diabetes and peripheral statement of the American Diabetes with type 2 diabetes mellitus with single arterial disease: the ADMIT study: A Association, a scientific statement of the photon emission computed tomography randomized trial. Arterial Disease Mul- American Heart Association, and an ex- and coronary computed tomography tiple Intervention Trial. JAMA 2000;284: pert consensus document of the Ameri- angiography. Am J Cardiol 2009;104: 1263–1270 can College of Cardiology Foundation. 890–896267. Grundy SM, Vega GL, McGovern ME, Diabetes Care 2010;33:1395–1402 288. Braunwald E, Domanski MJ, Fowler et al.; Diabetes Multicenter Research 276. Campbell CL, Smyth S, Montalescot G, SE, et al.; PEACE Trial Investigators. Group. Efficacy, safety, and tolerability Steinhubl SR. Aspirin dose for the pre- Angiotensin-converting-enzyme inhibition of once-daily niacin for the treatment of vention of cardiovascular disease: a system- in stable coronary artery disease. N Engl J dyslipidemia associated with type 2 atic review. JAMA 2007;297:2018–2024 Med 2004;351:2058–2068care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S57
  • 48. Position Statement289. Yusuf S, Teo K, Anderson C, et al.; Tel- study. J Am Soc Nephrol 2006;17(Suppl 311. Parving HH, Persson F, Lewis JB, Lewis misartan Randomised AssessmeNt Study 2):S90–S97 EJ, Hollenberg NK; AVOID Study In- in ACE iNtolerant subjects with cardio- 300. Haller H, Ito S, Izzo JL Jr, et al.; ROADMAP vestigators. Aliskiren combined with vascular Disease (TRANSCEND) Inves- Trial Investigators. Olmesartan for the losartan in type 2 diabetes and ne- tigators. Effects of the angiotensin-receptor delay or prevention of microalbuminuria phropathy. N Engl J Med 2008;358: blocker telmisartan on cardiovascular in type 2 diabetes. N Engl J Med 2011; 2433–2446 events in high-risk patients intolerant 364:907–917 312. Pijls LT, de Vries H, Donker AJ, van Eijk to angiotensin-converting enzyme in- 301. Bilous R, Chaturvedi N, Sjølie AK, et al. JT. The effect of protein restriction hibitors: a randomised controlled trial. 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BMJ 1997;314: diabetes and nephropathy. N Engl J Med in renal function. Am J Kidney Dis 1998; 783–788 2001;345:861–869 31:954–961293. Ravid M, Lang R, Rachmani R, Lishner 305. Parving HH, Lehnert H, Bröchner- 316. Eknoyan G, Hostetter T, Bakris GL, et al. M. Long-term renoprotective effect of Mortensen J, Gomis R, Andersen S, Proteinuria and other markers of chronic angiotensin-converting enzyme inhibi- Arner P; Irbesartan in Patients with Type kidney disease: a position statement of tion in non-insulin-dependent diabetes 2 Diabetes and Microalbuminuria Study the national kidney foundation (NKF) mellitus. A 7-year follow-up study. Arch Group. The effect of irbesartan on the and the national institute of diabetes and Intern Med 1996;156:286–289 development of diabetic nephropathy in digestive and kidney diseases (NIDDK).294. Reichard P, Nilsson BY, Rosenqvist U. patients with type 2 diabetes. N Engl J Am J Kidney Dis 2003;42:617–622 The effect of long-term intensified in- Med 2001;345:870–878 317. Levey AS, Coresh J, Balk E, et al.; National sulin treatment on the development of 306. Pepine CJ, Handberg EM, Cooper- Kidney Foundation. National Kidney microvascular complications of diabetes DeHoff RM, et al.; INVEST Investigators. Foundation practice guidelines for mellitus. N Engl J Med 1993;329:304– A calcium antagonist vs a non-calcium chronic kidney disease: evaluation, 309 antagonist hypertension treatment strat- classification, and stratification. Ann In-295. The Diabetes Control and Complications egy for patients with coronary artery tern Med 2003;139:137–147 (DCCT) Research Group. Effect of in- disease. The International Verapamil- 318. Kramer H, Molitch ME. Screening for tensive therapy on the development and Trandolapril Study (INVEST): a ran- kidney disease in adults with diabetes. progression of diabetic nephropathy in domized controlled trial. JAMA 2003; Diabetes Care 2005;28:1813–1816 the Diabetes Control and Complications 290:2805–2816 319. Kramer HJ, Nguyen QD, Curhan G, Hsu Trial. Kidney Int 1995;47:1703–1720 307. Bakris GL, Siomos M, Richardson D, CY. Renal insufficiency in the absence of296. Lewis EJ, Hunsicker LG, Bain RP, Rohde et al.; VAL-K Study Group. ACE in- albuminuria and retinopathy among adults RD; The Collaborative Study Group. The hibition or angiotensin receptor block- with type 2 diabetes mellitus. JAMA 2003; effect of angiotensin-converting-enzyme ade: impact on potassium in renal 289:3273–3277 inhibition on diabetic nephropathy. N failure. Kidney Int 2000;58:2084–2092 320. Levey AS, Bosch JP, Lewis JB, Greene T, Engl J Med 1993;329:1456–1462 308. Mogensen CE, Neldam S, Tikkanen I, Rogers N, Roth D; Modification of Diet297. Laffel LM, McGill JB, Gans DJ; North et al. Randomised controlled trial of dual in Renal Disease Study Group. A more American Microalbuminuria Study Group. blockade of renin-angiotensin system accurate method to estimate glomerular The beneficial effect of angiotensin- in patients with hypertension, micro- filtration rate from serum creatinine: converting enzyme inhibition with captopril albuminuria, and non-insulin dependent a new prediction equation. Ann Intern on diabetic nephropathy in normotensive diabetes: the candesartan and lisinopril Med 1999;130:461–470 IDDM patients with microalbuminuria. microalbuminuria (CALM) study. BMJ 321. Rigalleau V, Lasseur C, Perlemoine C, Am J Med 1995;99:497–504 2000;321:1440–1444 et al. Estimation of glomerular filtration298. Bakris GL, Williams M, Dworkin L, et al.; 309. Schjoedt KJ, Jacobsen P, Rossing K, rate in diabetic subjects: Cockcroft for- National Kidney Foundation Hyperten- Boomsma F, Parving HH. Dual blockade mula or modification of Diet in Renal sion and Diabetes Executive Committees of the renin-angiotensin-aldosterone sys- Disease study equation? Diabetes Care Working Group. Preserving renal func- tem in diabetic nephropathy: the role of 2005;28:838–843 tion in adults with hypertension and aldosterone. Horm Metab Res 2005;37 322. Levinsky NG. Specialist evaluation in diabetes: a consensus approach. Am J (Suppl 1):4–8 chronic kidney disease: too little, too Kidney Dis 2000;36:646–661 310. Schjoedt KJ, Rossing K, Juhl TR, et al. late. Ann Intern Med 2002;137:542–543299. Remuzzi G, Macia M, Ruggenenti P. Beneficial impact of spironolactone in 323. Klein R. Hyperglycemia and microvas- Prevention and treatment of diabetic renal diabetic nephropathy. Kidney Int 2005; cular and macrovascular disease in di- disease in type 2 diabetes: the BENEDICT 68:2829–2836 abetes. Diabetes Care 1995;18:258–268S58 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 49. Position Statement324. Estacio RO, McFarling E, Biggerstaff S, 336. Wile DJ, Toth C. Association of metfor- Prevention. Diabetes Res Clin Pract 2008; Jeffers BW, Johnson D, Schrier RW. min, elevated homocysteine, and meth- 81:2–12 Overt albuminuria predicts diabetic ret- ylmalonic acid levels and clinically 348. Clark JM, Brancati FL, Diehl AM. The inopathy in Hispanics with NIDDM. Am worsened diabetic peripheral neuropa- prevalence and etiology of elevated ami- J Kidney Dis 1998;31:947–953 thy. Diabetes Care 2010;33:156–161 notransferase levels in the United States.325. Leske MC, Wu SY, Hennis A, et al.; Bar- 337. Freeman R. Not all neuropathy in di- Am J Gastroenterol 2003;98:960–967 bados Eye Study Group. Hyperglycemia, abetes is of diabetic etiology: differential 349. El-Serag HB, Tran T, Everhart JE. Di- blood pressure, and the 9-year incidence diagnosis of diabetic neuropathy. Curr abetes increases the risk of chronic liver of diabetic retinopathy: the Barbados Eye Diab Rep 2009;9:423–431 disease and hepatocellular carcinoma. Studies. Ophthalmology 2005;112:799– 338. Vinik AI, Maser RE, Mitchell BD, Gastroenterology 2004;126:460–468 805 Freeman R. Diabetic autonomic neu- 350. American Gastroenterological Associa-326. Fong DS, Aiello LP, Ferris FL 3rd, Klein ropathy. Diabetes Care 2003;26:1553– tion. American Gastroenterological As- R. Diabetic retinopathy. Diabetes Care 1579 sociation medical position statement: 2004;27:2540–2553 339. Spallone V, Bellavere F, Scionti L, et al.; nonalcoholic fatty liver disease. Gastro-327. Diabetes Control and Complications Diabetic Neuropathy Study Group of the enterology 2002;123:1702–1704 Trial Research Group. Effect of preg- Italian Society of Diabetology. Recom- 351. Dhindsa S, Miller MG, McWhirter CL, nancy on microvascular complications mendations for the use of cardiovascular et al. Testosterone concentrations in di- in the diabetes control and complica- tests in diagnosing diabetic autonomic abetic and nondiabetic obese men. Di- tions trial. Diabetes Care 2000;23:1084– neuropathy. Nutr Metab Cardiovasc Dis abetes Care 2010;33:1186–1192 1091 2011;21:69–78 352. Bhasin S, Cunningham GR, Hayes FJ,328. The Diabetic Retinopathy Study Re- 340. Boulton AJ, Armstrong DG, Albert SF, et al.; Task Force, Endocrine Society. search Group. Preliminary report on ef- et al.; American Diabetes Association; Testosterone therapy in men with an- fects of photocoagulation therapy. Am American Association of Clinical Endo- drogen deficiency syndromes: an Endo- J Ophthalmol 1976;81:383–396 crinologists. Comprehensive foot exam- crine Society clinical practice guideline. J329. ETDRS. Photocoagulation for diabetic ination and risk assessment: a report of Clin Endocrinol Metab 2010;95:2536– macular edema. Early Treatment Diabetic the task force of the foot care interest 2559 Retinopathy Study report number 1. Early group of the American Diabetes Associa- 353. Khader YS, Dauod AS, El-Qaderi SS, Treatment Diabetic Retinopathy Study tion, with endorsement by the American Alkafajei A, Batayha WQ. Periodontal research group. Arch Ophthalmol 1985; Association of Clinical Endocrinologists. status of diabetics compared with non- 103:1796–1806 Diabetes Care 2008;31:1679–1685 diabetics: a meta-analysis. J Diabetes330. Boyer DS. Ranibizumab (anti-VEGF) for 341. American Diabetes Association. Peripheral Complications 2006;20:59–68 vision loss due to diabetic macular arterial disease in people with diabetes. 354. Darré L, Vergnes JN, Gourdy P, Sixou M. edema: reslts of two phase III random- Diabetes Care 2003;26:3333–3341 Efficacy of periodontal treatment on ized trials. 2011. 342. Bainbridge KE, Hoffman HJ, Cowie CC. glycaemic control in diabetic patients:331. Agardh E, Tababat-Khani P. Adopting Diabetes and hearing impairment in the A meta-analysis of interventional stud- 3-year screening intervals for sight- United States: audiometric evidence ies. Diabetes Metab 2008;34:497–506 threatening retinal vascular lesions in from the National Health and Nutrition 355. International Diabetes Federation. Oral type 2 diabetic subjects without reti- Examination Survey, 1999 to 2004. Ann Health for People with Diabetes. Brussels, nopathy. Diabetes Care 2011;34:1318– Intern Med 2008;149:1–10 International Diabetes Federation, 2009 1319 343. Bainbridge KE, Hoffman HJ, Cowie CC. 356. Suh S, Kim KW. Diabetes and cancer: is332. Fong DS, Aiello L, Gardner TW, et al.; Risk factors for hearing impairment diabetes causally related to cancer? Di- American Diabetes Association. Reti- among U.S. adults with diabetes: Na- abetes Metab J 2011;35:193–198 nopathy in diabetes. Diabetes Care 2004; tional Health and Nutrition Examination 356a. International Diabetes Federation. Oral 27(Suppl 1):S84–S87 Survey 1999-2004. Diabetes Care 2011; Health for Patients with Diabetes.333. Ahmed J, Ward TP, Bursell SE, Aiello 34:1540–1545 Brussels, 2009, International Diabetes LM, Cavallerano JD, Vigersky RA. The 344. Li C, Ford ES, Zhao G, Croft JB, Balluz LS, Federation sensitivity and specificity of nonmydriatic Mokdad AH. Prevalence of self-reported 357. Janghorbani M, Van Dam RM, Willett digital stereoscopic retinal imaging in clinically diagnosed sleep apnea according WC, Hu FB. Systematic review of type detecting diabetic retinopathy. Diabetes to obesity status in men and women: 1 and type 2 diabetes mellitus and risk Care 2006;29:2205–2209 National Health and Nutrition Examina- of fracture. Am J Epidemiol 2007;166:334. Bril V, England J, Franklin GM, et al.; tion Survey, 2005-2006. Prev Med 2010; 495–505 American Academy of Neurology; 51:18–23 358. Vestergaard P. Discrepancies in bone American Association of Neuromuscular 345. West SD, Nicoll DJ, Stradling JR. Preva- mineral density and fracture risk in pa- and Electrodiagnostic Medicine; Ameri- lence of obstructive sleep apnoea in men tients with type 1 and type 2 diabetesda can Academy of Physical Medicine and with type 2 diabetes. Thorax 2006;61: meta-analysis. Osteoporos Int 2007;18: Rehabilitation. Evidence-based guide- 945–950 427–444 line: Treatment of painful diabetic neu- 346. Foster GD, Sanders MH, Millman R, 359. Yamamoto M, Yamaguchi T, Yamauchi ropathy: report of the American Academy et al.; Sleep AHEAD Research Group. M, Kaji H, Sugimoto T. Diabetic patients of Neurology, the American Association Obstructive sleep apnea among obese have an increased risk of vertebral frac- of Neuromuscular and Electrodiagnostic patients with type 2 diabetes. Diabetes tures independent of BMD or diabetic Medicine, and the American Academy of Care 2009;32:1017–1019 complications. J Bone Miner Res 2009; Physical Medicine and Rehabilitation. 347. 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  • 50. Position Statement Association of BMD and FRAX score hyperglycemia-induced injury. J Cereb Obesity in Youth Committee, Council of with risk of fracture in older adults with Blood Flow Metab 2004;24:1393–1399 Cardiovascular Disease in the Young, type 2 diabetes. JAMA 2011;305:2184– 373. Krantz JS, Mack WJ, Hodis HN, Liu CR, with the Council on Cardiovascular 2192 Liu CH, Kaufman FR. Early onset of Nursing. Circulation 2007;115:1948–361. Cukierman T, Gerstein HC, Williamson subclinical atherosclerosis in young 1967 JD. Cognitive decline and dementia in persons with type 1 diabetes. J Pediatr 379. Salo P, Viikari J, Hämäläinen M, et al. diabetesdsystematic overview of pro- 2004;145:452–457 Serum cholesterol ester fatty acids in 7- and spective observational studies. Dia- 374. Järvisalo MJ, Putto-Laurila A, Jartti L, 13-month-old children in a prospective betologia 2005;48:2460–2469 et al. Carotid artery intima-media thick- randomized trial of a low-saturated fat,362. Biessels GJ, Staekenborg S, Brunner E, ness in children with type 1 diabetes. low-cholesterol diet: the STRIP baby Brayne C, Scheltens P. Risk of dementia Diabetes 2002;51:493–498 project. Special Turku coronary Risk in diabetes mellitus: a systematic review. 375. Haller MJ, Samyn M, Nichols WW, et al. factor Intervention Project for children. Lancet Neurol 2006;5:64–74 Radial artery tonometry demonstrates Acta Paediatr 1999;88:505–512363. Ohara T, Doi Y, Ninomiya T, et al. Glu- arterial stiffness in children with type 1 380. The Dietary Intervention Study in Chil- cose tolerance status and risk of de- diabetes. Diabetes Care 2004;27:2911– dren (DISC). The Writing Group for the mentia in the community: the Hisayama 2917 DISC Collaborative Research Group. study. Neurology 2011;77:1126–1134 376. Orchard TJ, Forrest KY, Kuller LH, Efficacy and safety of lowering dietary364. Launer LJ, Miller ME, Williamson JD, Becker DJ; Pittsburgh Epidemiology of intake of fat and cholesterol in children Lazar RM, Gerstein HC, Murray AM, Diabetes Complications Study. Lipid with elevated low-density lipoprotein Sullivan M, Horowitz KR, Ding J, and blood pressure treatment goals for cholesterol. JAMA 1995;273:1429– Marcovina S, Lovato LC, Lovato J, type 1 diabetes: 10-year incidence data 1435 Margolis KL, O’Connor P, Lipkin EW, from the Pittsburgh Epidemiology of 381. McCrindle BW, Ose L, Marais AD. Effi- Hirsch J, Coker L, Maldjian J, Sunshine Diabetes Complications Study. Diabetes cacy and safety of atorvastatin in chil- JL, Truwit C, Davatzikos C, Bryan RN: Care 2001;24:1053–1059 dren and adolescents with familial Effects of intensive glucose lowering on 377. Kavey RE, Allada V, Daniels SR, et al.; hypercholesterolemia or severe hyper- brain structure and function in people American Heart Association Expert lipidemia: a multicenter, randomized, with type 2 diabetes (ACCORD MIND): Panel on Population and Prevention placebo-controlled trial. J Pediatr 2003; a randomised open-label substudy. Science; American Heart Association 143:74–80 Lancet Neurol 2011;10:969–977 Council on Cardiovascular Disease in the 382. de Jongh S, Lilien MR, op’t Roodt J,365. Silverstein J, Klingensmith G, Copeland Young; American Heart Association Stroes ES, Bakker HD, Kastelein JJ; de JS. KC, et al.; American Diabetes Associa- Council on Epidemiology and Pre- Early statin therapy restores endothelial tion. Care of children and adolescents vention; American Heart Association function in children with familial hy- with type 1 diabetes: a statement of the Council on Nutrition, Physical Activity percholesterolemia. J Am Coll Cardiol American Diabetes Association. Diabetes and Metabolism; American Heart Asso- 2002;40:2117–2121 Care 2005;28:186–212 ciation Council on High Blood Pressure 383. Wiegman A, Hutten BA, de Groot E, et al.366. Northam EA, Anderson PJ, Werther GA, Research; American Heart Association Efficacy and safety of statin therapy in Warne GL, Adler RG, Andrewes D. Council on Cardiovascular Nursing; children with familial hypercholesterol- Neuropsychological complications of American Heart Association Council emia: a randomized controlled trial. IDDM in children 2 years after disease on the Kidney in Heart Disease; Inter- JAMA 2004;292:331–337 onset. Diabetes Care 1998;21:379–384 disciplinary Working Group on Quality 384. Cho YH, Craig ME, Hing S, Gallego PH,367. Rovet J, Alvarez M. Attentional func- of Care and Outcomes Research. Car- Poon M, Chan A, Donaghue KC: Mi- tioning in children and adolescents with diovascular risk reduction in high-risk crovascular complications assessment in IDDM. Diabetes Care 1997;20:803–810 pediatric patients: a scientific statement adolescents with 2- to 5-yr duration of368. Bjørgaas M, Gimse R, Vik T, Sand T. from the American Heart Association type 1 diabetes from 1990 to 2006. Pe- Cognitive function in type 1 diabetic Expert Panel on Population and Prevention diatr Diabetes. 24 March 2011 [Epub children with and without episodes of Science; the Councils on Cardiovascular ahead of print] severe hypoglycaemia. Acta Paediatr Disease in the Young, Epidemiology and 385. Holmes GK. Screening for coeliac dis- 1997;86:148–153 Prevention, Nutrition, Physical Activity ease in type 1 diabetes. Arch Dis Child369. Nimri R, Weintrob N, Benzaquen H, and Metabolism, High Blood Pressure 2002;87:495–498 Ofan R, Fayman G, Phillip M. Insulin Research, Cardiovascular Nursing, and 386. Rewers M, Liu E, Simmons J, Redondo pump therapy in youth with type 1 di- the Kidney in Heart Disease; and the MJ, Hoffenberg EJ: Celiac disease asso- abetes: a retrospective paired study. Pe- Interdisciplinary Working Group on ciated with type 1 diabetes mellitus. diatrics 2006;117:2126–2131 Quality of Care and Outcomes Research: Endocrinol Metab Clin North Am 2004;370. Doyle EA, Weinzimer SA, Steffen AT, endorsed by the American Academy of 33:197–214 Ahern JA, Vincent M, Tamborlane WV. Pediatrics. Circulation 2006;114:2710– 387. Kurppa K, Ashorn M, Iltanen S, Koskinen A randomized, prospective trial com- 2738 LL, Saavalainen P, Koskinen O, Maki M, paring the efficacy of continuous sub- 378. McCrindle BW, Urbina EM, Dennison Kaukinen K: Celiac disease without villous cutaneous insulin infusion with multiple BA, et al.; American Heart Association atrophy in children: a prospective study. daily injections using insulin glargine. Atherosclerosis, Hypertension, and J Pediatr 2010157:373–380 Diabetes Care 2004;27:1554–1558 Obesity in Youth Committee; American 388. Abid N, McGlone O, Cardwell C,371. Perantie DC, Wu J, Koller JM, et al. Re- Heart Association Council of Cardio- McCallion W, Carson D. Clinical and gional brain volume differences associated vascular Disease in the Young; American metabolic effects of gluten free diet in with hyperglycemia and severe hypogly- Heart Association Council on Cardio- children with type 1 diabetes and coeliac cemia in youth with type 1 diabetes. Di- vascular Nursing. Drug therapy of high- disease. Pediatr Diabetes 2011;12:322–325 abetes Care 2007;30:2331–2337 risk lipid abnormalities in children 389. Roldán MB, Alonso M, Barrio R. Thyroid372. Mäkimattila S, Malmberg-Cèder K, and adolescents: a scientific statement autoimmunity in children and adoles- Häkkinen AM, et al. Brain metabolic al- from the American Heart Associa- cents with Type 1 diabetes mellitus. 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  • 51. Position Statement390. Triolo TM, Armstrong TK, McFann K, 404. Brown AF, Mangione CM, Saliba D, (SepNet). Intensive insulin therapy and et al. Additional autoimmune disease Sarkisian CA; California Healthcare pentastarch resuscitation in severe sep- found in 33% of patients at type 1 di- Foundation/American Geriatrics Society sis. N Engl J Med 2008;358:125–139 abetes onset. Diabetes Care 2011;34: Panel on Improving Care for Elders with 415. Finfer S, Chittock DR, Su SY, et al.; NICE- 1211–1213 Diabetes. Guidelines for improving the SUGAR Study Investigators. Intensive391. Kordonouri O, Deiss D, Danne T, Dorow care of the older person with diabetes versus conventional glucose control in A, Bassir C, Grüters-Kieslich A. Pre- mellitus. J Am Geriatr Soc 2003;51 critically ill patients. N Engl J Med 2009; dictivity of thyroid autoantibodies for (Suppl Guidelines):S265–S280 360:1283–1297 the development of thyroid disorders in 405. Curb JD, Pressel SL, Cutler JA, et al.; 416. 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Intensive insulin therapy and Wilcox WD, Walravens PA. Thyroid pertension in patients 80 years of age or mortality among critically ill patients: hormone replacement and growth of older. N Engl J Med 2008;358:1887–1898 a meta-analysis including NICE-SUGAR children with subclinical hypothyroid- 407. Moran A, Dunitz J, Nathan B, Saeed A, study data. CMAJ 2009;180:821–827 ism and diabetes. Diabet Med 1990;7: Holme B, Thomas W. Cystic fibrosis- 419. Saudek CD, Herman WH, Sacks DB, 299–303 related diabetes: current trends in preva- Bergenstal RM, Edelman D, Davidson394. American Diabetes Association. Diabetes lence, incidence, and mortality. Diabetes MB. A new look at screening and di- care in the school and day care setting. Care 2009;32:1626–1631 agnosing diabetes mellitus. J Clin En- Diabetes Care 2010;33(Suppl 1):S70–S74 408. Moran A, Brunzell C, Cohen RC, et al.; docrinol Metab 2008;93:2447–2453395. Arnett JJ. Emerging adulthood. A theory CFRD Guidelines Committee. Clinical 420. 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American Diabetes Association. Transi- Diabetes in Hospitals Writing Commit- 422. Czosnowski QA, Swanson JM, Lobo BL, tion in care from youth to adulthood. tee. Management of diabetes and hy- Broyles JE, Deaton PR, Finch CK. Eval- Diabetes Care. 2011;34:2477–2485 perglycemia in hospitals. Diabetes Care uation of glycemic control following398. Bryden KS, Peveler RC, Stein A, Neil A, 2004;27:553–591 discontinuation of an intensive insulin Mayou RA, Dunger DB. Clinical and 410. Moghissi ES, Korytkowski MT, DiNardo protocol. J Hosp Med 2009;4:28–34 psychological course of diabetes from M, et al.; American Association of Clinical 423. Shomali MI, Herr DL, Hill PC, adolescence to young adulthood: a lon- Endocrinologists; American Diabetes Pehlivanova M, Sharretts JM, Magee MF. gitudinal cohort study. Diabetes Care Association. American Association of Transition to target: a prospective ran- 2001;24:1536–1540 Clinical Endocrinologists and American domized trial comparing three formulae399. 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Schnipper JL, Liang CL, Ndumele CD, posure to ACE inhibitors. N Engl J Med Benefits and risks of tight glucose control Pendergrass ML. Effects of a computerized 2006;354:2443–2451 in critically ill adults: a meta-analysis. order set on the inpatient management403. American Diabetes Association. Pre- JAMA 2008;300:933–944 of hyperglycemia: a cluster-randomized conception care of women with diabetes. 414. Brunkhorst FM, Engel C, Bloos F, et al.; controlled trial. Endocr Pract 2010;16: Diabetes Care 2004;27(Suppl 1):S76–S78 German Competence Network Sepsis 209–218care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S61
  • 52. Position Statement427. Wexler DJ, Shrader P, Burns SM, to home. Cochrane Database Syst Rev with diabetic patients who have low Cagliero E. Effectiveness of a computer- 2010 (1):CD000313 health literacy. Arch Intern Med 2003; ized insulin order template in general 440. American Diabetes Association. Diabetes 163:83–90 medical inpatients with type 2 diabetes: and employment. Diabetes Care 2011; 455. Rosal MC, Ockene IS, Restrepo A, et al. a cluster randomized trial. Diabetes Care 34(Suppl 1):S82–S86 Randomized trial of a literacy-sensitive, 2010;33:2181–2183 441. American Diabetes Association: Diabetes culturally tailored diabetes self-management428. Furnary AP, Braithwaite SS. Effects of and driving. Diabetes Care 2012;35 intervention for low-income latinos: latinos outcome on in-hospital transition from (Suppl 1):S81–S86 en control. Diabetes Care 2011;34:838– intravenous insulin infusion to sub- 442. American Diabetes Association. Diabetes 844 cutaneous therapy. Am J Cardiol 2006; management in correctional institutions. 456. Osborn CY, Cavanaugh K, Wallston KA, 98:557–564 Diabetes Care 2011;34(Suppl 1):S75– et al. Health literacy explains racial dis-429. Schafer RG, Bohannon B, Franz MJ, et al.; S81 parities in diabetes medication adher- American Diabetes Association. Diabetes 443. Hoerger TJ, Segel JE, Gregg EW, ence. J Health Commun 2011;16(Suppl nutrition recommendations for health Saaddine JB. Is glycemic control im- 3):268–278 care institutions. Diabetes Care 2004;27 proving in U.S. adults? Diabetes Care 457. O’Connor PJ, Sperl-Hillen JM, Rush WA, (Suppl 1):S55–S57 2008;31:81–86 et al. Impact of electronic health record430. Curll M, Dinardo M, Noschese M, 444. Cheung BM, Ong KL, Cherny SS, Sham clinical decision support on diabetes Korytkowski MT. Menu selection, gly- PC, Tso AW, Lam KS. Diabetes preva- care: a randomized trial. Ann Fam Med caemic control and satisfaction with stan- lence and therapeutic target achievement 2011;9:12–21 dard and patient-controlled consistent in the United States, 1999 to 2006. Am J 458. Garg AX, Adhikari NK, McDonald H, carbohydrate meal plans in hospitalised Med 2009;122:443–453 et al. Effects of computerized clinical patients with diabetes. Qual Saf Health 445. Wang J, Geiss LS, Cheng YJ, et al. Long- decision support systems on practitioner Care 2010;19:355–359 term and recent progress in blood pressure performance and patient outcomes:431. Schafer RG, Bohannon B, Franz MJ, et al.; levels among U.S. adults with diagnosed a systematic review. JAMA 2005;293: American Diabetes Association. Diabetes diabetes, 1988-2008. Diabetes Care 2011; 1223–1238 nutrition recommendations for health 34:1579–1581 459. Smith SA, Shah ND, Bryant SC, et al.; care institutions. Diabetes Care 2004;27 446. Kerr EA, Heisler M, Krein SL, et al. Be- Evidens Research Group. Chronic care (Suppl 1):S55–S57 yond comorbidity counts: how do co- model and shared care in diabetes: ran-432. Boucher JL, Swift CS, Franz MJ, et al. morbidity type and severity influence domized trial of an electronic decision Inpatient management of diabetes and diabetes patients’ treatment priorities support system. Mayo Clin Proc 2008; hyperglycemia: implications for nutri- and self-management? J Gen Intern Med 83:747–757 tion practice and the food and nutrition 2007;22:1635–1640 460. McLean DL, McAlister FA, Johnson JA, professional. J Am Diet Assoc 2007;107: 447. Fernandez A, Schillinger D, Warton EM, et al.; SCRIP-HTN Investigators. A ran- 105–111 et al. Language barriers, physician- domized trial of the effect of community433. Korytkowski MT, Salata RJ, Koerbel GL, patient language concordance, and gly- pharmacist and nurse care on improving et al. Insulin therapy and glycemic con- cemic control among insured Latinos blood pressure management in patients trol in hospitalized patients with di- with diabetes: the Diabetes Study of with diabetes mellitus: study of cardio- abetes during enteral nutrition therapy: Northern California (DISTANCE). J Gen vascular risk intervention by pharma- a randomized controlled clinical trial. Intern Med 2011;26:170–176 cists-hypertension (SCRIP-HTN). Arch Diabetes Care 2009;32:594–596 448. The Chronic Care Model: Improving Intern Med 2008;168:2355–2361434. Umpierrez GE. Basal versus sliding-scale Chronic Illness Care. 2011. 461. Wubben DP, Vivian EM. Effects of phar- regular insulin in hospitalized patients 449. Coleman K, Austin BT, Brach C, Wagner macist outpatient interventions on adults with hyperglycemia during enteral nu- EH. Evidence on the Chronic Care with diabetes mellitus: a systematic re- trition therapy. Diabetes Care 2009;32: Model in the new millennium. Health Aff view. Pharmacotherapy 2008;28:421–436 751–753 (Millwood) 2009;28:75–85 462. Davidson MB, Ansari A, Karlan VJ. Effect435. Klonoff DC, Perz JF. Assisted monitoring 450. Parchman ML, Zeber JE, Romero RR, of a nurse-directed diabetes disease of blood glucose: special safety needs Pugh JA. Risk of coronary artery disease management program on urgent care/ for a new paradigm in testing glucose. in type 2 diabetes and the delivery of emergency room visits and hospital- J Diabetes Sci Tech 2010;4:1027–1031 care consistent with the chronic care izations in a minority population. Di-436. D’Orazio P, Burnett RW, Fogh-Andersen model in primary care settings: a STAR- abetes Care 2007;30:224–227 N, et al.; International Federation of Net study. Med Care 2007;45:1129– 463. Stone RA, Rao RH, Sevick MA, et al. Clinical Chemistry Scientific Division 1134 Active care management supported by Working Group on Selective Electrodes 451. Katon WJ, Lin EH, Von Korff M, et al. home telemonitoring in veterans with and Point of Care Testing. Approved Collaborative care for patients with de- type 2 diabetes: the DiaTel randomized IFCC recommendation on reporting re- pression and chronic illnesses. N Engl J controlled trial. Diabetes Care 2010;33: sults for blood glucose (abbreviated). Med 2010;363:2611–2620 478–484 Clin Chem 2005;51:1573–1576 452. Davidson MB. How our current medical 464. Berikai P, Meyer PM, Kazlauskaite R, Savoy437. Dungan K, Chapman J, Braithwaite SS, care system fails people with diabetes: B, Kozik K, Fogelfeld L. Gain in patients’ Buse J. Glucose measurement: con- lack of timely, appropriate clinical deci- knowledge of diabetes management tar- founding issues in setting targets for in- sions. Diabetes Care 2009;32:370–372 gets is associated with better glycemic con- patient management. Diabetes Care 453. Grant RW, Pabon-Nau L, Ross KM, trol. Diabetes Care 2007;30:1587–1589 2007;30:403–409 Youatt EJ, Pandiscio JC, Park ER. Di- 465. Shojania KG, Ranji SR, McDonald KM,438. Boyd JC, Bruns DE. Quality specif- abetes oral medication initiation and et al. Effects of quality improvement ications for glucose meters: assessment intensification: patient views compared strategies for type 2 diabetes on glycemic by simulation modeling of errors in in- with current treatment guidelines. Di- control: a meta-regression analysis. sulin dose. Clin Chem 2001;47:209–214 abetes Educ 2011;37:78–84 JAMA 2006;296:427–440439. Shepperd S, McClaran J, Phillips CO, 454. Schillinger D, Piette J, Grumbach K, et al. 466. O’Connor PJ, Bodkin NL, Fradkin J, et al. Discharge planning from hospital Closing the loop: physician communication et al. Diabetes performance measures:S62 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 care.diabetesjournals.org
  • 53. Position Statement current status and future directions. 470. Cebul RD, Love TE, Jain AK, Hebert CJ. 474. Pullen-Smith B, Carter-Edwards L, Leathers Diabetes Care 2011;34:1651–1659 Electronic health records and quality of KH. Community health ambassadors:467. Peikes D, Chen A, Schore J, Brown R. diabetes care. N Engl J Med 2011;365: a model for engaging community leaders Effects of care coordination on hospi- 825–833 to promote better health in North Caro- talization, quality of care, and health care 471. Ralston JD, Hirsch IB, Hoath J, Mullen lina. J Public Health Manag Pract 2008; expenditures among Medicare benefi- M, Cheadle A, Goldberg HI. Web-based 14(Suppl):S73–S81 ciaries: 15 randomized trials. JAMA collaborative care for type 2 diabetes: 475. Bojadzievski T, Gabbay RA. Patient- 2009;301:603–618 a pilot randomized trial. Diabetes Care centered medical home and diabetes.468. Feifer C, Nemeth L, Nietert PJ, et al. 2009;32:234–239 Diabetes Care 2011;34:1047–1053 Different paths to high-quality care: 472. Battersby M, Von Korff M, Schaefer J, 476. Rosenthal MB, Cutler DM, Feder J. three archetypes of top-performing et al. Twelve evidence-based principles The ACO rulesdstriking the balance practice sites. Ann Fam Med 2007;5: for implementing self-management support between participation and transfor- 233–241 in primary care. Jt Comm J Qual Patient Saf mative potential. N Engl J Med 2011;469. Ornstein S, Nietert PJ, Jenkins RG, et al. 2010;36:561–570 365:e6 Improving diabetes care through a 473. Grant RW, Wald JS, Schnipper JL, et al. 477. Washington AE, Lipstein SH: The Pa- multicomponent quality improvement Practice-linked online personal health tient-Centered Outcomes Research In- model in a practice-based research records for type 2 diabetes mellitus: stitute: Promoting better information, network. Am J Med Qual 2007;22: a randomized controlled trial. Arch In- decisions, and health. N Engl J Med 34–41 tern Med 2008;168:1776–1782 2011;365:e31care.diabetesjournals.org DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 S63