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Standards of Medical Care in Diabetes—2008

Abbreviations: ABI, ankle-brachial index • ACE, angiotensin-converting enzyme • ADAG, A1C-Derived Average Glucose • ARB, angiotensin receptor blocker • CAD, coronary artery disease • CBG, capillary blood glucose • CHD, coronary heart disease • CHF, congestive heart failure • CKD, chronic kidney disease • CMS, Centers for Medicare and Medicaid Services • CSII, continuous subcutaneous insulin infusion • CVD, cardiovascular disease • DCCT, Diabetes Control and Complications Trial • DKA, diabetic ketoacidosis • DMMP, diabetes medical management plan • DPN, distal symmetric polyneuropathy • DPP, Diabetes Prevention Program • DRS, Diabetic Retinopathy Study • DSME, diabetes self-management education • DSMT, diabetes self-management training • eAG, estimated average glucose • ECG, electrocardiogram • EDIC, Epidemiology of Diabetes Interventions and Complications • ERP, education recognition program • ESRD, end-stage renal disease • ETDRS, Early Treatment Diabetic Retinopathy Study • FDA, Food and Drug Administration • FPG, fasting plasma glucose • GDM, gestational diabetes mellitus • GFR, glomerular filtration rate • ICU, intensive care unit • IFG, impaired fasting glucose • IGT, impaired glucose tolerance • MICU, medical ICU • MNT, medical nutrition therapy • NDEP, National Diabetes Education Program • NPDR, nonproliferative diabetic retinopathy • OGTT, oral glucose tolerance test • PAD, peripheral arterial disease • PDR, proliferative diabetic retinopathy • PPG, postprandial plasma glucose • RAS, renin-angiotensin system • RDA, recommended dietary allowance • SICU, surgical ICU • SMBG, self-monitoring of blood glucose • TSH, thyroid-stimulating hormone • TZD, thiazolidinedione • UKPDS, U.K. Prospective Diabetes Study

	INTRODUCTION

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

 
Diabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes.

These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to refs. 1–3.

The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

	I. CLASSIFICATION AND DIAGNOSIS

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

• Type 1 diabetes (results from β-cell destruction, usually leading to absolute insulin deficiency)
  
• Type 2 diabetes (results from a progressive insulin secretory defect on the background of insulin resistance)
  
• Other specific types of diabetes due to other causes, e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of AIDS or after organ transplantation)
  
• Gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy)
  

B. Diagnosis of diabetes

Recommendations

• The fasting plasma glucose (FPG) test is the preferred test to diagnose diabetes in children and nonpregnant adults. (E)
  
• Use of the A1C for the diagnosis of diabetes is not recommended at this time. (E)
  

Due to lack of evidence on prognostic significance and diagnostic thresholds, the use of the A1C for the diagnosis of diabetes is not recommended at this time.

C. Diagnosis of pre-diabetes
Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is categorized as either IFG or impaired glucose tolerance (IGT), depending on whether it is identified through the FPG or the OGTT:

• IFG = FPG 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l)
  
• IGT = 2-h plasma glucose 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l)
  

	II. TESTING FOR PRE-DIABETES AND DIABETES IN ASYMPTOMATIC PATIENTS

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

 
Recommendations

• Testing to detect pre-diabetes and type 2 diabetes in asymptomatic people should be considered in adults who are overweight or obese (BMI 25 kg/m²) and who have one or more additional risk factors for diabetes (Table 3). In those without these risk factors, testing should begin at age 45. (B)
  
• If tests are normal, repeat testing should be carried out at least at 3-year intervals. (E)
  
• To test for pre-diabetes or diabetes, either an FPG test or a 2-h OGTT (75-g glucose load) or both are appropriate. (B)
  
• An OGTT may be considered in patients with IFG to better define the risk of diabetes. (E)
  
• In those identified with pre-diabetes, identify and, if appropriate, treat other CVD risk factors. (B)
  

Recommendations for testing for pre-diabetes and diabetes in asymptomatic, undiagnosed adults are listed in Table 3. Testing should be considered in all adults with BMI 25 kg/m² and one or more risk factors for diabetes. Because age is a major risk factor for diabetes, testing of those without other risk factors should begin no later than age 45.

Either FPG testing or the 2-h OGTT is appropriate for testing. The 2-h OGTT identifies people with either IFG or IGT and, thus, more prediabetic people at increased risk for the development of diabetes and CVD. It should be noted that the two tests do not necessarily detect the same prediabetic individuals (9). The efficacy of interventions for primary prevention of type 2 diabetes (10–16) has primarily been demonstrated among individuals with IGT, not among individuals with IFG (who do not also have IGT). As noted in the diagnosis section (I.B), the FPG test is more convenient, more reproducible, less costly, and easier to administer than the 2-h OGTT (4,5). An OGTT may be useful in patients with IFG to better define the risk of diabetes.

The appropriate interval between tests is not known (17). The rationale for the 3-year interval is that false negatives will be repeated before substantial time elapses, and there is little likelihood that an individual will develop significant complications of diabetes within 3 years of a negative test result.

Because of the need for follow-up and discussion of abnormal results, testing should be carried out within the health care setting. Community screening outside a health care setting is not recommended because people with positive tests may not seek appropriate follow-up testing and care, and, conversely, there may be failure to ensure appropriate repeat testing for individuals who test negative. Community screening may also be poorly targeted, i.e., it may fail to reach the groups most at risk and inappropriately test those at low risk (the worried well) or even those already diagnosed (18,19).

B. Testing for type 2 diabetes in children
The incidence of type 2 diabetes in adolescents has increased dramatically in the last decade, especially in minority populations (20), although the disease remains rare in the general population (21). Consistent with recommendations for adults, children and youth at increased risk for the presence or the development of type 2 diabetes should be tested (22). The recommendations of the ADA consensus statement on type 2 diabetes in children and youth are summarized in Table 4.

	III. DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS (GDM)

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

 
Recommendations

• Screen for GDM using risk factor analysis and, if appropriate, use of an OGTT. (C)
  
• Women with GDM should be screened for diabetes 6–12 weeks postpartum and should be followed up with subsequent screening for the development of diabetes or pre-diabetes. (E)
  

Because of the risks of GDM to the mother and neonate, screening and diagnosis are warranted. The screening and diagnostic strategies, based on the 2004 ADA position statement on gestational diabetes mellitus (23), are outlined in Table 5.

Because women with a history of GDM have a greatly increased subsequent risk for diabetes (24), they should be screened for diabetes 6–12 weeks postpartum, using standard criteria, and should be followed up with subsequent screening for the development of diabetes or pre-diabetes, as outlined in Section II. For information on the National Diabetes Education Program (NDEP) campaign to prevent type 2 diabetes in women with GDM, go to www.ndep.nih.gov/diabetes/pubs/NeverTooEarly_Tipsheet.pdf.

	IV. PREVENTION/DELAY OF TYPE 2 DIABETES

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

 
Recommendations

• Patients with IGT (A) or IFG (E) should be given counseling on weight loss of 5–10% of body weight, as well as on increasing physical activity to at least 150 min/week of moderate activity such as walking.
  
• Follow-up counseling appears to be important for success. (B)
  
• Based on potential cost savings of diabetes prevention, such counseling should be covered by third-party payors. (E)
  
• In addition to lifestyle counseling, metformin may be considered in those who are at very high risk (combined IFG and IGT plus other risk factors) and who are obese and under 60 years of age. (E)
  
• Monitoring for the development of diabetes in those with pre-diabetes should be performed every year. (E)
  

	V. DIABETES CARE

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

 
A. Initial evaluation
A complete medical evaluation should be performed to classify the diabetes, detect the presence of diabetes complications, review previous treatment and glycemic control in patients with established diabetes, assist in formulating a management plan, and provide a basis for continuing care. Laboratory tests appropriate to the evaluation of each patient's medical condition should be performed. A focus on the components of comprehensive care (Table 7) will assist the health care team to ensure optimal management of the patient with diabetes.

The management plan should be formulated as an individualized therapeutic alliance among the patient and family, the physician, and other members of the health care team. A variety of strategies and techniques should be used to provide adequate education and development of problem-solving skills in the various aspects of diabetes management. Implementation of the management plan requires that each aspect is understood and agreed on by the patient and the care providers and that the goals and treatment plan are reasonable. Any plan should recognize diabetes self-management education (DSME) as an integral component of care. In developing the plan, consideration should be given to the patient's age, school or work schedule and conditions, physical activity, eating patterns, social situation and personality, cultural factors, and presence of complications of diabetes or other medical conditions.

C. Glycemic control
1. Assessment of glycemic control.
Two primary techniques are available for health providers and patients to assess the effectiveness of the management plan on glycemic control: patient self-monitoring of blood glucose (SMBG) and A1C measurement. In addition, in recent years technologies for continuous monitoring of interstitial glucose have entered the market.

a. Self-monitoring of blood glucose

Recommendations

• SMBG should be carried out three or more times daily for patients using multiple insulin injections or insulin pump therapy. (A)
  
• For patients using less frequent insulin injections, noninsulin therapies, or medical nutrition therapy (MNT) alone, SMBG may be useful in achieving glycemic goals. (E)
  
• To achieve postprandial glucose targets, postprandial SMBG may be appropriate. (E)
  
• When prescribing SMBG, ensure that patients receive initial instruction in, and routine follow-up evaluation of, SMBG technique and their ability to use data to adjust therapy. (E)
  
• Continuous glucose monitoring may be a supplemental tool to SMBG for selected patients with type 1 diabetes, especially those with hypoglycemia unawareness. (E)
  

The frequency and timing of SMBG should be dictated by the particular needs and goals of the patients. SMBG is especially important for patients treated with insulin to monitor for and prevent asymptomatic hypoglycemia and hyperglycemia. For most patients with type 1 diabetes and pregnant women taking insulin, SMBG is recommended three or more times daily. For this population, it is often difficult to reach A1C targets safely without hypoglycemia with the minimum of three daily tests. The optimal frequency and timing of SMBG for patients with type 2 diabetes on noninsulin therapy is not known but should be sufficient to facilitate reaching glucose goals. A meta-analysis of SMBG in non–insulin-treated patients with type 2 diabetes concluded that some regimen of SMBG was associated with a reduction in A1C of 0.4%. However, many of the studies in this analysis also included patient education with diet and exercise counseling and, in some cases, pharmacologic intervention, making it difficult to assess the contribution of SMBG alone to improved control (28).

Because the accuracy of SMBG is instrument and user dependent (29), it is important to evaluate each patient's monitoring technique, both initially and at regular intervals thereafter. In addition, optimal use of SMBG requires proper interpretation of the data. Patients should be taught how to use the data to adjust food intake, exercise, or pharmacological therapy to achieve specific glycemic goals, and these skills should be re-evaluated periodically.

In recent years, methods to sample interstitial fluid glucose (which correlates highly with blood glucose) in a continuous and minimally invasive way have been developed. Most microdialysis systems are inserted subcutaneously, while an early system employed "reverse iontophoresis" to move glucose across the skin. The concentration of glucose is then measured by a glucose oxidase electrode detector. These systems require calibration with SMBG readings, and the latter are still recommended for making treatment decisions. Continuous glucose sensors have alarms for hypo- and hyperglycemia. Small studies in selected patient populations have shown good correlation of readings with SMBG and decreases in the mean time spent in hypo- and hyperglycemic ranges compared with blinded sensor use (30). Although continuous glucose sensors would seem to show great promise in diabetes management, as yet no rigorous controlled trials have demonstrated improvements in long-term glycemia.

b. A1C

Recommendations

• Perform the A1C test at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control). (E)
  
• Perform the A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals. (E)
  
• Use of point-of-care testing for A1C allows for timely decisions on therapy changes, when needed. (E)
  

Table 9 contains the correlation between A1C levels and mean plasma glucose levels based on data from the Diabetes Control and Complications Trial (DCCT) (34). The correlation is based on relatively sparse data from a primarily Caucasian type 1 diabetic population. Preliminary results of the multicenter A1C-Derived Average Glucose (ADAG) Trial, presented at the European Association for the Study of Diabetes meeting in September 2007, confirmed a close correlation of A1C with mean glucose in patients with type 1, type 2, or no diabetes. Final results of this study, not available at the time this statement was completed, should allow more accurate reporting of the estimated average glucose (eAG) and improve patients’ understanding of this measure of glycemia. An updated version of Table 9, based on final results of the ADAG Trial, will be available at www.diabetes.org after publication of the study's findings in 2008.

Recommendations

• Lowering A1C to an average of 7% has clearly been shown to reduce microvascular and neuropathic complications of diabetes and, possibly, macrovascular disease. Therefore, the A1C goal for nonpregnant adults in general is <7%. (A)
  
• Epidemiologic studies have suggested an incremental (albeit, in absolute terms, a small) benefit to lowering A1C from 7% into the normal range. Therefore, the A1C goal for selected individual patients is as close to normal (<6%) as possible without significant hypoglycemia. (B)
  
• Less stringent A1C goals may be appropriate for patients with a history of severe hypoglycemia, patients with limited life expectancies, children, individuals with comorbid conditions, and those with longstanding diabetes and minimal or stable microvascular complications. (E)
  

In type 2 diabetes, the Kumamoto study (39) and the UK Prospective Diabetes Study (UKPDS) (40,41) demonstrated significant reductions in microvascular and neuropathic complications with intensive therapy. The potential of intensive glycemic control to reduce CVD in type 2 diabetes is supported by epidemiological studies (31,40–42) and a meta-analysis (43), but has not yet been demonstrated in a randomized clinical trial. Several large trials are currently under way to address this issue.

In each of these large randomized prospective clinical trials, treatment regimens that reduced average A1C to 7% (1% above the upper limits of normal) were associated with fewer long-term microvascular complications; however, intensive control was found to increase the risk of severe hypoglycemia, most notably in the DCCT, and to lead to weight gain (31,44).

Epidemiological analyses of the DCCT and UKPDS (31,35) demonstrate a curvilinear relationship between A1C and microvascular complications. Such analyses suggest that, on a population level, the greatest number of complications will be averted by taking patients from very poor control to fair or good control. These analyses also suggest that further lowering of A1C from 7 to 6% is associated with further reduction in the risk of complications, albeit the absolute risk reductions become much smaller. Given the substantially increased risk of hypoglycemia (particularly in those with type 1 diabetes) and the relatively much greater effort required to achieve near-normoglycemia, the risks of lower targets may outweigh the potential benefits on a population level. However, selected individual patients, especially those with little comorbidity and long life expectancy (who may reap the benefits of further lowering of glycemia below 7%) may, at patient and provider judgment, have glycemic targets as close to normal as possible without significant hypoglycemia becoming a barrier.

Recommended glycemic goals for nonpregnant individuals are shown in Table 8. The recommendations are based on data for A1C. The listed blood glucose goals are levels that appear to correlate with achievement of an A1C of <7%. Less stringent treatment goals may be appropriate for patients with limited life expectancies, in children, and in individuals with comorbid conditions. Severe or frequent hypoglycemia is an indication for the modification of treatment regimens, including setting higher glycemic goals.

Neither the DCCT nor the UKPDS addressed patient populations with long durations of diabetes. Clinical experience suggests that it is uncommon for significant microvascular disease to begin after 20–30 years of diabetes. Furthermore, hypoglycemia unawareness becomes more prevalent with long duration of diabetes. Therefore, in patients with longstanding diabetes (three or more decades) and minimal or stable microvascular complications, the risk-to-benefit ratio for stringent A1C goals appears high.

The issue of pre- versus postprandial SMBG targets is complex (45). Elevated postchallenge (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of FPG in some epidemiological studies. In diabetic subjects, some surrogate measures of vascular pathology, such as endothelial dysfunction, are negatively affected by postprandial hyperglycemia (46). It is clear that postprandial hyperglycemia, like preprandial hyperglycemia, contributes to elevated A1C levels, with its relative contribution being higher at A1C levels that are closer to 7%. However, outcome studies have clearly shown A1C to be the primary predictor of complications, and the glycemic control trials such as the DCCT relied overwhelmingly on preprandial SMBG. Thus, a reasonable recommendation is: In individuals who have premeal glucose values within target but have A1C values above target, monitoring postprandial plasma glucose (PPG) 1–2 h after the start of the meal and treatment aimed at reducing PPG values to <180 mg/dl will likely lower A1C and may improve outcomes.

In regard to glycemic control for women with GDM, recommendations from the Fourth International Workshop-Conference on Gestational Diabetes Mellitus (47) suggested lowering maternal capillary whole-blood glucose concentrations to:

• Preprandial: 95 mg/dl (5.3 mmol/l), and either:
  • 1-h postmeal: 140 mg/dl (7.8 mmol/l) or
    
  • 2-h postmeal: 120 mg/dl (6.7 mmol/l)
    
  
  

• Preprandial: 105 mg/dl (5.8 mmol/l), and either:
  • 1-h postmeal: 155 mg/dl (8.6 mmol/l) or
    
  • 2-h postmeal: 130 mg/dl (7.2 mmol/l)
    
  
  

3. Approach to treatment
a. Therapy for type 1 diabetes.
The DCCT clearly showed that intensive insulin therapy (three or more injections per day of insulin or continuous subcutaneous insulin infusion [CSII, or insulin pump therapy]) was a key part of improved glycemia and better outcomes (35). At the time of the study, therapy was carried out with short- and intermediate-acting human insulins. Despite better microvascular outcomes, intensive insulin therapy was associated with a marked increase in severe hypoglycemia (62 episodes per 100 patient-years of therapy). Since the time of the DCCT, a number of rapid-acting and long-acting insulin analogs have been developed. These analogs were designed to be more "physiological" in their pharmacokinetics and pharmacodynamics, and are associated with less hypoglycemia with equal A1C lowering in type 1 diabetes (48,49).

Therefore, recommended therapy for type 1 diabetes consists of the following components: 1) use of multiple dose insulin injections (3–4 injections per day of basal and prandial insulin) or CSII therapy; 2) matching of prandial insulin to carbohydrate intake, premeal blood glucose, and anticipated activity; and 3) for many patients (especially if hypoglycemia is a problem), use of insulin analogs. There are excellent reviews available that guide the initiation and management of insulin therapy to achieve desired glycemic goals (3,48,50).

b. Therapy for type 2 diabetes.
ADA and the European Association for the Study of Diabetes published a consensus statement on the approach to management of hyperglycemia in individuals with type 2 diabetes (51). Highlights of this approach are 1) intervention at the time of diagnosis with metformin in combination with lifestyle changes (MNT and exercise) and 2) continuing timely augmentation of therapy with additional agents (including early initiation of insulin therapy) as a means of achieving and maintaining recommended levels of glycemic control (i.e., A1C <7% for most patients). The overall objective is to achieve and maintain glycemic levels as close to the nondiabetic range as possible and to change interventions at as rapid a pace as titration of medications allows.

The algorithm took into account the evidence for A1C-lowering of the individual interventions, their synergies, and their expense. Of note, the consensus algorithm was developed before publications that raised concerns about increased risk of myocardial infarction with use of rosiglitazone (52,53) and before addition of black box warnings about congestive heart failure (CHF) for both rosiglitazone and pioglitazone. This new information may prompt greater caution in using the thiazolidinediones. Other medications such as pramlintide, exenatide, -glucosidase inhibitors, the glinides, and dipeptidyl peptidase IV inhibitors were not included in the consensus algorithm, owing to less glucose-lowering effectiveness, limited clinical data, and/or relative expense. However, they may be appropriate choices in individual patients to achieve glycemic goals. Initiation of insulin at time of diagnosis is recommended for individuals presenting with weight loss or other severe hyperglycemic symptoms or signs. For a list of currently approved diabetes medications, see http://ndep.nih.gov/diabetes/pubs/Drug_tables_supplement.pdf.

D. Medical Nutrition Therapy (MNT)

General recommendations

• Individuals who have pre-diabetes or diabetes should receive individualized MNT as needed to achieve treatment goals, preferably provided by a registered dietitian familiar with the components of diabetes MNT. (B)
  
• MNT should be covered by insurance and other payors. (E)
  

Energy balance, overweight, and obesity

• In overweight and obese insulin-resistant individuals, modest weight loss has been shown to reduce insulin resistance. Thus, weight loss is recommended for all overweight or obese individuals who have or are at risk for diabetes. (A)
  
• For weight loss, either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year). (A)
  
• For patients on low-carbohydrate diets, monitor lipid profiles, renal function, and protein intake (in those with nephropathy), and adjust hypoglycemic therapy as needed. (E)
  
• Physical activity and behavior modification are important components of weight loss programs and are most helpful in maintenance of weight loss. (B)
  

Primary prevention of diabetes

• Among individuals at high risk for developing type 2 diabetes, structured programs that emphasize lifestyle changes that include moderate weight loss (7% body weight) and regular physical activity (150 min/week), with dietary strategies including reduced calories and reduced intake of dietary fat, can reduce the risk for developing diabetes and are therefore recommended. (A)
  
• Individuals at high risk for type 2 diabetes should be encouraged to achieve the U.S. Department of Agriculture (USDA) recommendation for dietary fiber (14 g fiber/1,000 kcal) and foods containing whole grains (one-half of grain intake). (B)
  

Dietary fat intake in diabetes management

• Saturated fat intake should be <7% of total calories. (A)
  
• Intake of trans fat should be minimized. (E)
  

Carbohydrate intake in diabetes management

• Monitoring carbohydrate intake, whether by carbohydrate counting, exchanges, or experience-based estimation, remains a key strategy in achieving glycemic control. (A)
  
• For individuals with diabetes, the use of the glycemic index and glycemic load may provide a modest additional benefit for glycemic control over that observed when total carbohydrate is considered alone. (B)
  

Other nutrition recommendations

• Sugar alcohols and nonnutritive sweeteners are safe when consumed within the acceptable daily intake levels established by the Food and Drug Administration (FDA). (A)
  
• If adults with diabetes choose to use alcohol, daily intake should be limited to a moderate amount (one drink per day or less for adult women and two drinks per day or less for adult men). (E)
  
• Routine supplementation with antioxidants, such as vitamins E and C and carotene, is not advised because of lack of evidence of efficacy and concern related to long-term safety. (A)
  
• Benefit from chromium supplementation in people with diabetes or obesity has not been conclusively demonstrated and, therefore, cannot be recommended. (E)
  

Clinical trials/outcome studies of MNT have reported decreases in A1C of 1% in type 1 diabetes and 1–2% in type 2 diabetes, depending on the duration of diabetes (55,56). Meta-analyses of studies in nondiabetic, free-living subjects report that MNT reduces LDL cholesterol by 15–25 mg/dl (57), while clinical trials support a role for lifestyle modification in treating hypertension (58).

Because of the effects of obesity on insulin resistance, weight loss is an important therapeutic objective for overweight or obese individuals with pre-diabetes or diabetes (59). Short-term studies have demonstrated that moderate weight loss (5% of body weight) in subjects with type 2 diabetes is associated with decreased insulin resistance, improved measures of glycemia and lipemia, and reduced blood pressure (60); longer-term studies (52 weeks) showed mixed effects on A1C in adults with type 2 diabetes (61–63), and results were confounded by pharmacologic weight loss therapy. Sustained weight loss is difficult for most people to accomplish. However, the multifactorial intensive lifestyle intervention employed in the DPP, which included reduced intake of fat and calories, led to weight loss averaging 7% at 6 months and maintenance of 5% weight loss at 3 years, and these outcomes were associated with a 58% reduction in the incidence of type 2 diabetes (10). The Look AHEAD (Action for Health in Diabetes) study is a large clinical trial designed to determine whether long-term weight loss will improve glycemia and prevent cardiovascular events in subjects with type 2 diabetes. One-year results of the intensive lifestyle intervention in this trial show an average 8.6% weight loss, significant reduction of A1C, and reduction in several CVD risk factors (64). When completed, the Look AHEAD study should provide insight into the effects of long-term weight loss on important clinical outcomes.

The optimal macronutrient distribution of weight loss diets has not been established. Although low-fat diets have traditionally been promoted for weight loss, several randomized controlled trials found that subjects on low-carbohydrate diets (<130 g/day of carbohydrate) lost more weight at 6 months than subjects on low-fat diets (65,66); however, at 1 year, the difference in weight loss between the low-carbohydrate and low-fat diets was not significant and weight loss was modest with both diets. Another study of overweight women randomized to one of four diets showed significantly more weight loss at 12 months with the Atkins low-carbohydrate diet than with higher-carbohydrate diets (67). Changes in serum triglyceride and HDL cholesterol were more favorable with the low-carbohydrate diets. In one study, those subjects with type 2 diabetes demonstrated a greater decrease in A1C with a low-carbohydrate diet than with a low-fat diet (66). A recent meta-analysis showed that at 6 months, low-carbohydrate diets were associated with greater improvements in triglyceride and HDL cholesterol concentrations than low-fat diets; however, LDL cholesterol was significantly higher on the low-carbohydrate diets (68).

The recommended dietary allowance (RDA) for digestible carbohydrate is 130 g/day and is based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat. Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very-low-carbohydrate diets are unclear, and such diets eliminate many foods that are important sources of energy, fiber, vitamins, and minerals and are important in dietary palatability (69).

Although numerous studies have attempted to identify the optimal mix of macronutrients for meal plans of people with diabetes, it is unlikely that one such combination of macronutrients exists. The best mix of carbohydrate, protein, and fat appears to vary depending on individual circumstances. For those individuals seeking guidance on macronutrient distribution in healthy adults, the Dietary Reference Intakes (DRIs) may be helpful (69). It must be clearly recognized that regardless of the macronutrient mix, total caloric intake must be appropriate to weight management goal. Further, individualization of the macronutrient composition will depend on the metabolic status of the patient (e.g., lipid profile, renal function).

The primary goal with respect to dietary fat in individuals with diabetes is to limit saturated fatty acids, trans fatty acids, and cholesterol intake so as to reduce risk for CVD. Saturated and trans fatty acids are the principal dietary determinants of plasma LDL cholesterol. There is a lack of evidence on the effects of specific fatty acids on people with diabetes, so the recommended goals are consistent with those for individuals with CVD (70).

The FDA has approved five nonnutritive sweeteners for use in the U.S.: acesulfame potassium, aspartame, neotame, saccharin, and sucralose. Before being allowed on the market, all underwent rigorous scrutiny and were shown to be safe when consumed by the public, including people with diabetes and women during pregnancy. Reduced-calorie sweeteners approved by the FDA include sugar alcohols (polyols) such as erythritol, isomalt, lactitol, maltitol, mannitol, sorbitol, xylitol, tagatose, and hydrogenated starch hydrolysates. The use of sugar alcohols appears to be safe; however, they may cause diarrhea, especially in children.

Reimbursement for MNT
MNT, when delivered by a registered dietitian according to nutrition practice guidelines, is reimbursed as part of the Medicare program as overseen by the Centers for Medicare and Medicaid Services (CMS) (www.cms.hhs.gov/medicalnutritiontherapy).

E. DSME

Recommendations

• People with diabetes should receive DSME according to national standards when their diabetes is diagnosed and as needed thereafter. (B)
  
• Self-management behavior change is the key outcome of DSME and should be measured and monitored as part of care. (E)
  
• DSME should address psychosocial issues, since emotional well-being is strongly associated with positive diabetes outcomes. (C)
  
• DSME should be reimbursed by third-party payors. (E)
  

Evidence for the benefits of DSME
Since the 1990s, there has been a shift from a didactic approach, with DSME focusing on providing information, to a skill-based approach that focuses on helping those with diabetes make informed self-management choices. Several studies have found that DSME is associated with improved diabetes knowledge and improved self-care behavior (72), improved clinical outcomes such as lower A1C (73,74,76,77,80), lower self-reported weight (72), and improved quality of life (75). Better outcomes were reported for DSME interventions that were longer and included follow-up support (72), that were tailored to individual needs and preferences (71), and that addressed psychosocial issues (71,72,76). Both individual and group approaches have been found effective (81,82). There is increasing evidence for the role of a community health worker in delivering diabetes education in addition to the core team (83).

The National Standards for DSME
ADA-recognized DSME programs have staff who must be certified diabetes educators or have recent experience in diabetes education and management. The curriculum of ADA-recognized DSME programs must cover all nine areas of diabetes management, with the assessed needs of the individual determining which areas are addressed. The ADA Education Recognition Program (ERP) is a mechanism to ensure that diabetes education programs meet the National Standards and provide quality diabetes care.

Reimbursement for DSME
DSME, when provided by a program that meets ADA ERP standards, is reimbursed as part of the Medicare program as overseen by the Centers for Medicare and Medicaid Services (CMS) (www.cms.hhs.gov/DiabetesSelfManagement).

F. Physical activity

Recommendations

• People with diabetes should be advised to perform at least 150 min/week of moderate-intensity aerobic physical activity (50–70% of maximum heart rate). (A)
  
• In the absence of contraindications, people with type 2 diabetes should be encouraged to perform resistance training three times per week. (A)
  

Frequency and type of exercise
A U.S. Surgeon General's report (88) recommended that most adults accumulate at least 30 min of moderate-intensity activity on most, ideally all, days of the week. The studies included in the meta-analysis of effects of exercise interventions on glycemic control (86) had a mean number of sessions per week of 3.4, with a mean of 49 min per session. The DPP lifestyle intervention, which included 150 min per week of moderate-intensity exercise, had a beneficial effect on glycemia in those with pre-diabetes. Therefore, it seems reasonable to recommend 150 min of exercise per week for people with diabetes.

Resistance exercise improves insulin sensitivity to about the same extent as aerobic exercise (89). Clinical trials have provided strong evidence for the A1C-lowering value of resistance training in older adults with type 2 diabetes (90,91), and for an additive benefit of combined aerobic and resistance exercise in adults with type 2 diabetes (92).

Evaluation of the diabetic patient before recommending an exercise program
Prior guidelines suggested that before recommending a program of physical activity, the provider should assess patients with multiple cardiovascular risk factors for coronary artery disease (CAD). As discussed more fully in Section VI.A.5, the area of screening asymptomatic diabetic patients for CAD remains unclear, and a recent ADA consensus statement on this issue concluded that routine screening is not recommended (93). Providers should use clinical judgment in this area. Certainly, high-risk patients should be encouraged to start with short periods of low-intensity exercise and increase the intensity and duration slowly.

Providers should assess patients for conditions that might contraindicate certain types of exercise or predispose to injury, such as uncontrolled hypertension, severe autonomic neuropathy, severe peripheral neuropathy or history of foot lesions, and advanced retinopathy. The patient's age and previous physical activity level should be considered.

Exercise in the presence of nonoptimal glycemic control
Hyperglycemia.
When people with type 1 diabetes are deprived of insulin for 12–48 h and are ketotic, exercise can worsen hyperglycemia and ketosis (94); therefore, vigorous activity should be avoided in the presence of ketosis. However, it is not necessary to postpone exercise based simply on hyperglycemia, provided the patient feels well and urine and/or blood ketones are negative.

Hypoglycemia.
In individuals taking insulin and/or insulin secretagogues, physical activity can cause hypoglycemia if medication dose or carbohydrate consumption is not altered. For individuals on these therapies, added carbohydrate should be ingested if pre-exercise glucose levels are <100 mg/dl (5.6 mmol/l) (95,96). Hypoglycemia is rare in diabetic individuals who are not treated with insulin or insulin secretagogues, and no preventive measures for hypoglycemia are usually advised in these cases.

Exercise in the presence of specific long-term complications of diabetes
Retinopathy.
In the presence of proliferative diabetic retinopathy (PDR) or severe non-PDR (NPDR), vigorous aerobic or resistance exercise may be contraindicated because of the risk of triggering vitreous hemorrhage or retinal detachment (97).

Peripheral neuropathy.
Decreased pain sensation in the extremities results in increased risk of skin breakdown and infection and of Charcot joint destruction. Therefore, in the presence of severe peripheral neuropathy, it may be best to encourage non–weight-bearing activities such as swimming, bicycling, or arm exercises (98,99).

Autonomic neuropathy.
Autonomic neuropathy can increase the risk of exercise-induced injury or adverse event through decreased cardiac responsiveness to exercise, postural hypotension, impaired thermoregulation, impaired night vision due to impaired papillary reaction, and unpredictable carbohydrate delivery from gastroparesis predisposing to hypoglycemia (98). Autonomic neuropathy is also strongly associated with CVD in people with diabetes (100,101). People with diabetic autonomic neuropathy should undergo cardiac investigation before beginning physical activity more intense than that to which they are accustomed.

Albuminuria and nephropathy.
Physical activity can acutely increase urinary protein excretion. However, there is no evidence that vigorous exercise increases the rate of progression of diabetic kidney disease; thus, there is likely no need for any specific exercise restrictions for people with diabetic kidney disease (102).

G. Psychosocial assessment and care

Recommendations

• Assessment of psychological and social situation should be included as an ongoing part of the medical management of diabetes. (E)
  
• Psychosocial screening and follow-up should include, but is not limited to, attitudes about the illness, expectations for medical management and outcomes, affect/mood, general and diabetes-related quality of life, resources (financial, social, and emotional), and psychiatric history. (E)
  
• Screen for psychosocial problems such as depression, anxiety, eating disorders, and cognitive impairment when adherence to the medical regimen is poor. (E)
  

Key opportunities for screening of psychosocial status occur at diagnosis, during regularly scheduled management visits, during hospitalizations, at discovery of complications, or when problems with glucose control, quality of life, or adherence are identified (110). Patients are likely to exhibit psychological vulnerability at diagnosis and when their medical status changes, i.e., the end of the honeymoon period, when the need for intensified treatment is evident, and when complications are discovered (105,107).

Issues known to impact self-management and health outcomes include but are not limited to: attitudes about the illness, expectations for medical management and outcomes, affect/mood, general and diabetes-related quality of life, resources (financial, social, and emotional) (106), and psychiatric history (107,110,111). Screening tools are available for a number of these areas (112). Indications for referral to a mental health specialist familiar with diabetes management may include gross noncompliance with medical regimen (by self or others) (111), depression with the possibility of self-harm (104,113), debilitating anxiety (alone or with depression), indications of an eating disorder (114), and cognitive functioning that significantly impairs judgment (113). It is preferable to incorporate psychological assessment and treatment into routine care rather than wait for identification of a specific problem or deterioration in psychological status (115). Although the clinician may not feel qualified to treat psychological problems, utilizing the patient-provider relationship as a foundation for further treatment can increase the likelihood that the patient will accept referral for other services. It is important to establish that emotional well-being is part of diabetes management (110).

H. When treatment goals are not met
For a variety of reasons, some people with diabetes and their health care providers do not achieve the desired goals of treatment (Table 8). Intensification of the treatment regimen is suggested and may include assessment of barriers to adherence including income; educational attainment; and competing demands, including those related to family responsibilities and family dynamics; culturally appropriate and enhanced DSME; co-management with a diabetes team; referral to a medical social worker for assistance with insurance coverage; change in pharmacological therapy; initiation of or increase in SMBG; more frequent contact with the patient; and referral to an endocrinologist.

I. Intercurrent illness
The stress of illness, trauma, and/or surgery frequently aggravates glycemic control and may precipitate diabetic ketoacidosis (DKA) or nonketotic hyperosmolar state, both of which are life-threatening conditions that require immediate medical care to prevent complications and death (116). Any condition leading to deterioration in glycemic control necessitates more frequent monitoring of blood glucose and (in ketosis-prone patients) urine or blood ketones. Marked hyperglycemia requires temporary adjustment of the treatment program and—if accompanied by ketosis, vomiting, or alteration in the level of consciousness—immediate interaction with the diabetes care team. The patient treated with noninsulin therapies or MNT alone may temporarily require insulin. Adequate fluid and caloric intake must be ensured. Infection or dehydration is more likely to necessitate hospitalization of the person with diabetes than the person without diabetes.

The hospitalized patient should be treated by a physician with expertise in the management of diabetes. For further information on management of patients with hyperglycemia in the hospital, see Section VIII.A. For further information on management of DKA or nonketotic hyperosmolar state, refer to the ADA position statement on hyperglycemic crises (116).

J. Hypoglycemia

Recommendations

• Glucose (15–20 g) is the preferred treatment for the conscious individual with hypoglycemia, although any form of carbohydrate that contains glucose may be used. If SMBG 15 min after treatment shows continued hypoglycemia, the treatment should be repeated. Once SMBG glucose returns to normal, the individual should consume a meal or snack to prevent recurrence of hypoglycemia. (E)
  
• Glucagon should be prescribed for all individuals at significant risk of severe hypoglycemia, and caregivers or family members of these individuals should be instructed in its administration. Glucagon administration is not limited to health care professionals. (E)
  
• Individuals with hypoglycemia unawareness or one or more episodes of severe hypoglycemia should be advised to raise their glycemic targets to strictly avoid further hypoglycemia for at least several weeks in order to partially reverse hypoglycemia unawareness and reduce risk of future episodes. (B)
  

Severe hypoglycemia (where the individual requires the assistance of another person and cannot be treated with oral carbohydrate due to confusion or unconsciousness) should be treated using emergency glucagon kits, which require a prescription. Those in close contact with, or having custodial care of, people with hypoglycemia-prone diabetes (family members, roommates, school personnel, child care providers, correctional institution staff, or coworkers) should be instructed in use of such kits. An individual does not need to be a health care professional to safely administer glucagon. Care should be taken to ensure that unexpired glucagon kits are available.

Prevention of hypoglycemia is a critical component of diabetes management. Teaching people with diabetes to balance insulin use, carbohydrate intake, and exercise is a necessary but not always sufficient strategy. In type 1 diabetes and severely insulin-deficient type 2 diabetes, the syndrome of hypoglycemia unawareness, or hypoglycemia-associated autonomic failure, can severely compromise stringent diabetes control and quality of life. The deficient counter-regulatory hormone release and autonomic responses in this syndrome are both risk factors for, and caused by, hypoglycemia. A corollary to this "vicious cycle" is that several weeks of avoidance of hypoglycemia has been demonstrated to improve counter-regulation and awareness to some extent in many patients (117,119,120). Hence, patients with one or more episodes of severe hypoglycemia may benefit from at least short-term relaxation of glycemic targets.

K. Immunization

Recommendations

• Annually provide an influenza vaccine to all diabetic patients 6 months of age. (C)
  
• Provide at least one lifetime pneumococcal vaccine for adults with diabetes. A one-time revaccination is recommended for individuals 65 years of age previously immunized when they were <65 years of age if the vaccine was administered >5 years ago. Other indications for repeat vaccination include nephrotic syndrome, chronic renal disease, and other immunocompromised states, such as after transplantation. (C)
  

Safe and effective vaccines are available that can greatly reduce the risk of serious complications from these diseases (122,123). In a case-control series, influenza vaccine was shown to reduce diabetes-related hospital admission by as much as 79% during flu epidemics (122). There is sufficient evidence to support that people with diabetes have appropriate serologic and clinical responses to these vaccinations. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends influenza and pneumococcal vaccines for all individuals of any age with diabetes (http://www.cdc.gov/vaccines/recs). For a complete discussion on the prevention of influenza and pneumococcal disease in people with diabetes, consult the technical review and position statement on this subject (121,124).

	VI. PREVENTION AND MANAGEMENT OF DIABETES COMPLICATIONS

TOP INTRODUCTION I. CLASSIFICATION AND DIAGNOSIS II. TESTING FOR PRE-DIABETES... III. DETECTION AND DIAGNOSIS... IV. PREVENTION/DELAY OF TYPE... V. DIABETES CARE VI. PREVENTION AND MANAGEMENT... VII. DIABETES CARE IN... VIII. DIABETES CARE IN... IX. HYPOGLYCEMIA AND... X. THIRD-PARTY REIMBURSEMENT FOR... XI. STRATEGIES FOR IMPROVING... References

 
A. CVD
CVD is the major cause of morbidity and mortality for individuals with diabetes and is the largest contributor to the direct and indirect costs of diabetes. The common conditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for CVD, and diabetes itself confers independent risk. Numerous studies have shown the efficacy of controlling cardiovascular risk factors in preventing or slowing CVD in people with diabetes. Evidence is summarized in the following sections and reviewed in detail in the ADA technical reviews on hypertension (125), dyslipidemia (126), aspirin therapy (127), and smoking cessation (128), and in the AHA/ADA scientific statement on prevention of CVD in people with diabetes (129). Emphasis should be placed on reducing cardiovascular risk factors, and clinicians should be alert for signs and symptoms of atherosclerosis.

1. Hypertension/blood pressure control

Recommendations

Screening and diagnosis

• Blood pressure should be measured at every routine diabetes visit. Patients found to