Standards of Medical Care in Diabetes

In 1997, the ADA issued new diagnostic and classification criteria (4); in 2003, modifications were made regarding the diagnosis of impaired fasting glucose (IFG) (5). The classification of diabetes includes four clinical classes:

• 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, drug or chemical induced).

• Gestational diabetes mellitus (GDM) (diagnosed during pregnancy).

Criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2. Three ways to diagnose diabetes are available, and each must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present. Although the 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than fasting plasma glucose (FPG) to diagnose diabetes, it is poorly reproducible and rarely performed in practice. Because of ease of use, acceptability to patients, and lower cost, the FPG is the preferred screening and diagnostic test. It should be noted that the vast majority of people who meet diagnostic criteria for diabetes by OGTT, but not by FPG, will have an A1C value <7.0%. The use of the A1C for the diagnosis of diabetes is not recommended at this time.

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 FPG or an 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)

Recently, IFG and IGT have been officially termed “pre-diabetes.” Both categories, IFG and IGT, are risk factors for future diabetes and cardiovascular disease (CVD). Recent studies have shown that modest weight loss and regular physical activity can reduce the rate of progression of IGT to type 2 diabetes (6–8). Drug therapy (metformin [8], acarbose [9], and orlistat [10] and troglitazone [no longer clinically available] [11]) has been shown to be effective in reducing progression to diabetes, though generally not as effectively as intensive lifestyle interventions.

Generally, people with type 1 diabetes present with acute symptoms of diabetes and markedly elevated blood glucose levels. Type 2 diabetes is frequently not diagnosed until complications appear, and approximately one-third of all people with diabetes may be undiagnosed. Although the burden and natural history of diabetes is well known and although there is good evidence for benefit from treating cases diagnosed in the context of usual clinical care, there are no randomized trials demonstrating the benefits of early diagnosis through screening of asymptomatic individuals (12). Nevertheless, there is sufficient indirect evidence to justify opportunistic screening in a clinical setting of individuals at high risk. Criteria for testing for diabetes in asymptomatic, undiagnosed adults are listed in Table 3. The recommended screening test for nonpregnant adults is the FPG. The OGTT is more sensitive for the diagnosis of diabetes and pre-diabetes, but is impractical and expensive as a screening procedure.

The incidence of type 2 diabetes in children and adolescents has increased dramatically in the last decade. Consistent with screening recommendations for adults, only children and youth at increased risk for the presence or the development of type 2 diabetes should be tested (13) (Table 4).

Risk assessment for GDM should be undertaken at the first prenatal visit. Women with clinical characteristics consistent with a high risk for GDM (those with marked obesity, personal history of GDM, glycosuria, or a strong family history of diabetes) should undergo glucose testing as soon as possible (14). An FPG ≥126 mg/dl or a casual plasma glucose ≥200 mg/dl meets the threshold for the diagnosis of diabetes and needs to be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present. High-risk women not found to have GDM at the initial screening and average-risk women should be tested between 24 and 28 weeks of gestation. Testing should follow one of two approaches:

• One-step approach: perform a diagnostic 100-g OGTT

• Two-step approach: perform an initial screening by measuring the plasma or serum glucose concentration 1 h after a 50-g oral glucose load (glucose challenge test [GCT]) and perform a diagnostic 100-g OGTT on that subset of women exceeding the glucose threshold value on the GCT. When the two-step approach is used, a glucose threshold value ≥140 mg/dl identifies ∼80% of women with GDM, and the yield is further increased to 90% by using a cutoff of ≥130 mg/dl.

• Diagnostic criteria for the 100-g OGTT are as follows: ≥95 mg/dl fasting, ≥180 mg/dl at 1 h, ≥155 mg/dl at 2 h, and ≥140 mg/dl at 3 h. Two or more of the plasma glucose values must be met or exceeded for a positive diagnosis. The test should be done in the morning after an overnight fast of 8–14 h. The diagnosis can be made using a 75-g glucose load, but that test is not as well validated for detection of at-risk infants or mothers as the 100-g OGTT.

• Low-risk status requires no glucose testing, but this category is limited to those women meeting all of the following characteristics:

  • Age <25 years.

  • Weight normal before pregnancy.

  • Member of an ethnic group with a low prevalence of GDM.

  • No known diabetes in first-degree relatives.

  • No history of abnormal glucose tolerance.

  • No history of poor obstetric outcome.

• The FPG is the preferred test to screen for and diagnose diabetes in children and nonpregnant adults. (E)

• Screen for diabetes in high-risk, asymptomatic, undiagnosed adults and children within the health care setting. (E)

• In those with pre-diabetes (IFG/IGT), lifestyle modification should bestrongly recommended and progression of glycemic abnormalities followed by screening at least yearly. (A)

• Screen for diabetes in pregnancy using risk factor analysis and screening tests as noted; the OGTT is the preferred screening test in pregnancy. (E)

A complete medical evaluation should be performed to classify the patient, detect the presence or absence of diabetes complications, assist in formulating a management plan, and provide a basis for continuing care. If the diagnosis of diabetes has already been made, the evaluation should review the previous treatment and the past and present degrees of glycemic control. Laboratory tests appropriate to the evaluation of each patient’s general medical condition should be performed. A focus on the components of comprehensive care (Table 5) will assist the health care team to ensure optimal management of the patient with diabetes.

People with diabetes should receive medical care from a physician-coordinated team. Such teams may include, but are not limited to, physicians, nurse practitioners, physician’s assistants, nurses, dietitians, pharmacists, and mental health professionals with expertise and a special interest in diabetes. It is essential in this collaborative and integrated team approach that individuals with diabetes assume an active role in their care.

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. Any plan should recognize diabetes self-management education 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 orother medical conditions. 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.

Glycemic control is fundamental to the management of diabetes. Prospective randomized clinical trials such as the Diabetes Control and Complications Trial (DCCT) (15) and the U.K. Prospective Diabetes Study (UKPDS) (16,17) have shown that improved glycemic control is associated with sustained decreased rates of retinopathy, nephropathy, and neuropathy (18). In these 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 and weight gain (19,20). Epidemiological studies support the potential of intensive glycemic control in the reduction of CVD (15–20).

Recommended glycemic goals for nonpregnant individuals are shown in Table 6. A major limitation to the available data are that they do not identify the optimum level of control for particular patients, as there are individual differences in the risks of hypoglycemia, weight gain, and other adverse effects. Furthermore, with multifactorial interventions, it is unclear how different components (e.g., educational interventions, glycemic targets, lifestyle changes, and pharmacological agents) contribute to the reduction of complications. There are no clinical trial data available for the effects of glycemic control in patients with advanced complications, the elderly (≥65 years of age), or young children (<13 years of age). Less stringent treatment goals may be appropriate for patients with limited life expectancies, in the very young or older adults, and in individuals with comorbid conditions. Severe or frequent hypoglycemia is an indication for the modification of treatment regimens, including setting higher glycemic goals.

More stringent goals (i.e., a normal A1C, <6%) can be considered in individual patients based on epidemiological analyses that suggest that there is no lower limit of A1C at which further lowering does not reduce risk of complications, at the risk of increased hypoglycemia (particularly in those with type 1 diabetes). However, the absolute risks and benefits of lower targets are unknown. The risks and benefits of an A1C goal of <6% are currently being tested in an ongoing study (ACCORD [Action to Control Cardiovascular Risk in Diabetes]) in type 2 diabetes (21). Elevated postchallenge (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of FPG in some epidemiological studies. Postprandial plasma glucose (PPG) levels >140 mg/dl are unusual in nondiabetic individuals, although large evening meals can be followed by plasma glucose values up to 180 mg/dl. There are now pharmacological agents that primarily modify PPG and thereby reduce A1C in parallel. Thus, in individuals who have premeal glucose values within target but who are not meeting A1C targets, consideration of monitoring PPG 1–2 h after the start of the meal and treatment aimed at reducing PPG values <180 mg/dl may lower A1C. However, it should be noted that the effect of these approaches on micro- or macrovascular complications has not been studied (22).

For information on glycemic control for women with GDM, refer to the ADA position statement “Gestational Diabetes Mellitus” (14). For information on glycemic control during pregnancy in women with preexisting diabetes, refer to Medical Management of Pregnancy Complicated by Diabetes (3rd ed.) (23).

For a variety of reasons, some people with diabetes and their health care providers do not achieve the desired goals of treatment (Table 6). In such instances, additional actions suggested include enhanced diabetes self-management education, comanagement with a diabetes team, change in pharmacological therapy, initiation of or increase in self-monitoring of blood glucose (SMBG), more frequent contact with the patient, and referral to an endocrinologist.

The stress of illness frequently aggravates glycemic control and necessitates more frequent monitoring of blood glucose and urine or blood ketones. A vomiting illness accompanied by ketosis may indicate diabetic ketoacidosis (DKA), a life-threatening condition that requires immediate medical care to prevent complications and death; the possibility of DKA should always be considered (24). Marked hyperglycemia requires temporary adjustment of the treatment program and, if accompanied by ketosis, frequent interaction with the diabetes care team. The patient treated with oral glucose-lowering agents or medical nutrition therapy (MNT) alone may temporarily require insulin. Adequate fluid and caloric intake must be assured. 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, and recent studies suggest that achieving very stringent glycemic control may reduce mortality in the immediate postmyocardial infarction period (25). Aggressive glycemic management with insulin may reduce morbidity in patients with severe acute illness (26).

For information on management of patients in the hospital, refer to the ADA position statement titled “Hyperglycemic Crises in Diabetes ” (24).

• Lowering A1C has been associated with a reduction of microvascular and neuropathic complications of diabetes. (A)

• Develop or adjust the management plan to achieve normal or near-normal glycemia with an A1C goal of <7%. (B)

• More stringent goals (i.e., a normal A1C, <6%) can be considered in individual patients. (B)

• Lowering A1C may lower the risk of myocardial infarction and cardiovascular death. (B)

• Aggressive glycemic management with insulin may reduce morbidity in patients with severe acute illness, perioperatively and following myocardial infarction. (B)

• Less stringent treatment goals may be appropriate for patients with a history of severe hypoglycemia, patients with limited life expectancies, very young children or older adults, and individuals with comorbid conditions. (E)

Techniques are available for health providers and patients to assess the effectiveness of the management plan on glycemic control.

The ADA’s consensus statements on SMBG provide a comprehensive review of the subject (27,28). Major clinical trials assessing the impact of glycemic control on diabetes complications have included SMBG as part of multifactorial interventions, suggesting that SMBG is a component of effective therapy. SMBG allows patients to evaluate their individual response to therapy and assess whether glycemic targets are being achieved. Results of SMBG can be useful in preventing hypoglycemia and adjusting medications, MNT, and physical activity.

The frequency and timing of SMBG should be dictated by the particular needs and goals of the patients. Daily SMBG is especially important for patients treated with insulin to monitor for and prevent asymptomatic hypoglycemia. For most patients with type 1 diabetes and pregnant women taking insulin, SMBG is recommended three or more times daily. The optimal frequency and timing of SMBG for patients with type 2 diabetes is not known but should be sufficient to facilitate reaching glucose goals. When adding to or modifying therapy, type 1 and type 2 diabetic patients should test more often than usual. The role of SMBG in stable diet-treated patients with type 2 diabetes is not known.

Because the accuracy of SMBG is instrument- and user-dependent (29), it is important for health care providers 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. Health professionals should evaluate at regular intervals the patient’s ability to use SMBG data to guide treatment.

• SMBG is an integral component of diabetes therapy. (B)

• Include SMBG in the management plan. (E)

• Instruct the patient in SMBG and routinely evaluate the patient’s technique and ability to use data to adjust therapy. (E)

By performing an A1C test, health providers can measure a patient’s average glycemia over the preceding 2–3 months (29) and, thus, assess treatment efficacy. A1C testing should be performed routinely in all patients with diabetes, first to document the degree of glycemic control at initial assessment and then as part of continuing care. Since the A1C test reflects mean glycemia over the preceding 2–3 months, measurement approximately every 3 months is required to determine whether a patient’s metabolic control has been reached and maintained within the target range. Thus, regular performance of the A1C test permits detection of departures from the target (Table 6) in a timely fashion. For any individual patient, the frequency of A1C testing should be dependent on the clinical situation, the treatment regimen used, and the judgment of the clinician.

Glycemic control is best judged by the combination of the results of the patient’s SMBG testing (as performed) and the current A1C result. The A1C should be used not only to assess the patient’s control over the preceding 2–3 months but also as a check on the accuracy of the meter (or the patient’s self-reported results) and the adequacy of the SMBG testing schedule. Table 7 contains the correlation between A1C levels and mean plasma glucose levels based on data from the DCCT (30).

• Perform the A1C test at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients whose therapy has changed or who are not meeting glycemic goals. (E)

MNT is an integral component of diabetes management and diabetes self-management education. A review of the evidence and detailed information can be found in the ADA technical review and position statement in this area (31,32). People with diabetes should receive individualized MNT as needed to achieve treatment goals, preferably provided by a registered dietitian familiar with the components of diabetes MNT. Goals of MNT that apply to all persons with diabetes are as follows:

• Attain and maintain recommended metabolic outcomes, including glucose and A1C levels; LDL cholesterol, HDL cholesterol, and triglyceride levels; blood pressure; and body weight (see Table 6).

• Prevent and treat the chronic complications and comorbidities of diabetes. Modify nutrient intake and lifestyle as appropriate for the prevention and treatment of obesity, dyslipidemia, CVD, hypertension, and nephropathy.

• Improve health through healthy food choices and physical activity.

• Address individual nutritional needs, taking into consideration personal and cultural preferences and lifestyle while respecting the individual’s wishes and willingness to change.

Goals of MNT that apply to specific situations include the following:

• For youth with type 1 diabetes, provide adequate energy to ensure normal growth and development; integrate insulin regimens into usual eating and physical activity habits.

• For youth with type 2 diabetes, facilitate changes in eating and physical activity habits that reduce insulin resistance and improve metabolic status.

• For pregnant and lactating women, provide adequate energy and nutrients needed for optimal outcomes.

• For older adults, provide for the nutritional and psychosocial needs of an aging individual.

• For individuals treated with insulin or insulin secretagogues, provide self-management education for treatment (and prevention) of hypoglycemia, acute illnesses, and exercise-related blood glucose problems.

• For individuals at risk for diabetes, decrease risk by encouraging physical activity and promoting foods choices that facilitate moderate weight loss or at least prevent weight gain.

Achieving nutrition-related goals requires a coordinated team effort that includes the person with diabetes. Because of the complexity of nutrition issues, it is recommended that a registered dietitian, knowledgeable and skilled in implementing nutrition therapy into diabetes management and education, is the team member who provides MNT. However, it is essential that all team members are knowledgeable about nutrition therapy and are supportive of the person with diabetes who needs to make lifestyle changes.

MNT involves a nutrition assessment to evaluate the patient’s food intake, metabolic status, lifestyle and readiness to make changes, goal setting, dietary instruction and evaluation. To facilitate adherence, the plan should be individualized and take into account cultural, lifestyle, and financial considerations. Monitoring of glucose and A1C, lipids, blood pressure, and renal status is essential to evaluate nutrition-related outcomes. If goals are not met (Table 6), changes must be made in the overall diabetes care and management plan.

• People with 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)

ADA technical reviews on exercise in patients with diabetes have summarized the value of exercise in the diabetes management plan (33,34). Regular exercise has been shown to improve blood glucose control, reduce cardiovascular risk factors, contribute to weight loss, and improve well-being. Furthermore, regular exercise may prevent type 2 diabetes in high-risk individuals (6–8).

Before beginning a physical activity program, the patient with diabetes should have a detailed medical evaluation with appropriate diagnostic studies. This examination should screen for the presence of macro- and microvascular complications that may be worsened by the physical activity program (see next section regarding coronary heart disease [CHD] screening). Identification of areas of concern will allow the design of an individualized physical activity plan that can minimize risk to the patient.

All levels of physical activity, including leisure activities, recreational sports, and competitive professional performance, can be performed by people with diabetes who do not have complications and have good glycemic control. The ability to adjust the therapeutic regimen (insulin therapy and MNT) to allow safe participation is an important management strategy.

• A regular physical activity program, adapted to the presence of complications, is recommended for all patients with diabetes who are capable of participating. (B)

CVD is the major cause of mortality for persons with diabetes. It is also a major contributor to morbidity and direct and indirect costs of diabetes. Type 2 diabetes is an independent risk factor for macrovascular disease, and its common coexisting conditions (e.g., hypertension and dyslipidemia) are also risk factors.

Studies have shown the efficacy of reducing cardiovascular risk factors in preventing or slowing CVD. Evidence is summarized in the following sections and reviewed in detail in the ADA technical reviews on hypertension (35), dyslipidemia (36), aspirin therapy (37), and smoking cessation (38) and in the consensus statement on CHD in people with diabetes (39). Emphasis should be placed on reducing cardiovascular risk factors, when possible, and clinicians should be alert for signs and symptoms of atherosclerosis.

Hypertension (blood pressure ≥140/90 mmHg) is a common comorbidity of diabetes, affecting the majority of people with diabetes, depending on type of diabetes, age, obesity, and ethnicity. Hypertension is also a major risk factor for CVD and microvascular complications such as retinopathy and nephropathy. In type 1 diabetes, hypertension is often the result of underlying nephropathy. In type 2 diabetes, hypertension may be present as part of the metabolic syndrome (i.e., obesity, hyperglycemia, dyslipidemia) that is accompanied by high rates of CVD.

Randomized clinical trials have demonstrated the benefit (reduction of CHD events, stroke, and nephropathy) of lowering blood pressure to <140 mmHg systolic and <80 mmHg diastolic in persons with diabetes (40–43). Epidemiologic analyses show that blood pressures >115/75 mmHg are associated with increased cardiovascular event rates and mortality in persons with diabetes (40,44,45). Therefore, a target blood pressure goal of <130/80 mmHg is reasonable if it can be safely achieved.

Although there are no well-controlled studies of diet and exercise in the treatment of hypertension in persons with diabetes, reducing sodium intake and body weight (when indicated), increasing consumption of fruits, vegetables, and low-fat dairy products, avoiding excessive alcohol consumption, and increasing activity levels have been shown to be effective in reducing blood pressure in nondiabetic individuals (46a). These nonpharmacological strategies may also positively affect glycemia and lipid control. Their effects on cardiovascular events have not been well measured.

Lowering of blood pressure with regimens based on antihypertensive drugs, including ACE inhibitors, angiotensin receptor blockers (ARBs), β-blockers, diuretics, and calcium channel blockers, has been shown to be effective in lowering cardiovascular events. Several studies suggest that ACE inhibitors may be superior to dihydropyridine calcium channel blockers (DCCBs) in reducing cardiovascular events (47,48). Additionally, recent data in people with diabetic nephropathy indicate that ARBs may be superior to DCCBs for reducing cardiovascular events (49). Conversely, in the recently completed International Verapamil Study (INVEST) of more than 22,000 people with coronary artery disease and hypertension, the nondihydropyridine calcium channel blocker, verapamil, demonstrated a similar reduction in cardiovascular mortality to a β-blocker. Moreover, this relationship held true in the diabetic subgroup (49a).

ACE inhibitors have been shown to improve cardiovascular outcomes in high-cardiovascular-risk patients with or without hypertension (50,51). In patients with congestive heart failure, ACE inhibitors are associated with better outcomes when compared with ARBs. ARBs also improve cardiovascular outcomes in the subset of patients with hypertension, diabetes, and end-organ injury (52). The compelling effect of ACE inhibitors or ARBs in patients with albuminuria or renal insufficiency provide additional rationale for use of these agents (see section II below).

The ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a large randomized trial of different initial blood pressure pharmacological therapies, found no large differences between initial therapy with a chlorthalidone, amlodipine and lisinopril. Diuretics appeared slightly more effective than other agents, particularly for reducing heart failure (53). The α-blocker arm of the ALLHAT was terminated after interim analysis showed that doxazosin was substantially less effective in reducing congestive heart failure than diuretic therapy (54).

Before beginning treatment, patients with elevated blood pressures should have their blood pressure reexamined within 1 month to confirm the presence of hypertension. A systolic blood pressure ≥160 mmHg or a diastolic blood pressure ≥100 mmHg, however, mandates that immediate pharmacological therapy be initiated. Patients with hypertension should be seen as often as needed until the recommended blood pressure goal is obtained and then seen as necessary (40). In these patients, other cardiovascular risk factors, including obesity, hyperlipidemia, smoking, presence of microalbuminuria (assessed before initiation of treatment), and glycemic control, should be carefully assessed and treated. Many patients will require three or more drugs to reach target goals.

• Blood pressure should be measured at every routine diabetes visit. Patients found to have systolic blood pressure ≥130 or diastolic blood pressure ≥80 mmHg should have blood pressure confirmed on a separate day. (C)

• Patients with diabetes should be treated to a systolic blood pressure <130 mmHg. (B)

• Patients with diabetes should be treated to a diastolic blood pressure <80 mmHg. (B)

• Patients with hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg) should receive drug therapy in addition to lifestyle and behavioral therapy. (A)

• Multiple drug therapy (two or more agents at proper doses) is generally required to achieve blood pressure targets. (B)

• Patients with a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80–89 mmHg should be given lifestyle and behavioral therapy alone for a maximum of 3 months and then, if targets are not achieved, in addition, be treated with pharmacological agents that block the renin-angiotensin system. (E)

• Initial drug therapy for those with a blood pressure >140/90 mmHg should be with a drug class demonstrated to reduce CVD events in patients with diabetes (ACE inhibitors, ARBs, β-blockers, diuretics, and calcium channel blockers). (A)

• All patients with diabetes and hypertension should be treated with a regimen that includes either an ACE inhibitor or ARB. If one class is not tolerated, the other should be substituted. If needed to achieve blood pressure targets, a thiazide diuretic should be added. (E)

• If ACE inhibitors, ARBs, or diuretics are used, monitor renal function and serum potassium levels. (E)

• While there are no adequate head-to-head comparisons of ACE inhibitors and ARBs, there is clinical trial support for each of the following statements:

  • In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy. (A)

  • In patients with type 2 diabetes, hypertension, and microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria. (A)

  • In those with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency, ARBs have been shown to delay the progression of nephropathy. (A)

• In elderly hypertensive patients, blood pressure should be lowered gradually to avoid complications. (E)

• Patients not achieving target blood pressure despite multiple drug therapy should be referred to a physician experienced in the care of patients with hypertension. (E)

• Orthostatic measurement of blood pressure should be performed in people with diabetes and hypertension when clinically indicated. (E)

Patients with type 2 diabetes have an increased prevalence of lipid abnormalities that contributes to higher rates of CVD. Lipid management aimed at lowering LDL cholesterol, raising HDL cholesterol, and lowering triglycerides has been shown to reduce macrovascular disease and mortality in patients with type 2 diabetes, particularly those who have had prior cardiovascular events.

In studies using HMG (hydroxymethylglutaryl) CoA reductase inhibitors (statins), patients with diabetes achieved significant reductions in coronary and cerebrovascular events (55–58). In two studies using the fibric acid derivative gemfibrozil, reductions in cardiovascular end points were also achieved (59,60).

Target lipid levels are shown in Table 6. Lifestyle intervention including MNT, increased physical activity, weight loss, and smoking cessation should allow some patients to reach these lipid levels. Nutrition intervention should be tailored according to each patient’s age, type of diabetes, pharmacological treatment, lipid levels, and other medical conditions and should focus on the reduction of saturated fat, cholesterol, and transunsaturated fat intake. Glycemic control can also beneficially modify plasma lipid levels. Particularly in patients with very high triglycerides and poor glycemic control, glucose lowering maybe necessary to control hypertriglyceridemia.

Pharmacological treatment is indicated if there is an inadequate response to lifestyle modifications and improved glucose control. However, in patients with clinical CVD and LDL >100 mg/dl, pharmacological therapy should be initiated at the same time that lifestyle intervention is started.

The first priority of pharmacological therapy is to lower LDL cholesterol to a target goal of <100 mg/dl (2.60 mmol/l). For LDL lowering, statins are the drugs of choice (61).

The Heart Protection Study demonstrated that in people with diabetes over the age of 40 with a total cholesterol >135 mg/dl, LDL reduction of ∼30% from baseline with the statin, simvastatin was associated with an ∼25% reduction in the first event rate for major coronary artery events independent of baseline LDL, preexisting vascular disease, type or duration of diabetes, or adequacy of glycemic control (58). Therefore, in patients over the age of 40, statin therapy should be routinely considered. In patients with LDL >130 mg/dl, initial therapy with both lifestyle intervention and a statin is indicated. In patients with LDL between 100 mg/dl (2.60 mmol/l) and 129 mg/dl (3.30 mmol/l), a variety of treatment strategies are available, including more aggressive nutrition intervention or pharmacological treatment with a statin. If the HDL is <40 mg/dl and the LDL is between 100 and 129 mg/dl, a fibric acid derivative or niacin might be used.

Niacin is the most effective drug for raising HDL but can significantly increase blood glucose at a high dose. More recent studies demonstrate that at modest doses (750–2,000 mg/day), significant benefit with regards to LDL, HDL, and triglyceride levels are accompanied by modest changes in glucose that are generally amenable to adjustment of diabetes therapy (62,63).

Combination therapy, with a statin and a fibrate or statin and niacin, may be efficacious for patients needing treatment for all three lipid fractions, but this combination is associated with an increased risk for abnormal transaminase levels, myositis, or rhabdomyolysis. The risk of rhabdomyolysis seems to be lower when statins are combined with fenofibrate than gemfibrozil.

In children and adolescentswith diabetes, LDL cholesterol should be lowered to <100 mg/dl (2.60 mmol/l) using diet and medications based on LDL level and other cardiovascular risk factors in addition to diabetes (64,65).

• In adult patients, test for lipid disorders at least annually and more often if needed to achieve goals. In adults with low-risk lipid values (LDL <100 mg/dl, HDL >50 mg/dl, and triglycerides <150 mg/dl), repeat lipid assessments every 2 years. (E)

• In children >2 years of age, perform a lipid profile after diagnosis of diabetes and when glucose control has been established.

  • Type 1 diabetes: Begin prior to puberty, if positive family history of CVD (or if family history is unknown), and at puberty, if family history is known and is negative.

  • Type 2 diabetes: Begin at diagnosis, regardless of pubertal status.

  • If lipid values are considered low risk, repeat lipid profile every 2–5 years based on CVD risk status.

• Lifestyle modification focusing on the reduction of saturated fat and cholesterol intake, weight loss, increased physical activity, and smoking cessation has been shown to improve the lipid profile in patients with diabetes. (A)

• Patients who do not achieve lipid goals with lifestyle modifications require pharmacological therapy. (A)

• Lower LDL cholesterol to <100 mg/dl (2.6 mmol/l) as the primary goal of therapy for adults. (B)

• Lowering LDL cholesterol with a statin is associated with a reduction in cardiovascular events. (A)

• In people with diabetes over the age of 40 with a total cholesterol ≥135 mg/dl, statin therapy to achieve an LDL reduction of ∼30% regardless of baseline LDL levels may be appropriate. (A)

• In children and adolescents with diabetes, LDL cholesterol should be lowered to <100 mg/dl (2.60 mmol/l) using diet as well as medications based on LDL level and other cardiovascular risk factors in addition to diabetes. (E)

• Lower triglycerides to <150 mg/dl (1.7 mmol/l) and raise HDL cholesterol to >40 mg/dl (1.15 mmol/l). In women, an HDL goal 10 mg/dl higher may be appropriate. (C)

• Lowering triglycerides and increasing HDL cholesterol with a fibrate are associated with a reduction in cardiovascular events in patients with clinical CVD, low HDL and near-normal levels of LDL. (A)

• Combination therapy employing statins and fibrates or niacin may be necessary to achieve lipid targets, but have not been evaluated in outcomes studies for either event reduction or safety. (E)

The use of aspirin in diabetes is reviewed in detail in the ADA technical review (37) and position statement (66) on aspirin therapy. Aspirin has been recommended as a primary (66a,66b) and secondary therapy to prevent cardiovascular events in diabetic and nondiabetic individuals. One large meta-analysis and several clinical trials demonstrate the efficacy of using aspirin as a preventive measure for cardiovascular events, including stroke and myocardial infarction. Many trials have shown an ∼30% decrease in myocardial infarction and a 20% decrease in stroke in a wide range of patients, including young and middle-aged patients, patients with and without a history of CVD, males and females, and patients with hypertension.

Dosages used in most clinical trials ranged from 75 to 325 mg/day. There is no evidence to support any specific dose, but using the lowest possible dosage may help reduce side effects. There is no evidence for a specific age at which to start aspirin, but at ages below 30 years, aspirin has not been studied.

Clopidogrel has been demonstrated to reduce CVD rates in diabetic individuals (67). Adjunctive therapy in very high-risk patients or as alternative therapy in aspirin-intolerant patients should be considered.

• Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in those with diabetes with a history of myocardial infarction, vascular bypass procedure, stroke or transient ischemic attack, peripheral vascular disease, claudication, and/or angina. (A)

• Use aspirin therapy (75–162 mg/day) as a primary prevention strategy in those with type 2 diabetes at increased cardiovascular risk, including those who are over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, albuminuria). (A)

• Use aspirin therapy (75–162 mg/day) as a primary prevention strategy in those with type 1 diabetes at increased cardiovascular risk, including those who are over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, albuminuria). (C)

• People with aspirin allergy, bleeding tendency, receiving anticoagulant therapy, recent gastrointestinal bleeding, and clinically active hepatic disease are not candidates for aspirin therapy. Other antiplatelet agents may be a reasonable alternative for patients with high risk. (E)

• Aspirin therapy should not be recommended for patients under the age of 21 years because of the increased risk of Reye’s syndrome associated with aspirin use in this population. People under the age of 30 have not been studied. (E)

Issues of smoking in diabetes are reviewed in detail in the ADA technical review (38) and position statement (68) on smoking cessation. A large body of evidence from epidemiological, case-control, and cohort studies provides convincing documentation of the causal link between cigarette smoking and health risks. Cigarette smoking contributes to one of every five deaths in the U.S. and is the most important modifiable cause of premature death. Much of the prior work documenting the impact of smoking on health did not separately discuss results on subsets of individuals with diabetes, suggesting that the identified risks are at least equivalent to those found in the general population. Other studies of individuals with diabetes consistently found a heightened risk of morbidity and premature death associated with the development of macrovascular complications among smokers. Smoking is also related to the premature development of microvascular complications of diabetes and may have a role in the development of type 2 diabetes.

A number of large randomized clinical trials have demonstrated the efficacy and cost-effectiveness of counseling in changing smoking behavior. Such studies, combined with others specific to individuals with diabetes, suggest that smoking cessation counseling is effective in reducing tobacco use (69,70).

The routine and thorough assessment of tobacco use is important as a means of preventing smoking or encouraging cessation. Special considerations should include assessment of level of nicotine dependence, which is associated with difficulty in quitting and relapse.

• Advise all patients not to smoke. (A)

• Include smoking cessation counseling and other forms of treatment as a routine component of diabetes care. (B)

CHD screening and treatment are reviewed in detail in the ADA consensus statement on CHD in people with diabetes (39). To identify the presence of CHD in diabetic patients without clear or suggestive symptoms of coronary artery disease (CAD), a risk factor-based approach to the initial diagnostic evaluation and subsequent follow-up is recommended. At least annually, cardiovascular risk factors should be assessed. These risk factors include dyslipidemia, hypertension, smoking, a positive family history of premature coronary disease, and the presence of micro- or macroalbuminuria. Abnormal risk factors should be treated as described elsewhere in these guidelines. Patients at increased CHD risk should receive aspirin and may warrant an ACE inhibitor.

Candidates for a diagnostic cardiac stress test include those with 1) typical or atypical cardiac symptoms and 2) an abnormal resting electrocardiogram (ECG). Candidates for a screening cardiac stress test include those with 1) a history of peripheral or carotid occlusive disease; 2) sedentary lifestyle, age >35 years, and plans to begin a vigorous exercise program; and 3) two or more of the risk factors noted above.

Current evidence suggests that noninvasive tests can improve assessment of future CHD risk. There is, however, no current evidence that such testing in asymptomatic patients with risk factors improves outcomes or leads to better utilization of treatments.

Patients with abnormal exercise ECG and patients unable to perform an exercise ECG require additional or alternative testing. Currently, stress nuclear perfusion and stress echocardiography are valuable next-level diagnostic procedures. A consultation with a cardiologist is recommended regarding further work-up.

• Perform exercise stress testing in asymptomatic diabetic patients based on the criteria outlined above. Consider a risk factor-based strategy for the diagnosis of CAD that might include stress ECG and/or stress echocardiography and/or perfusion imaging. (E)

• Refer patients with signs and symptoms of CVD or with positive noninvasive test for CAD to a cardiologist for further evaluation. (E)

• In patients with treated congestive heart failure, metformin use is contraindicated. The thiazolidinediones are associated with fluid retention, and their use can be complicated by the development of congestive heart failure. Caution in prescribing thiazolidinediones in the setting of known congestive heart failure or other heart diseases as well as in patients with preexisting edema or concurrent insulin therapy is required. (E)

• In patients >55 years of age, with or without hypertension but with another cardiovascular risk factor (history of CVD, dyslipidemia, microalbuminuria, smoking), an ACE inhibitor (if not contraindicated) should be considered to reduce the risk of cardiovascular events. (A)

• In patients with a prior myocardial infarction or in patients undergoing major surgery, β-blockers, in addition, should be considered to reduce mortality. (A)

Diabetic nephropathy occurs in 20–40% of patients with diabetes and is the single leading cause of end-stage renal disease (ESRD). Persistent albuminuria in the range of 30–299 mg/24 h (microalbuminuria) has been shown to be the earliest stage of diabetic nephropathy in type 1 diabetes and a marker for development of nephropathy in type 2 diabetes. Microalbuminuria is also a well-established marker of increased CVD risk (71).

Patients with microalbuminuria who progress to macroalbuminuria (≥300 mg/24 h) are likely to progress to ESRD over a period of years (72,73). Over the past several years, a number of interventions have been demonstrated to reduce the risk and slow the progression of renal disease.

Intensive diabetes management with the goal of achieving near normoglycemia has been shown in large prospective randomized studies to delay the onset of microalbuminuria and the progression of micro- to macroalbuminuria in patients with type 1 (74,75) and type 2 diabetes (16). The UKPDS provided strong evidence that control of blood pressure can reduce the development of nephropathy (41). In addition, large prospective randomized studies in patients with type 1 diabetes have demonstrated that achievement of lower levels of systolic blood pressure (<140 mmHg) achieved with treatment using ACE inhibitors provides a selective benefit over other antihypertensive drug classes in delaying the progression from micro- to macroalbuminuria and can slow the decline in glomerular filtration rate (GFR) in patients with macroalbuminuria (41,76–78).

In addition, ACE inhibitors have been shown to reduce severe CVD (i.e., myocardial infarction, stroke, death), thus further supporting the use of these agents in patients with microalbuminuria (50). ARBs have also been shown to reduce the rate of progression from micro- to macroalbuminuria as well as ESRD in patients with type 2 diabetes (79–81). Some evidence suggests that ARBs have a smaller magnitude of rise in potassium compared with ACE inhibitors in people with nephropathy (82). With regards to slowing the progression of nephropathy, the use of DCCBs as initial therapy is not more effective than placebo. Their use in nephropathy should be restricted to additional therapy to further lower blood pressure in patients already treated with ACE inhibitors or ARBs (49). In the setting of albuminuria or nephropathy, in patients unable to tolerate ACE inhibitors and/or ARBs, consider the use of non-DCCBs, β-blockers, or diuretics for the management of blood pressure (83,84).

A meta-analysis of several small studies has shown that protein restriction may be of benefit in some patients whose nephropathy seems to be progressing despite optimal glucose and blood pressure control (85).

Screening for microalbuminuria can be performed by three methods: 1) measurement of the albumin-to-creatinine ratio in a random, spot collection (preferred method); 2) 24-h collection with creatinine, allowing the simultaneous measurement of creatinine clearance; and 3) timed (e.g., 4-h or overnight) collection.

The analysis of a spot sample for the albumin-to-creatinine ratio is strongly recommended by most authorities (86,87). The other two alternatives (24-h collection and a timed specimen) are rarely necessary. Measurement of a spot urine microalbumin by immunoassay or by using a dipstick test specific for microalbumin without simultaneously measuring urine creatinine is less expensive than the recommended methods, but is susceptible to false-negative and false-positive determinations as a result of variation in urine concentration due to hydration and other factors.

At least two of three tests measured within a 6-month period should show elevated levels before a patient is designated as having microalbuminuria. Abnormalities of albumin excretion are defined in Table 8.

Physicians may use the Levey modification of the Cockcroft and Gault equation to calculate estimated GFR (eGFR) from serum creatinine and to stage the patient’s renal disease (87,88). The eGFR can easily be calculated by going to www.kidney.org/professionals/dogi/gfr_calculator.cfm.

The role of annual microalbumuria assessment is less clear after diagnosis of microalbuminuria and institution of ACE inhibitor or ARB therapy and blood pressure control. Most experts, however, recommend continued surveillance to assess both response to therapy and progression of disease. Many experts suggest that managing urine microalbuminuria to reduce it to the normal or near-normal range may improve renal and cardiovascular prognosis; this approach has not been formally evaluated in prospective trials.

Consider referral to a physician experienced in the care of diabetic renal disease either when the GFR has fallen to <60 ml · min⁻¹ · 1.73 m⁻² or if difficulties occur in the management of hypertension or hyperkalemia. It is suggested that consultation with a nephrologist be obtained when the GFR is <30 ml · min⁻¹ · 1.73 m⁻². Early referral of such patients has been found to reduce cost and improve quality of care and keep people off dialysis longer (89). For a complete discussion on the treatment of nephropathy, see the ADA’s position statement “Diabetic Nephropathy” (90).

• To reduce the risk and/or slow the progression of nephropathy, optimize glucose control. (A)

• To reduce the risk and/or slow the progression of nephropathy, optimize blood pressure control. (A)

• Perform an annual test for the presence of microalbuminuria in type 1 diabetic patients with diabetes duration of ≥5 years and in all type 2 diabetic patients, starting at diagnosis. (E)

• In the treatment of both micro- and macroalbuminuria, either ACE inhibitors or ARBs should be used. (A)

• While there are no adequate head-to-head comparisons of ACE inhibitors and ARBs, there is clinical trial support for each of the following statements:

  • In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy. (A)

  • In patients with type 2 diabetes, hypertension, and microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria. (A)

  • In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dl), ARBs have been shown to delay the progression of nephropathy. (A)

  • If one class is not tolerated, the other should be substituted. (E)

• With presence of nephropathy, initiate protein restriction to ≤0.8 g · kg⁻¹ body wt⁻¹ · day⁻¹ (∼10% of daily calories), the current adult-recommended dietary allowance for protein. Further restriction may be useful in slowing the decline of GFR in selected patients. (B)

• With regards to slowing the progression of nephropathy, the use of DCCBs as initial therapy is not more effective than placebo. Their use in nephropathy should be restricted to additional therapy to further lower blood pressure in patients already treated with ACE inhibitors or ARBs. (B)

• In the setting of albuminuria or nephropathy, in patients unable to tolerate ACE inhibitors and/or ARBs, consider the use of non-DCCBs, β-blockers, or diuretics for the management of blood pressure. (E)

• If ACE inhibitors, ARBs, or diuretics are used, monitor serum potassium levels for the development of hyperkalemia. (B)

• Consider referral to a physician experienced in the care of diabetic renal disease when the eGFR has fallen to <60 ml · min⁻¹ · 1.73 m⁻² or if difficulties occur in the management of hypertension or hyperkalemia. (B)

Diabetic retinopathy is a highly specific vascular complication of both type 1 and type 2 diabetes. The prevalence of retinopathy is strongly related to the duration of diabetes. Diabetic retinopathy is estimated to be the most frequent cause of new cases of blindness among adults aged 20–74 years.

Intensive diabetes management with the goal of achieving near normoglycemia has been shown in large prospective randomized studies to prevent and/or delay the onset of diabetic retinopathy (15,16). In addition to glycemic control, several other factors seem to increase the risk of retinopathy. The presence of nephropathy is associated with retinopathy. High blood pressure is an established risk factor for the development of macular edema and is associated with the presence of proliferative diabetic retinopathy (PDR). Lowering blood pressure, as demonstrated by the UKPDS, has been shown to decrease the progression of retinopathy. Several case series and a controlled prospective study suggest that pregnancy in type 1 diabetic patients may aggravate retinopathy (91). During pregnancy and 1 year postpartum, retinopathy may be transiently aggravated; laser photocoagulation surgery can minimize this risk (92).

Patients with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 3–5 years after the onset of diabetes. Patients with type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes. Subsequent examinations for type 1 and type 2 diabetic patients should be repeated annually by an ophthalmologist or optometrist who is knowledgeable and experienced in diagnosing the presence of diabetic retinopathy and is aware of its management. Less frequent exams (every 2–3 years) may be considered with the advice of an eye care professional in the setting of a normal eye exam (93–95). Examinations will be required more frequently if retinopathy is progressing.

One of the main motivations for screening for diabetic retinopathy is the established efficacy of laser photocoagulation surgery in preventing visual loss. Two large National Institutes of Health-sponsored trials, the Diabetic Retinopathy Study (DRS) (96–100) and the Early Treatment Diabetic Retinopathy Study (ETDRS), provide the strongest support for the therapeutic benefit of photocoagulation surgery (101–107).

The DRS tested whether scatter (panretinal) photocoagulation surgery could reduce the risk of vision loss from PDR. Severe visual loss (i.e., best acuity of 5/200 or worse) was seen in 15.9% of untreated vs. 6.4% of treated eyes. The benefit was greatest among patients whose baseline evaluation revealed high-risk characteristics (HRCs) (chiefly disc neovascularization or vitreous hemorrhage with any retinal neovascularization). Of control eyes with HRCs, 26% progressed to severe visual loss vs. 11% of treated eyes. Given the risk of a modest loss of visual acuity and of contraction of visual field from panretinal laser surgery, such therapy has been primarily recommended for eyes approaching or reaching HRCs.

The ETDRS established the benefit of focal laser photocoagulation surgery in eyes with macular edema, particularly those with clinically significant macular edema. In patients with clinically significant macular edema after 2 years, 20% of untreated eyes had a doubling of the visual angle (e.g., 20/50 to 20/100) compared with 8% of treated eyes. Other results from the ETDRS indicate that, provided careful follow-up can be maintained, scatter photocoagulation surgery is not recommended for eyes with mild or moderate nonproliferative diabetic retinopathy (NPDR). When retinopathy is more severe, scatter photocoagulation surgery should be considered, and usually should not be delayed, if the eye has reached the high-risk proliferative stage. In older-onset patients with severe NPDR or less than high-risk PDR, the risk of severe visual loss and vitrectomy is reduced ∼50% by laser photocoagulation surgery at these earlier stages.

Laser photocoagulation surgery in both the DRS and the ETDRS was beneficial in reducing the risk of further visual loss, but generally not beneficial in reversing already diminished acuity. This preventive effect and the fact that patients with PDR or macular edema may be asymptomatic provide strong support for a screening program to detect diabetic retinopathy.

For a detailed review of the evidence and further discussion, see the ADA’s technical review and position statement on this subject (91,108,109).

• Optimal glycemic control can substantially reduce the risk and progression of diabetic retinopathy. (A)

• Optimal blood pressure control can reduce the risk and progression of diabetic retinopathy. (A)

• Aspirin therapy does not prevent retinopathy or increase the risks of hemorrhage. (A)

• Adults and adolescents with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 3–5 years after the onset of diabetes. (B)

• Patients with type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes. (B)

• Subsequent examinations for type 1 and type 2 diabetic patients should be repeated annually by an ophthalmologist or optometrist who is knowledgeable and experienced in diagnosing the presence of diabetic retinopathy and is aware of its management. Less frequent exams (every 2–3 years) may be considered with the advice of an eye care professional in the setting of a normal eye exam. Examinations will be required more frequently if retinopathy is progressing. (B)

• When planning pregnancy, women with preexisting diabetes should have a comprehensive eye examination and should be counseled on the risk of development and/or progression of diabetic retinopathy. Women with diabetes who become pregnant should have a comprehensive eye examination in the first trimester and close follow-up throughout pregnancy and for 1 year postpartum. This guideline does not apply to women who develop GDM because such individuals are not at increased risk for diabetic retinopathy. (B)

• Laser therapy can reduce the risk of vision loss in patients with HRCs. (A)

• Promptly refer patients with any level of macular edema, severe NPDR, or any PDR to an ophthalmologist who is knowledgeable and experienced in the management and treatment of diabetic retinopathy. (A)

Amputation and foot ulceration are the most common consequences of diabetic neuropathy and major causes of morbidity and disability in people with diabetes. Early recognition and management of independent risk factors can prevent or delay adverse outcomes.

The risk of ulcers or amputations is increased in people who have had diabetes >10 years, are male, have poor glucose control, or have cardiovascular, retinal, or renal complications. The following foot-related risk conditions are associated with an increased risk of amputation:

• Peripheral neuropathy with loss of protective sensation.

• Altered biomechanics (in the presence of neuropathy).

• Evidence of increased pressure (erythema, hemorrhage under a callus).

• Bony deformity.

• Peripheral vascular disease (decreased or absent pedal pulses).

• A history of ulcers or amputation.

• Severe nail pathology.

All individuals with diabetes should receive an annual foot examination to identify high-risk foot conditions. This examination should include assessment of protective sensation, foot structure and biomechanics, vascular status, and skin integrity. People with one or more high-risk foot conditions should be evaluated more frequently for the development of additional risk factors. People with neuropathy should have a visual inspection of their feet at every visit with a health care professional. Evaluation of neurological status in the low-risk foot should include a quantitative somatosensory threshold test, using the Semmes-Weinstein 5.07 (10-g) monofilament. The skin should be assessed for integrity, especially between the toes and under the metatarsal heads. The presence of erythema, warmth, or callus formation may indicate areas of tissue damage with impending breakdown. Bony deformities, limitation in joint mobility, and problems with gait and balance should be assessed.

People with neuropathy or evidence of increased plantar pressure may be adequately managed with well-fitted walking shoes or athletic shoes. Patients should be educated on the implications of sensory loss and the ways to substitute other sensory modalities (hand palpation, visual inspection) for surveillance of early problems. People with evidence of increased plantar pressure (e.g., erythema, warmth, callus, or measured pressure) should use footwear that cushions and redistributes the pressure. Callus can be debrided with a scalpel by a foot care specialist or other health professional with experience and training in foot care. People with bony deformities (e.g., hammertoes, prominent metatarsal heads, bunions) may need extra-wide shoes or depth shoes. People with extreme bony deformities (e.g., Charcot foot) that cannot be accommodated with commercial therapeutic footwear may need custom-molded shoes.

Initial screening for peripheral arterial disease (PAD) should include a history for claudication and an assessment of the pedal pulses. Consider obtaining an ankle-brachial index (ABI), as many patients with PAD are asymptomatic. Refer patients with significant or a positive ABI for further vascular assessment and consider exercise, medications, and surgical options (110).

Patients with diabetes and high-risk foot conditions should be educated regarding their risk factors and appropriate management. Patients at risk should understand the implications of the loss of protective sensation, the importance of foot monitoring on a daily basis, the proper care of the foot, including nail and skin care, and the selection of appropriate footwear. The patient’s understanding of these issues and their physical ability to conduct proper foot surveillance and care should be assessed. Patients with visual difficulties, physical constraints preventing movement, or cognitive problems that impair their ability to assess the condition of the foot and to institute appropriate responses will need other people, such as family members, to assist in their care. Patients at low risk may benefit from education on foot care and footwear.

For a detailed review of the evidence and further discussion, see the ADA’s technical review and position statement in this area (111,112).

Problems involving the feet, especially ulcers and wound care, may require care by a podiatrist, orthopedic surgeon, or rehabilitation specialist experienced in the management of persons with diabetes. For a complete discussion on wound care, see the ADA’s consensus statement on diabetic foot wound care (113).

• A multidisciplinary approach is recommended for persons with foot ulcers and high-risk feet, especially those with a history of prior ulcer or amputation. (A)

• The foot examination can be accomplished in a primary care setting and should include the use of a Semmes-Weinstein monofilament, tuning fork, palpation, and a visual examination. (B)

• Educate all patients, especially those with risk factors, including smoking, or prior lower-extremity complications, about the risk and prevention of foot problems and reinforce self-care behavior. (B)

• Refer high-risk patients to foot care specialists for ongoing preventive care and life-long surveillance. (C)

• Initial screening for PAD should include a history for claudication and an assessment of the pedal pulses. Consider obtaining an ABI, as many patients with PAD are asymptomatic. (C)

• Refer patients with significant claudication or a positive ABI for further vascular assessment and consider exercise, medications, and surgical options. (C)

• Perform a comprehensive foot examination annually on patients with diabetes to identify risk factors predictive of ulcers and amputations. Perform a visual inspection of patients’ feet at each routine visit. (E)

Major congenital malformations remain the leading cause of mortality and serious morbidity in infants of mothers with type 1 and type 2 diabetes. Observational studies indicate that the risk of malformations increases continuously with increasing maternal glycemia during the first 6–8 weeks of gestation, as defined by first trimester A1C concentrations. There is no threshold for A1C values above which the risk begins or below which it disappears. However, malformation rates above the 1–2% background rate seen in nondiabetic pregnancies appear to be limited to pregnancies in which first trimester A1C concentrations are >1% above the normal range.

Preconception care of diabetes appears to reduce the risk of congenital malformations. Five nonrandomized studies have compared rates of major malformations in infants between women who participated in preconception diabetes care programs and women who initiated intensive diabetes management after they were already pregnant. The preconception care programs were multidisciplinary and designed to train patients in diabetes self-management with diet, intensified insulin therapy, and SMBG. Goals were set to achieve normal blood glucose concentrations, and >80% of subjects achieved normal A1C concentrations before they became pregnant (114–118). In all five studies, the incidence of major congenital malformations in women who participated in preconception care (range 1.0–1.7% of infants) was much lower than the incidence in women who did not participate (range 1.4–10.9% of infants). One limitation of these studies is that participation in preconception care was self-selected by patients rather than randomized. Thus, it is impossible to be certain that the lower malformation rates resulted fully from improved diabetes care. Nonetheless, the overwhelming evidence supports the concept that malformations can be reduced or prevented by careful management of diabetes before pregnancy.

Planned pregnancies greatly facilitate preconception diabetes care. Unfortunately, nearly two-thirds of pregnancies in women with diabetes are unplanned, leading to a persistent excess of malformations in infants of diabetic mothers. To minimize the occurrence of these devastating malformations, standard care for all women with diabetes who have child-bearing potential should include 1) education about the risk of malformations associated with unplanned pregnancies and poor metabolic control and 2) use of effective contraception at all times, unless the patient is in good metabolic control and actively trying to conceive.

Women contemplating pregnancy need to be seen frequently by a multidisciplinary team experienced in the management of diabetes before and during pregnancy. Teams may vary but should include a diabetologist, an internist or a family physician, an obstetrician, a diabetes educator, a dietitian, a social worker, and other specialists as necessary. The goals of preconception care are to 1) integrate the patient into the management of her diabetes, 2) achieve the lowest A1C test results possible without excessive hypoglycemia, 3) assure effective contraception until stable and acceptable glycemia is achieved, and 4) identify, evaluate, and treat long-term diabetic complications such as retinopathy, nephropathy, neuropathy, hypertension, and CAD.

For further discussion, see the ADA’s technical review and position statement on this subject (119,120).

• A1C levels should be normal or as close to normal as possible (<1% above the upper limits of normal) in an individual patient before conception is attempted. (B)

• All women with diabetes and child-bearing potential should be educated about the need for good glucose control before pregnancy. They should participate in family planning. (E)

• Women with diabetes who are contemplating pregnancy should be evaluated and, if indicated, treated for diabetic retinopathy, nephropathy, neuropathy, and CVD. (E)

• Among the drugs commonly used in the treatment of patients with diabetes, statins are pregnancy category X and should be discontinued before conception if possible. ACE inhibitors and ARBs are category C in the first trimester (maternal benefit may outweigh fetal risk in certain situations), but category D in later pregnancy, and should generally be discontinued before pregnancy. Among the oral antidiabetic agents, metformin and acarbose are classified as category B and all others as category C; potential risks and benefits of oral antidiabetic agents in the preconception period must be carefully weighed, recognizing that sufficient data are not available to establish the safety of these agents in pregnancy. They should generally be discontinued in pregnancy. (E)

Influenza and pneumonia are common, preventable infectious diseases associated with high mortality and morbidity in the elderly and in people with chronic diseases. There are limited studies reporting the morbidity and mortality of influenza and pneumococcal pneumonia specifically in people with diabetes. Observational studies of patients with a variety of chronic illnesses, including diabetes, show that these conditions are associated with an increase in hospitalizations for influenza and its complications. Based on a case-control series, influenza vaccine has been shown to reduce diabetes-related hospital admission by as much as 79% during flu epidemics (121). People with diabetes may be at increased risk of the bacteremic form of pneumococcal infection and have been reported to have a high risk of nosocomial bacteremia, which has a mortality rate as high as 50%.

Safe and effective vaccines are available that can greatly reduce the risk of serious complications from these diseases (122,123). There is sufficient evidence to support that people with diabetes have appropriate serologic and clinical responses to these vaccinations. The Centers for Disease Control’s Advisory Committee on Immunization Practices recommends influenza and pneumococcal vaccines for all persons over 65 years of age as well as for all persons of any age with diabetes.

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 (124,125).

• Annually provide an influenza vaccine to all diabetic patients 6 months of age or older. (C)

• Provide at least one lifetime pneumococcal vaccine for adults with diabetes. A one-time revaccination is recommended for individuals >64 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)

Diabetes is an important health condition for the aging population; at least 20% of patients over the age of 65 years have diabetes. The number of older persons with diabetes can be expected to grow rapidly over the coming decades. A recent publication, “Guidelines for improving the care of the older person with diabetes,” contains evidence-based guidelines produced in conjunction with the American Geriatric Society. This document contains an excellent discussion of this area, and specific guidelines and language from it have been incorporated below (126). Unfortunately, there are no long-term studies in persons over 65 years of age demonstrating the benefits of tight glycemic control, blood pressure, and lipid control. Older persons with diabetes have higher rates of premature death, functional disability, and coexisting illnesses such as hypertension, CHD, and stroke than those without diabetes. Older adults with diabetes are also at greater risk than other older persons for several common geriatric syndromes, such as polypharmacy, depression, cognitive impairment, urinary incontinence, injurious falls, and persistent pain.

The care of older adults with diabetes is complicated by their clinical and functional heterogeneity. Some older persons developed diabetes in middle age and face years of comorbidity; others who are newly diagnosed may have had years of undiagnosed comorbidity or few complications from the disease. Some older adults with diabetes are frail and have other underlying chronic conditions, substantial diabetes-related comorbidity, or limited physical or cognitive functioning, but other older persons with diabetes have little comorbidity and are active. Life expectancies are also highly variable for this population. Clinicians caring for older adults with diabetes must take this heterogeneity into consideration when setting and prioritizing treatment goals.

All this having been said, patients who can be expected to live long enough to reap the benefits of long-term intensive diabetes management (∼10 years) and who are active, cognitively intact, and willing to undertake the responsibility of self-management should be encouraged to do so and be treated using the stated goals for younger adults with diabetes.

There is good evidence from middle-aged and older adults suggesting that multidisciplinary interventions that provide education on medication use, monitoring, and recognizing hypo- and hyperglycemia can significantly improve glycemic control. Although control of hyperglycemia is important, in older persons with diabetes, greater reductions in morbidity and mortality may result from control of all cardiovascular risk factors rather than from tight glycemic control alone. There is strong evidence from clinical trials of the value of treating hypertension in the elderly. There is less evidence for lipid-lowering and aspirin therapy, although as diabetic patients have such an elevated risk for CVD, aggressive management of lipids and aspirin use when not contraindicated are reasonable interventions.

As noted above, for patients with advanced diabetes complications, life-limiting comorbid illness, or cognitive or functional impairment, it is reasonable to set less intensive glycemic target goals. These patients are less likely to benefit from reducing the risk of microvascular complications and more likely to suffer serious adverse effects from hypoglycemia. Patients with poorly controlled diabetes may be subject to acute complications of diabetes, including hyperglycemic hyperosmolar coma. Older patients can be treated with the same drug regimens as younger patients, but special care is required in prescribing and monitoring drug therapy. Metformin is often contraindicated because of renal insufficiency or heart failure. Sulfonylureas and other insulin secretagogues can cause hypoglycemia. Insulin can also cause hypoglycemia as well as require good visual and motor skills and cognitive ability of the patient or a caregiver. Thiazolidinediones should not be used in patients with congestive heart failure (New York Heart Association [NYHA] Class III and IV). Drugs should be started at the lowest dose and titrated up gradually until targets are reached or side effects develop. As well as regards blood pressure and lipid management, the potential benefits must always be weighed against potential risks.

Approximately three-quarters of all newly diagnosed cases of type 1 diabetes occur in individuals younger than 18 years of age. Care of this group requires integration of diabetes management with the complicated physical and emotional growth needs of children, adolescents, and their families.

Diabetes care for children of this age-group should be provided by a team that can deal with these special medical, educational, nutritional, and behavioral issues.

At the time of initial diagnosis, it is extremely important to establish the goals of care and to begin diabetes self-management education. A firm educational base should be provided so that the individual and family can become increasingly independent in the self-management of diabetes. Glycemic goals may need to be modified to take into account the fact that most children younger than 6 or 7 years of age have a form of “hypoglycemic unawareness,” in that they lack the cognitive capacity to recognize and respond to hypoglycemic symptoms and may be at greater risk for the sequelae of hypoglycemia.

Intercurrent illnesses are more frequent in young children. Sick-day management rules, including assessment for ketosis with every illness, must be established and taught to prevent severe hyperglycemia and DKA that requires hospitalization and may lead to severe morbidity and even death (24). MNT should be provided at diagnosis, and at least annually thereafter, by an individual experienced with the nutritional needs of the growing child and the behavioral issues that have an impact on adolescent diets. Caution must be exercised to avoid overaggressive dietary manipulation in the very young. Assessment of lifestyle needs should be accompanied by possible modifications of the diabetes regimen. For example, an adolescent who requires more flexibility might be switched to a basal/bolus insulin program with preprandial rapidly acting insulin administration or continuous subcutaneous insulin injection (CSII).

A major issue deserving emphasis in this age-group is that of “adherence.” No matter how sound the medical regimen, it can only be as good as the ability of the family and/or individual to implement it. Family involvement in diabetes remains an important component of optimal diabetes management throughout childhood and into adolescence. Health care providers who care for children and adolescents, therefore, must be capable of evaluating the behavioral, emotional, and psychosocial factors that interfere with implementation and then must work with the individual and family to resolve problems that occur and/or to modify goals as appropriate.

The incidence of type 2 diabetes in children and adolescents has been shown to be increasing, especially in ethnic minority populations (127,128). Although there are insufficient data to make definite recommendations, a recent ADA consensus statement provides guidance to the prevention, screening, and treatment of type 2 diabetes in young people. The ideal goal of treatment is normalization of blood glucose and A1C values. Accurate diagnosis and classification of diabetes is crucial in determining appropriate treatment for these patients. Medical management should include MNT, exercise, and lifestyle interventions, but drug therapy, including insulin in many cases, is required. Successful control of comorbidities, such as hypertension and hyperlipidemia, is also important. For further discussion, see the ADA consensus statement “Type 2 Diabetes in Children and Adolescents” (13).

Information should be supplied to the school or day care setting so that school personnel are aware of the diagnosis of diabetes in the student and of the signs, symptoms, and treatment of hypoglycemia. It is desirable that blood glucose testing be performed at the school or day care setting before lunch and when signs or symptoms of abnormal blood glucose levels are present. Many children may require support for insulin administration by either injection or CSII before lunch at school or in day care.

For further discussion, see the ADA’s position statement “The Care of Children With Diabetes in the School and Day Care Setting” (129) and the NDEP publication “Helping the Student with Diabetes Succeed: A Guide for School Personnel” (National Diabetes Education Program, 2003, www.ndep.nih.gov).

The implementation of the standards of care for diabetes is suboptimal in the health care system. The challenge of providing effective diabetes care has thus far defied a simple solution, yet numerous interventions have been implemented with strategies to improve adherence to the recommended standards. Successful programs have published results showing improvement in important outcomes such as A1C measurements as well as process measures such as provision of eye exams. The interventions have been focused at this level of providers, the system, and patients. Features of successful programs reported in the literature include:

• Improving provider education regarding the standards of care through formal and informal provider education program.

• Adoption of practice guidelines, with participation of the providers in the process. Guidelines should be readily accessible at the point of service, such as on patient charts, in examining rooms, or on office computer systems.

• Use of checklists that mirror guidelines have been successful at improving adherence to standard of care.

• Systems changes, such as provision of automated reminders to providers and patients, profiling or reporting of data to providers, and identification of patients at risk because of abnormal target values or a lack of reported values.

• Quality improvement programs combining CQI or other cycles of analysis and intervention with provider performance data.

• Practice changes, such as clustering of dedicated diabetes visits and group visits.

• Tracking systems either with an electronic medical record or patient registry have been helpful at increasing adherence to standards of care.

• Delivery of diabetes self-management education has been shown to increase adherence to standard of care.

• Availability of case management services, usually by a nurse. Nurses using detailed protocols working under the supervision of physicians. Nurse education calls have been helpful.

• Availability and involvement of expert consultants, such as endocrinologists and diabetes educators.

• Clustering patients with diabetes into specific times within a primary care practice schedule.

• Other nonautomated systems such as mailing reminders to patients, chart stickers, and flow sheets have been useful to prompt both providers and patients.

Because these interventions are generally provided as components of a multifactorial intervention, it is difficult to assess the contribution of each component; however, it is clear that optimal diabetes management requires an organized, systematic approach and involvement of a health care team. Further research to identify improved mechanisms to translate research into practice is necessary. Successful translation will require a multidiscipline approach utilizing a variety of behavioral and technological approaches.

In recent years, numerous health care organizations, ranging from large health care systems such as the U.S. Veteran’s Administration to small private practices, have implemented strategies to improve diabetes care. Successful programs have published results showing improvement in important outcomes such as A1C measurements as well as process measures such as provision of eye exams. Features of successful programs reported in the literature include:

• Adoption of practice guidelines, with participation of the providers in the process. Guidelines should be readily accessible at the point of service, such as on patient charts, in examining rooms, or on office computer systems.

• Systems changes, such as provision of automated reminders to providers and patients, profiling or reporting of data to providers, and identification of patients at risk because of abnormal target values or a lack of reported values.

• Practice changes, such as scheduling of dedicated diabetes visits and group visits.

• Delivery of diabetes self-management education.

• Availability of case management services, usually by a nurse.

• Availability and involvement of expert consultants, such as endocrinologists and diabetes educators.

• Because these interventions are generally provided as components of a multifactorial intervention, it is difficult to assess the contribution of each component; however, it is clear that optimal diabetes management requires an organized, systematic approach and involvement of a health care team.

• Simple tools such as flow charts may be useful in smaller practices.