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, payers, and other interested persons 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 Skyler (Ed.): Medical Management of Type 1 Diabetes (1) and Zimmerman (Ed.): Medical Management of Type 2 Diabetes (2).

The recommendations included are 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 Association and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations

Classification

In 1997, the American Diabetes Association issued new diagnostic and classification criteria (3).

The classification of diabetes mellitus includes four clinical classes

  • Type 1 diabetes (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)

Diagnosis

Criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 2. Three ways to diagnosis diabetes are available and each must be confirmed on a subsequent day. Because of ease of use, acceptability to patients and lower cost, the fasting plasma glucose (FPG) is the preferred test.

Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is categorized as either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), depending on whether it is identified through a FPG or an oral glucose tolerance test (OGTT):   IFG = FPG ≥110 mg/dl (6.1 mmol/l) and  <126 mg/dl (7.0 mmol/l)  Or FPG 110 mg/dl (6.1 mmol/l)  to 125 mg/dl (6.9 mmol/l) IGT = 2-h PG ≥140 mg/dl (7.8 mmol/l)  and <200 mg/dl (11.1 mmol/l)  Or 2-h PG 140 mg/dl (7.8 mmol/l) to  199 mg/dl (11.0 mmol/l)  

Both categories, IFG and IGT, are risk factors for future diabetes and cardiovascular disease. Recent studies have shown that lifestyle interventions can reduce the rate of progression to type 2 diabetes (5,6,7).

Screening

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 of diabetes is well known, the natural history is well characterized, and there is good evidence for benefit from treating cases diagnosed through usual clinical care, there are no randomized trials demonstrating the benefits of early diagnosis through screening of asymptomatic individuals (8). 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 incidence of type 2 diabetes in children and adolescents has been shown to be increasing. 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 (9). See Table 4.

Detection and diagnosis of GDM

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 (10). A fasting plasma glucose ≥126 mg/dl or a casual plasma glucose ≥200 mg/dl meets the threshold for the diagnosis of diabetes, if confirmed on a subsequent day. 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 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 OGTT on that subset of women exceeding the glucose threshold value on the GCT. When the two-step approach is employed, 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 is as follows: ≥95 mg/dl fasting; ≥180 mg/dl at 1 h; ≥155 mg/dl at 2 h; ≥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

Recommendations

A-Level evidence

  • In those with IFG/IGT, lifestyle modification should be considered.

Expert consensus

  • The FPG is the preferred test to screen for and diagnose diabetes.

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

  • Screen for diabetes in pregnancy using risk factor analysis and screening tests as noted.

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. Elements of the initial medical evaluation are included in Table 5.

Management plan

People with diabetes should receive medical care from a physician-coordinated team. Such teams include, but are not limited to, physicians, nurses, dietitians, 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 or other medical conditions. Treatment goals must be set together with the patient, family, and health care team. Patient self-management should be emphasized, and the plan should emphasize the involvement of the patient in problem-solving as much as possible. A variety of strategies and techniques should be employed 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 be understood and agreed on by the patient and the care providers and that the goals and treatment plan are reasonable.

Glycemic control

Glycemic control is fundamental to the management of diabetes. Prospective randomized clinical trials have shown that achieving glycemic control is associated with decreased rates of retinopathy, nephropathy, and neuropathy, and epidemiological studies support the potential of intensive glycemic control in the reduction of cardiovascular disease.

In the Diabetes Control and Complications Trial (DCCT), 1,441 patients with type 1 diabetes were randomized to either standard or intensive care (11). The standard care group received one to two daily insulin injections and routine follow-up with treatment aimed at minimizing symptoms. Patients in the intensive care group were treated with multiple daily injections or continuous insulin infusion, received intensive diabetes self-management education, and were followed closely by a health care team with active case management that included monthly visits and weekly phone contact. The intensive treatment group achieved a mean HbA1c of ∼7% while the standard care group maintained an approximate HbA1c of 9%. With a mean of 6.5 years of follow-up, there were significant reductions in the incidence and rate of progression of retinopathy, albuminuria, and clinical neuropathy in the intensive group.

The U.K. Prospective Diabetes Study (UKPDS) enrolled newly diagnosed adults with type 2 diabetes (12,13). After 3 months of dietary treatment that reduced average HbA1c results from ∼9 to 7%, patients with FPG >6.0 mmol/l (107 mg/dl) were randomized to either intensive or standard treatment. In the intensive treatment group, patients were assigned to initial therapy with insulin, sulfonylurea, or metformin. In the standard care group, patients were maintained on lifestyle interventions until symptoms of marked hyperglycemia developed. Over time, both groups experi-enced deterioration in glycemic control.  A 0.9% difference in HbA1c values between the intensive and standard treatments groups (7 vs. 7.9%) was associated with significant reductions in all microvascular end points.

A recent systematic review examined cardiovascular outcomes in type 1 diabetes and included data from six randomized controlled trials comparing intensive insulin therapy versus conventional treatment (14). This review noted moderate treatment effects of glycemic control on macrovascular events. In the UKPDS, the trend toward a reduction in cardiovascular events did not reach statistical significance. However, epidemiological analysis of the UKPDS cohort showed a statistically significant effect of HbA1c lowering with an approximate 14% reduction in all-cause mortality and myocardial infarction for every 1% reduction in HbA1c (15). All of the above studies demonstrated an increased risk of hypoglycemia and weight gain associated with intensive glycemic control.

A major limitation to the available data is 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).

In summary, 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 has been found to increase risk of hypoglycemia and weight gain. Epidemiological analyses suggest that there is no threshold or lower limit of A1C above normal levels at which further lowering has no benefit. An average A1C >8% is associated with a higher risk of complications, at least in patients with reasonably long life expectancies. The relative benefit of achieving an A1C of 7% is documented in randomized controlled clinical trials with relative risk reductions of 15–30% per 1% absolute reduction in A1C.

Recommended glycemic goals for nonpregnant individuals are shown in Table 6 . 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. Postprandial glucose monitoring and therapies targeting postprandial excursions may be necessary to reach A1C goals and/or to reduce the risk of hypoglycemia. (16)

Elevated postchallenge (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of fasting plasma glucose in some epidemiological studies. Postprandial plasma glucose (PPG) levels >140 mg/dl are unusual in nondiabetic individuals, though 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 targets 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 average PPG values <180 mg/dl may lower A1C. However, it should be noted that this approach has not been validated to reduce complications in outcome studies in patients with either type 1 or type 2 diabetes.

For information on glycemic control for women with GDM, refer to the American Diabetes Association position statement on Gestational Diabetes Mellitus (10). For information on glycemic control during pregnancy in women with pre-existing diabetes, refer to Medical Management of Pregnancy Complicated by Diabetes (3rd ed.) (17).

Referral for diabetes management

For a variety of reasons (e.g., intercurrent illness, diabetic ketoacidosis [DKA], recurrent hypoglycemia), it may not be possible to provide care that achieves the desired goals of treatment (Table 6). In such instances, additional actions suggested may include enhanced diabetes self-management education, comanagement with a diabetes team, or referral to an endocrinologist if the patient is currently being followed by a primary care provider.

Intercurrent illness

The stress of illness frequently aggravates glycemic control and necessitates more frequent monitoring of blood glucose and urine or blood ketones. 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. A vomiting illness accompanied with ketosis may indicate DKA, a life-threatening condition that requires immediate medical care to prevent complications and death; the possibility of DKA should always be considered. (18)

Recommendations

A-Level evidence

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

B-Level evidence

  • Develop or adjust the management plan to achieve normal or near-normal glycemia with an A1C test goal of ≤7%.

  • Self-monitoring of blood glucose is an integral component of therapy

Expert consensus

  • 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.

Assessment of glycemic control

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

Self-monitoring of blood glucose

The American Diabetes Association’s consensus statements on self-monitoring of blood glucose (SMBG) provide a comprehensive review of the subject (19,20). As stated earlier, 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 if glycemic targets are being achieved. Results of SMBG are 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, 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.

Recommendations

Expert consensus

  • Include SMBG in the management plan.

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

A1C

By performing an A1C test, health providers can measure a patient’s average glycemia over the preceding 2–3 months 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, then as part of continuing care. Since the A1C test reflects a mean glycemia over the preceding 2–3 months, measurement approximately every 3 months is required to determine whether a patient’s metabolic control has reached and been maintained within the target range. Thus, regular performance of the A1C test permits detection of departures from the target range in a timely fashion. For any individual patient, the frequency of A1C testing should be dependent on the treatment regimen used and on the judgment of the clinician.

Recommendations

Expert consensus

  • 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.

MNT

MNT is an integral component of diabetes management and of diabetes self-management education. A review of the evidence and detailed information can be found in the American Diabetes Association technical review and position statement titled “Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications” (21,22).

Goals of MNT that apply to all persons with diabetes are as follows:

1) Attain and maintain optimal metabolic outcomes including

  • blood glucose levels in the normal range or as close to normal as is safely possible to prevent or reduce the risk for complications of diabetes

  • a lipid and lipoprotein profile that reduces the risk for macrovascular disease

  • blood pressure levels that reduce the risk for vascular disease

2) Prevent and treat the chronic complications of diabetes. Modify nutrient intake and lifestyle as appropriate for the prevention and treatment of obesity, dyslipidemia, cardiovascular disease, hypertension, and nephropathy.

3) Improve health through healthy food choices and physical activity

4) 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 medical nutrition therapy that apply to specific situations include the following:

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

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

3). For pregnant and lactating women, to provide adequate energy and nutrients needed for successful outcomes.

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

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

6) For individuals at risk for diabetes, to 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, changes must be made in the overall diabetes care and management plan.

Recommendations

B-Level evidence

  • 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 (19).

Physical activity

Association technical reviews on exercise in patients with diabetes have shown the value of exercise in the diabetes management plan (23,24). 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.

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.

Recommendations

B-Level evidence

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

Cardiovascular disease: management of risk factors and screening for CAD

Cardiovascular disease (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 American Diabetes Association technical reviews on hypertension (25), dyslipidemia (26), aspirin therapy (27), and smoking cessation (28) and in the consensus statement on CHD in people with diabetes (29). Emphasis should be placed on reducing cardiovascular risk factors, when possible, and clinicians should be alert for signs of atherosclerosis.

Blood pressure control

Hypertension (blood pressure ≥140/90 mmHg) is a common comorbidity of diabetes, affecting 20–60% of people with diabetes, depending on age, obesity, and ethnicity. Hypertension is also a major risk factor for cardiovascular disease 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 is likely to 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 incontrovertible benefit of lowering blood pressure to <140 mmHg systolic and <80 mmHg diastolic in persons with diabetes (30,31). Epidemiologic analyses show that blood pressures >120/80 mmHg are associated with increased cardiovascular event rates and mortality in persons with diabetes (32). 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, body weight (when indicated) and alcohol consumption and increasing activity levels have been shown to be effective in reducing blood pressure in nondiabetic individuals (33). These nonpharmacological strategies may also positively affect glycemia and lipid control.

Lowering of blood pressure with regimens based on antihypertensive drugs including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers, diuretics, and calcium channel blockers has been shown to be effective in lowering cardiovascular events and/or, in some studies, slowing progression of nephropathy and retinopathy. Other classes of hypertensive drugs have not been studied in diabetic patients with respect to improving outcomes. There is no conclusive evidence favoring one class of drugs, although several studies suggest that ACE inhibitors may be superior to dihydropyridine calcium channel blockers (DCCBs) in reducing cardiovascular events (34,35). ACE inhibitors have been shown to decrease the risk of progression of nephropathy in patients with type 1 diabetes and to decrease cardiovascular events in type 2 diabetic patients with or without hypertension. ARBs have been shown to reduce the rate of progression of nephropathy in patients with type 2 diabetes. The α-blocker arm of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was terminated after interim analysis showed that α-blockers were substantially less effective in reducing congestive heart failure than diuretic therapy (36). Many patients will require three or more drugs to reach target goals.

Before beginning treatment, patients with elevated blood pressures should have their blood pressure re-examined within 1 month to confirm the presence of hypertension unless the diastolic blood pressure is >110 mmHg. Patients with hypertension should be seen as often as needed until adequate blood pressure control is obtained and then seen as necessary; in these patients, other cardiovascular risk factors, including hyperlipidemia, smoking, urinary albumin excretion (assessed before initiation of treatment), and glycemic control, should be carefully assessed and treated.

Screening and Diagnosis

Expert consensus

  • 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.

  • Orthostatic measurement of blood pressure should be performed to assess for the presence of autonomic neuropathy.

Treatment

A-Level evidence

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

  • Patients with a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80–89 mmHg should be given lifestyle/behavioral therapy alone for a maximum of 3 months and then, if targets are not achieved, in addition, should be treated pharmacologically.

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

  • Initial drug therapy may be with ACE inhibitors, ARBs, β-blockers, or diuretics. Additonal drugs may be chosen from these classes or another drug class.

  • In hypertensive patients with microalbuminuria or clinical albuminuria/nephropathy, an ACE inhibitor or an ARB should be strongly considered. If one class is not tolerated, the other should be substituted.

  • In patients over age 55 years, with hypertension 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.

  • In patients with a recent myocardial infarction, β-blockers, in addition, should be considered to reduce mortality.

B-Level evidence

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

C-Level evidence

  • In patients with microalbuminuria or overt nephropathy, in whom ACE inhibitors or ARBs are not well tolerated, a non-DCCB should be considered.

Expert consensus

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

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

  • Patients not achieving target blood pressure on three drugs including a diuretic and patients with severe renal disease, should be referred to a specialist experienced in the care of patients with hypertension.

Lipid management

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 mellitus, particularly those who have had prior cardiovascular events.

In three secondary prevention studies using HMG CoA reductase inhibitors (statins), patients with diabetes achieved significant reductions in coronary and cerebrovascular events (37,38,39). A primary prevention study using statins showed a similar trend of reduced events in the small number of patients with diabetes (40). In two studies using the fibric acid derivative gemfibrozil, reductions in cardiovascular end points were also achieved (41,42). In the Helsinki Heart Study, a primary prevention trial, a trend toward significant reductions in CHD events was observed in the small group of subjects with diabetes mellitus (41). In the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), a secondary trial, a significant reduction in events occurred with improved HDL and triglycerides and no change in LDL cholesterol. (42)

Target lipid levels are shown in Table 7. Nutrition assessment and intervention, increased physical activity, and weight loss 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 and cholesterol intake. Glycemic control can also beneficially modify plasma lipid levels. In particular, triglycerides may be significantly reduced with optimal glucose lowering.

Pharmacological treatment is indicated if there is an inadequate response to lifestyle modifications and improved glucose control. 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. Statins raise HDL modestly, but a greater increase is usually achieved with fibrates.

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 and pharmacological treatment with a statin. In addition, if the HDL is <40 mg/dl and the LDL is between 100 and 129 mg/dl, a fibric acid such as fenofibrate might be used.

Niacin is the best drug for raising HDL but may significantly increase blood glucose (43). However, glycemic control may be maintained with appropriate adjustment of diabetes therapy and moderate does of nicotinic acid (≤3 g/day).

Combination therapy, with a statin and a fibrate, may be efficacious for patients needing treatment for all three lipid fractions, but this combination is associated with an increased risk for myositis and/or rhabdomyolysis.

Following the recommendations of the National Cholesterol Education Program’s Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents, LDL cholesterol should be lowered to ≤110 mg/dl (2.80 mmol/l) in children with cardiovascular risk factors in addition to diabetes (44).

General recommendations

A-Level evidence

  • Lowering LDL cholesterol is associated with a reduction in cardiovascular events.

B-Level evidence

  • Lowering triglycerides and increasing HDL cholesterol are associated with a reduction in cardiovascular events.

Goals

B-Level evidence

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

C-Level evidence

  • Lower triglycerides to <150 mg/dl (1.7 mmol/l) and raise HDL cholesterol to >45 mg/dl (1.15 mmol/l) in men and >55 mg/dl (1.40 mmol/l) in women.

Screening

Expert consensus

  • 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 (Table 6), repeat lipid assessments every 2 years.

  • In children >2 years of age, perform a lipid profile after diagnosis of diabetes and when glucose control has been established. If values are considered low risk and there is no family history, assessments should be repeated every 5 years.

Treatment

A-Level evidence

  • MNT focusing on the reduction of saturated fat and cholesterol intake, weight loss, and increased physical activity has been shown to improve the lipid profile in patients with diabetes.

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

  • Statins should be used as first-line pharmacologic therapy for LDL lowering.

  • Therapy with fibrates in patients with low HDL has been shown to reduce CVD rates and progression of carotid intimal medial progression. When prescribing fibrates, in combination therapy with a statin, care is needed to minimize the risk of myositis.

Aspirin therapy in diabetes

Aspirin blocks thromboxane synthesis by acetylating platelet cyclo-oxygenase and has been used as a primary 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 approximate 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 cardiovascular disease, males and females, and patients with hypertension.

Dosages used in most clinical trials ranged from 75–325 mg/day. There is no evidence to support any specific dose, but using the lowest possible dosage and enteric-coated preparations may help reduce side effects.

There is no evidence for a specific age at which to start aspirin, but at ages below 30 years, when the risk of CVD is low, there is no evidence of benefit of aspirin for primary prevention.

In a secondary analysis of some studies, aspirin therapy may have lessened the beneficial effects of ACE inhibitors in patients with established CVD (i.e., prior myocardial infarction, angina, and congestive heart failure) (46). However, pending additional studies, therapy with ACE inhibitors does not preclude the use of aspirin. Clopidogrel has been demonstarted to reduce CVD rates in nondiabetic individuals. Adjunctive therapy in very high–risk patients or as alternative therapy in aspirin-intolerant patients should be considered.

Recommendation

A-Level evidence

  • Use aspirin therapy (75–325 mg/day) in all adult patients with diabetes and macrovascular disease.

  • Consider beginning aspirin therapy (75–325 mg/day) for primary prevention in patients ≥40 years of age with diabetes and one or more other cardiovascular risk factors.

  • Do not use aspirin in patients <21 years of age because of the increased risk of Reye’s syndrome.

B-Level evidence

  • Consider aspirin therapy for patients between 30 and 40 years of age with other cardiovascular risk factors.

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 (28). Cigarette smoking accounts for 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 discuss separately results on subsets of individuals with diabetes, suggesting 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 the others specific to individuals with diabetes, suggest that smoking cessation counseling is effective in reducing tobacco use (47,48).

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.

Recommendations

A-Level evidence

  • Advise all patients not to smoke.

B-Level evidence

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

CHD screening and treatment

To identify the presence of CHD in diabetic patients without clear or suggestive symptoms of 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 macroalbumuninuria. Candidates for screening exercise stress (ECG) testing include those with 1) typical or atypical cardiac symptoms; 2) an abnormal resting ECG; 3) a history of peripheral or carotid occlusive disease; 4) sedentary lifestyle, age >35 years, and plans to begin a vigorous exercise program; or 5) those with two or more risk factors noted above. There is, however, no current evidence that exercise testing in asymptomatic patients with risk factors improves prognosis. Patients with abnormal exercise ECG and patients unable to perform an exercise ECG require additional/alternative testing. Currently, stress nuclear perfusion and stress ECHO are valuable next-level diagnostic procedures. A consultation with a cardiologist is recommended regarding further work-up (29).

Recommendations

Expert consensus

  • 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 ECHO and/or perfusion imaging.

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

Nephropathy screening and treatment

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 and is also a significant marker for CVD. Patients with microalbuminuria likely progress to clinical albuminuria (≥300 mg/24 h) and decreasing glomerular filtration rate (GFR) over a period of years. Once clinical albuminuria occurs, the risk for ESRD is high in type 1 diabetes and significant in type 2 diabetes.

Over the past several years, a number of interventions have been demonstrated to reduce the risk and to 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 microalbuminuria to clinical albuminuria in patients with type 1 (49,50) and type 2 diabetes (12). The UKPDS conclusively proved that hypertension control can slow the progression of nephropathy (31). In addition, large prospective randomized studies in patients with type 1 and type 2 diabetes have demonstrated that treatment with ACE inhibitors and ARBs provides a selective benefit over other antihypertensive agents in delaying the progression from microalbuminuria to clinical albuminuria and can slow the decline in GFR in patients with clinical albuminuria (51,52,53,54,55). In addition, ACE inhibitors have been shown to reduce severe cardiovascular disease (i.e., myocardial infarction, stroke, death), thus further supporting the use of these agents in patients with microalbuminuria (55). ARBs have also been shown to reduce the rate of progression of albuminuria and clinical nephropathy in patients with type 2 diabetes (56,57,58).

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 (59).

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

The role of annual urine protein dipstick testing and microalbumuria assessment is less clear after diagnosis of microalbuminuria and institution of ACE inhibitor or ARB therapy and blood pressure control. Many experts recommend continued surveillance both to assess response to therapy and progression of disease.

For a complete discussion on the treatment of nephropathy, see the American Diabetes Association’s position statement “Diabetic Nephropathy” (60).

General recommendations

A-Level evidence

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

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

Screening

Expert consensus

  • Perform an annual test for the presence of microalbuminia in 1) type 1 diabetic patients who have had diabetes >5 years and 2) all type 2 diabetic patients starting at diagnosis.

Treatment

A-Level evidence

  • In the treatment of albuminuria/nephropathy, both ACE inhibitors and ARBs can be used:

  • in hypertensive and nonhypertensive type 1 diabetic patients with microalbuminuria or clinical albuminuria, ACE inhibitors are the initial agents of choice;

  • in hypertensive type 2 diabetic patients with microalbuminuria or clinical albuminuria, ARBs are the initial agents of choice.

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

B-Level evidence

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

  • Combination of ACE inhibitors and ARBs will decrease albuminuria more than with either agent alone.

Expert consensus

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

  • Consider referral to a physician experienced in the care of diabetic renal disease when the GFR has fallen to either <70 ml · min−1 · 1.73 m−2, serum creatinine has increased to >2.0 mg/dl (>180 μmol/l), or difficulties occur in the management of hypertension or hyperkalemia.

  • Consider the use of non-DCCBs in patients unable to tolerate ACE inhibitors or ARBs.

Foot care

Amputation and foot ulceration are one of the most common consequences of diabetic neuropathy and a major cause 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

Targeted patient education and appropriate footwear can reduce the risk of ulceration. For a detailed review of the evidence and further discussion, see the American Diabetes Association’s technical review and position statement titled “Preventive Foot Care in Persons With Diabetes” (61,62).

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 American Diabetes Association’s consensus statement on diabetic foot wound care (63).

Recommendations

A-Level evidence

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

B-Level evidence

  • 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.

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

C-Level evidence

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

  • Refer patients with claudication for further vascular assessment and consider exercise and surgical options.

Expert consensus

  • 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.

Diabetic retinopathy screening and treatment

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 (11,12). 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 shown in 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 (64). During pregnancy and 1 year postpartum, retinopathy may be transiently aggravated; laser surgery can minimize this risk (65).

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) (66,67,68,69,70) and the Early Treatment Diabetic Retinopathy Study (ETDRS), provide the strongest support for the therapeutic benefit of photocoagulation surgery (71,72,73,74,75,76,77).

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 eyes 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 American Diabetes Association’s technical review and position statement on this subject (64,78).

General Recommendations

A-Level evidence

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

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

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

Screening

B-Level evidence

  • 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 is made.

  • 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. Examinations will be required more frequently if retinopathy is progressing.

  • When planning pregnancy, women with pre-existing 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.

Treatment

A-Level evidence

  • Laser therapy can reduce the risk of vision loss in patients with high-risk characteristics.

  • 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.

Preconception Care

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 indexed by first trimester A1C concentrations. There is no threshhold 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.

Five nonrandomized studies have compared rates of major malformations in the 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 self-monitoring of blood glucose. Goals were set to achieve normal blood glucose concentrations, and >80% of subjects achieved normal A1C concentrations before they became pregnant (79,80,81,82,83). 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 preconceptional 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, internist or 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 American Diabetes Association’s technical review and position statement on this subject (84,85).

Recommendations

B-Level evidence

  • A1C levels should be normal or as close to normal as possible in an individual patient before conception is attempted.

C-Level evidence

  • ACE inhibitors should be discontinued before pregnancy.

Expert consensus

  • 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.

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

  • Oral antidiabetic agents and ARBs should be discontinued before pregnancy.

Immunization

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 (86). 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 which can greatly reduce the risk of serious complications from these diseases (87,88). There is sufficient evidence to support that people with diabetes have appropriate seriologic 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 (89,90).

Recommendations

C-Level evidence

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

  • 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 more than 5 years ago. Other indications for repeat vaccination include nephrotic syndrome, chronic renal disease, and other immunocompromised states, such as postorgan transplantation.

Care of older adults with diabetes

Diabetes is an important health condition for the aging population; ∼10% 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. Unfortunately, there are no long-term studies demonstrating the benefits of tight glycemic control in persons over 65 years of age. In approaching the elderly patient, a thoughtful individualized approach, consistent with the heterogeneity of the aging process, should be used. However, patients who can be expected to live long enough to reap the benefits of long-term glycemic control (10–20 years) and who are active, cognitively intact, and willing to undertake the responsibility of self management should be encouraged to do so.

For patients with advanced diabetes complications, life-limiting comorbid illness, or cognitive or functional impairment, it is reasonable to set higher target goals. These patients are less likely to benefit from reducing microvascular complications and more likely to suffer serious adverse effects from hypoglycemia. Chronic hyperglycemia can cause a catabolic state leading to malnutrition, functional impairment, and symptom with decreased quality of life. Also, patients with poorly controlled diabetes may be subject to acute complications of diabetes, including hyperglycemic hyperosmolar coma. Reasonable targets, not based on evidence, would be a fasting glucose <140 mg/dl and postprandial glucose <200–220 mg/dl.

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 secretogogues can cause hypoglycemia. Insulin can also cause hypoglycemia as well as requiring 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 (NYHA Class III and IV). α-Glucosidase inhibitors are safe but may not be well tolerated and may not be effective as monotherapy. Drugs should be started at the lowest dose and titrated up gradually until targets are reached or side effects develop.

Cardiovascular risk reduction continues to be important as in younger patients; 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 diabetes patients have such an elevated risk for CVD that aggressive management of lipids and aspirin use when not contraindicated are probably reasonable interventions.

Children and adolescents

Approximately three-quarters of all newly diagnosed cases of type 1 diabetes occur in individuals younger than 18 years. 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 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 (18). 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 diabetic regimen. For example, an adolescent who requires more flexibility might be switched to a three– or four–insulin injection program 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. 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. Although there are insufficient data to make definite recommendations, a recent American Diabetes Association 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. Many patients can be managed initially with MNT and exercise, but most will eventually require drug therapy. Successful control of comorbidities, such as hypertension and hyperlipidemia, is also important. For further discussion, see the American Diabetes Association consensus statement “Type 2 Diabetes in Children and Adolescents” (9).

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.

For further discussion, see the American Diabetes Association’s position statement “The Care of Children With Diabetes in the School and Day Care Setting” (91).

Strategies for successful guideline implementation

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.

Table 1—

ADA evidence grading system for clinical practice recommendations

Level of evidenceDescription
Clear evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered including: 
 • Evidence from a well-conducted multicenter trial 
 • Evidence from a meta-analysis that incorporated quality ratings in the analysis. 
 • Compelling nonexperimental evidence, i.e., “all or none” rule developed by Center for Evidence Based Medicine at Oxford* 
 Supportive evidence from well-conducted randomized controlled trials that are adequately powered including: 
 • Evidence from a well-conducted trial at one or more institutions 
 • Evidence from a meta-analysis that incorporated quality ratings in the analysis 
Supportive evidence from well-conducted cohort studies 
 • Evidence from a well-conducted prospective cohort study or registry 
 • Evidence from a well-conducted prospective cohort study 
 • Evidence from a well-conducted meta-analysis of cohort studies 
 Supportive evidence from well-conducted case-control study 
Supportive evidence from poorly controlled or uncontrolled studies 
 • Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results 
 • Evidence from observational studies with high potential for bias (such as case series with comparison to historical controls) 
 • Evidence from case series or case reports 
 Conflicting evidence with the weight of evidence supporting the recommendation 
Expert consensus or clinical experience 
Level of evidenceDescription
Clear evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered including: 
 • Evidence from a well-conducted multicenter trial 
 • Evidence from a meta-analysis that incorporated quality ratings in the analysis. 
 • Compelling nonexperimental evidence, i.e., “all or none” rule developed by Center for Evidence Based Medicine at Oxford* 
 Supportive evidence from well-conducted randomized controlled trials that are adequately powered including: 
 • Evidence from a well-conducted trial at one or more institutions 
 • Evidence from a meta-analysis that incorporated quality ratings in the analysis 
Supportive evidence from well-conducted cohort studies 
 • Evidence from a well-conducted prospective cohort study or registry 
 • Evidence from a well-conducted prospective cohort study 
 • Evidence from a well-conducted meta-analysis of cohort studies 
 Supportive evidence from well-conducted case-control study 
Supportive evidence from poorly controlled or uncontrolled studies 
 • Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results 
 • Evidence from observational studies with high potential for bias (such as case series with comparison to historical controls) 
 • Evidence from case series or case reports 
 Conflicting evidence with the weight of evidence supporting the recommendation 
Expert consensus or clinical experience 
*

Either all patients died prior to therapy and at least some survived with therapy, or some patients died without therapy and none died with therapy. Example: use of insulin in the treatment of DKA.

Table 2—

Criteria for the diagnosis of diabetes*

1. Symptoms of diabetes and a casual plasma glucose ≥200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. 
OR 
2. FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h. 
OR 
3. 2-h PG ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization (4), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. 
1. Symptoms of diabetes and a casual plasma glucose ≥200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. 
OR 
2. FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h. 
OR 
3. 2-h PG ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization (4), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. 
*

In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day. The OGTT is not recommended for routine clinical use, but may be required in the evaluation of patients with IFG (see text) or when diabetes is still suspected despite a normal FPG.

Table 3—

Criteria for testing for diabetes in asymptomatic adult individuals

1. Testing for diabetes should be considered in all individuals at age 45 years and above  and, if normal, it should be repeated at 3-year intervals. 
2. Testing should be considered at a younger age or be carried out more frequently in  individuals who • are overweight (BMI ≥25 kg/m2) • have a first-degree relative with diabetes • are members of a high-risk ethnic population (e.g., African-American, Latino, Native  American, Asian-American, Pacific Islander) • have delivered a baby weighing >9 lb or have been diagnosed with GDM • are hypertensive (≥140/90 mmHg) • have an HDL cholesterol level ≤35 mg/dl (0.90 mmol/l) and/or a triglyceride level  ≥250 mg/dl (2.82 mmol/l) • on previous testing, had IGT or IFG • have other clinical conditions associated with insulin resistance (e.g. PCOS or  acanthosis nigricans) 
1. Testing for diabetes should be considered in all individuals at age 45 years and above  and, if normal, it should be repeated at 3-year intervals. 
2. Testing should be considered at a younger age or be carried out more frequently in  individuals who • are overweight (BMI ≥25 kg/m2) • have a first-degree relative with diabetes • are members of a high-risk ethnic population (e.g., African-American, Latino, Native  American, Asian-American, Pacific Islander) • have delivered a baby weighing >9 lb or have been diagnosed with GDM • are hypertensive (≥140/90 mmHg) • have an HDL cholesterol level ≤35 mg/dl (0.90 mmol/l) and/or a triglyceride level  ≥250 mg/dl (2.82 mmol/l) • on previous testing, had IGT or IFG • have other clinical conditions associated with insulin resistance (e.g. PCOS or  acanthosis nigricans) 
Table 4—

Testing for type 2 diabetes in children

• Criteria* 
 Overweight (BMI >85th percentile for age and sex, weight for height >85th percentile, or  weight >120% of ideal for height) 
Plus 
 Any two of the following risk factors: 
  Family history of type 2 diabetes in first- or second-degree relative 
  Race/ethnicity (Native American, African-American, Latino, Asian-American, Pacific   Islander) 
  Signs of insulin resistance or conditions associated with insulin resistance (acanthosis   nigricans, hypertension, dyslipidemia, or PCOS) 
• Age of initiation: age 10 years or at onset of puberty, if puberty occurs at a younger age 
• Frequency: every 2 years 
• Test: FPG preferred 
• Criteria* 
 Overweight (BMI >85th percentile for age and sex, weight for height >85th percentile, or  weight >120% of ideal for height) 
Plus 
 Any two of the following risk factors: 
  Family history of type 2 diabetes in first- or second-degree relative 
  Race/ethnicity (Native American, African-American, Latino, Asian-American, Pacific   Islander) 
  Signs of insulin resistance or conditions associated with insulin resistance (acanthosis   nigricans, hypertension, dyslipidemia, or PCOS) 
• Age of initiation: age 10 years or at onset of puberty, if puberty occurs at a younger age 
• Frequency: every 2 years 
• Test: FPG preferred 
*

Clinical judgment should be used to test for diabetes in high-risk patients who do not meet these criteria.

Table 5—

Components of the initial visit

Medical history 
• Symptoms, results of laboratory tests, and special examination results related to the diagnosis of diabetes 
• Prior A1C records 
• Eating patterns, nutritional status, and weight history; growth and development in children and adolescents 
• Details of previous treatment programs, including nutrition and diabetes self-management education, attitudes, and health beliefs 
• Current treatment of diabetes, including medications, meal plan, and results of glucose monitoring and patients’ use of data 
• Exercise history 
• Frequency, severity, and cause of acute complications such as ketoacidosis and hypoglycemia 
• Prior or current infections, particularly skin, foot, dental, and genitourinary infections 
• Symptoms and treatment of chronic eye; kidney; nerve; genitourinary (including sexual), bladder, and gastrointestinal function (including symptoms of celiac disease in type 1 diabetic patients); heart; peripheral vascular; foot; and cerebrovascular complications associated with diabetes 
• Other medications that may affect blood glucose levels 
• Risk factors for atherosclerosis: smoking, hypertension, obesity, dyslipidemia, and family history 
• History and treatment of other conditions, including endocrine and eating disorders 
• Family history of diabetes and other endocrine disorders 
• Lifestyle, cultural, psychosocial, educational, and economic factors that might influence the management of diabetes 
• Tobacco, alcohol and/or controlled substance use 
• Contraception and reproductive and sexual history 
Physical examination 
• Height and weight measurement (and comparison to norms in children and adolescents) 
• Sexual maturation staging (during pubertal period) 
• Blood pressure determination, including orthostatic measurements when indicated, and comparison to age-related norms 
• Fundoscopic examination 
• Oral examination 
• Thyroid palpation 
• Cardiac examination 
• Abdominal examination (e.g., for hepatomegaly) 
• Evaluation of pulses by palpation and with auscultation 
• Hand/finger examination 
• Foot examination 
• Skin examination (for acanthosis nigricans and insulin-injection sites) 
• Neurological examination 
• Signs of diseases that can cause secondary diabetes (e.g., hemochromatosis, pancreatic disease) 
Laboratory evaluation 
• A1C 
• Fasting lipid profile, including total cholesterol, HDL cholesterol, triglycerides, and LDL cholesterol 
• Test for microalbuminuria in type 1 diabetic patients who have had diabetes for at least 5 years and in all patients with type 2 diabetes. Some advocate beginning screening of pubertal children before 5 years of diabetes. 
• Serum creatinine in adults (in children if proteinuria is present) 
• Thyroid-stimulating hormone (TSH) in all type 1 diabetic patients; in type 2 if clinically indicated 
• Electrocardiogram in adults 
• Urinalysis for ketones, protein, sediment 
Referrals 
• Eye exam, if indicated 
• Family planning for women of reproductive age 
• MNT, as indicated 
• Diabetes educator, if not provided by physician or practice staff 
• Behavioral specialist, as indicated 
• Foot specialist, as indicated 
• Other specialties and services as appropriate 
Medical history 
• Symptoms, results of laboratory tests, and special examination results related to the diagnosis of diabetes 
• Prior A1C records 
• Eating patterns, nutritional status, and weight history; growth and development in children and adolescents 
• Details of previous treatment programs, including nutrition and diabetes self-management education, attitudes, and health beliefs 
• Current treatment of diabetes, including medications, meal plan, and results of glucose monitoring and patients’ use of data 
• Exercise history 
• Frequency, severity, and cause of acute complications such as ketoacidosis and hypoglycemia 
• Prior or current infections, particularly skin, foot, dental, and genitourinary infections 
• Symptoms and treatment of chronic eye; kidney; nerve; genitourinary (including sexual), bladder, and gastrointestinal function (including symptoms of celiac disease in type 1 diabetic patients); heart; peripheral vascular; foot; and cerebrovascular complications associated with diabetes 
• Other medications that may affect blood glucose levels 
• Risk factors for atherosclerosis: smoking, hypertension, obesity, dyslipidemia, and family history 
• History and treatment of other conditions, including endocrine and eating disorders 
• Family history of diabetes and other endocrine disorders 
• Lifestyle, cultural, psychosocial, educational, and economic factors that might influence the management of diabetes 
• Tobacco, alcohol and/or controlled substance use 
• Contraception and reproductive and sexual history 
Physical examination 
• Height and weight measurement (and comparison to norms in children and adolescents) 
• Sexual maturation staging (during pubertal period) 
• Blood pressure determination, including orthostatic measurements when indicated, and comparison to age-related norms 
• Fundoscopic examination 
• Oral examination 
• Thyroid palpation 
• Cardiac examination 
• Abdominal examination (e.g., for hepatomegaly) 
• Evaluation of pulses by palpation and with auscultation 
• Hand/finger examination 
• Foot examination 
• Skin examination (for acanthosis nigricans and insulin-injection sites) 
• Neurological examination 
• Signs of diseases that can cause secondary diabetes (e.g., hemochromatosis, pancreatic disease) 
Laboratory evaluation 
• A1C 
• Fasting lipid profile, including total cholesterol, HDL cholesterol, triglycerides, and LDL cholesterol 
• Test for microalbuminuria in type 1 diabetic patients who have had diabetes for at least 5 years and in all patients with type 2 diabetes. Some advocate beginning screening of pubertal children before 5 years of diabetes. 
• Serum creatinine in adults (in children if proteinuria is present) 
• Thyroid-stimulating hormone (TSH) in all type 1 diabetic patients; in type 2 if clinically indicated 
• Electrocardiogram in adults 
• Urinalysis for ketones, protein, sediment 
Referrals 
• Eye exam, if indicated 
• Family planning for women of reproductive age 
• MNT, as indicated 
• Diabetes educator, if not provided by physician or practice staff 
• Behavioral specialist, as indicated 
• Foot specialist, as indicated 
• Other specialties and services as appropriate 
Table 6—

Glycemic control for nonpregnant individuals with diabetes

NormalGoalAdditional action suggested*
Plasma values    
 Average preprandial glucose (mg/dl) <110 90–130 <90/>150 
 Average bedtime glucose (mg/dl) <120 110–150 <110/>180 
Whole blood values    
 Average preprandial glucose (mg/dl) <100 80–120 <80/>140 
 Average bedtime glucose (mg/dl) <110 100–140 <100/>160 
A1C (%) <6 <7 >8 
NormalGoalAdditional action suggested*
Plasma values    
 Average preprandial glucose (mg/dl) <110 90–130 <90/>150 
 Average bedtime glucose (mg/dl) <120 110–150 <110/>180 
Whole blood values    
 Average preprandial glucose (mg/dl) <100 80–120 <80/>140 
 Average bedtime glucose (mg/dl) <110 100–140 <100/>160 
A1C (%) <6 <7 >8 

The values shown in this table are by necessity generalized to the entire population of individuals with diabetes. Patients with comorbid diseases, the very young and older adults, and others with unusual conditions or circumstances may warrant different treatment goals. These values are for nonpregnant adults.

*

Values above/below these levels are not “goals” nor are they “acceptable” in most patients. They are an indication for a significant change in the treatment plan. “Additional action suggested” depends on individual patient circumstances. Such actions may include enhanced diabetes self-management education, comanagement with a diabetes team, referral to an endocrinologist, change in pharmacological therapy, initiation of or increase in SMBG, or more frequent contact with the patient. A1C is referenced to a nondiabetic range of 4.0–6.0% (mean 5.0%, SD 0.5%).

Values callibrated to plasma glucose,

measurement of capillary blood glucose.

Table 7—

Target lipid levels for adult patients with diabetes

GoalLevel of evidence
LDL cholesterol <100 mg/dl (2.6 mmol/l) 
HDL cholesterol Men: >45 mg/dl (1.15 mmol/l) 
 Women: >55 mg/dl (1.40 mmol/l)  
Triglycerides <150 mg/dl (1.7 mmol/l) 
GoalLevel of evidence
LDL cholesterol <100 mg/dl (2.6 mmol/l) 
HDL cholesterol Men: >45 mg/dl (1.15 mmol/l) 
 Women: >55 mg/dl (1.40 mmol/l)  
Triglycerides <150 mg/dl (1.7 mmol/l) 

Note: The recent NCEP/ATP III guidelines suggest that in patients with triglycerides ≥200 mg/dl, the “non-HDL cholesterol” be calculated with a goal being <130 (45).

Table 8—

Definitions of abnormalities in albumin excretion

Category24-h collection (mg/24 h)Timed collection (μg/min)Spot collection (μg/mg creatinine)
Normal <30 <20 <30 
Microalbuminuria 30–299 20–199 30–299 
Clinical albuminuria ≥300 ≥200 ≥300 
Category24-h collection (mg/24 h)Timed collection (μg/min)Spot collection (μg/mg creatinine)
Normal <30 <20 <30 
Microalbuminuria 30–299 20–199 30–299 
Clinical albuminuria ≥300 ≥200 ≥300 

Because of variability in urinary albumin excretion, two of three specimens collected within a 3- to 6-month period should be abnormal before considering a patient to have crossed one of these diagnostic thresholds. Exercise within 24 h, infection, fever, congestive heart failure, marked hyperglycemia, and marked hypertension may elevate urinary albumin excretion over baseline values.

1.
Skyler JS (Ed.): Medical Management of Type 1 Diabetes. 3rd ed. Alexandria, VA, American Diabetes Association, 1998
2.
Zimmerman BR (Ed.): Medical Management of Type 2 Diabetes. 4th ed. Alexandria, VA, American Diabetes Association, 1998
3.
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care
25(Suppl. 1)
:
S5
–S20,
2002
4.
World Health Organization: Diabetes Mellitus: Report of a WHO Study Group. Geneva, World Health Org., 1985 (Tech. Rep. Ser., no.727)
5.
Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaaniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M: Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
N Engl J Med
344
:
1343
–1350,
2001
6.
Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV: Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The DaQing IGT and Diabetes Study.
Diabetes Care
20
:
537
–544,
1997
7.
Available on the internet. www.preventdiabetes.com. Accessed October 2001
8.
Engelgau ME, Narayan KMV, Herman WH: Screening for type 2 diabetes (Technical Review).
Diabetes Care
10
:
1563
–1580,
2000
9.
American Diabetes Association: Type 2 diabetes in children and adolescents (Consensus Statement).
Diabetes Care
23
:
381
–389,
2000
10.
American Diabetes Association: Gestational diabetes mellitus (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S94
–S96,
2002
11.
Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med
329
:
977
–986,
1993
12.
UK Prospective Diabetes Study Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
Lancet
352
:
837
–853,
1998
13.
UK Prospective Diabetes Study Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34).
Lancet
352
:
854
–865,
1998
14.
Lawson ML, Gerstein HC, Tsui E, Zinman B: Effect of intensive therapy on early macrovascular disease in young individuals with type 1 diabetes.
Diabetes Care
22(Suppl. 1)
:
B35
–B39,
1999
15.
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
BMJ
321
:
405
–412,
2000
16.
American Diabetes Association: Postprandial blood glucose (Consensus Statement).
Diabetes Care
24
:
775
–778,
2001
17.
Jovanovic L (Ed.): Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, VA, American Diabetes Association, 2000
18.
American Diabetes Association: Management of hyperglycemic crises in patients with diabetes (Position Statement).
Diabetes Care
25 (Suppl. 1): S100–S108, 2002
19.
American Diabetes Association: Self-monitoring of blood glucose (Consensus Statement).
Diabetes Care
17
:
81
–86,
1994
20.
American Diabetes Association: Self-monitoring of blood glucose (Consensus Statement).
Diabetes Care
10
:
93
–99,
1987
21.
Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson JL, Garg A, Holzmeister L, Hoogwerf BJ, Mayer-Davis E, Mooradian AD, Purnell JQ, Wheeler M: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications (Technical Review).
Diabetes Care
25: 148–198, 2002
22.
American Diabetes Association: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S50
-S60, 2002
23.
Schneider SH, Ruderman NB: Exercise and NIDDM (Technical Review).
Diabetes Care
13
:
785
–789,
1990
24.
Wasserman DH, Zinman B: Exercise in individuals with IDDM (Technical Review).
Diabetes Care
17
:
924
–937,
1994
25.
Arauz-Pacheco C, Parrott MA, Raskin P: The treatment of hypertension in adult patients with diabetes mellitus (Technical Review).
Diabetes Care
25
:
134
–147,
2002
26.
Haffner SM: Management of dyslipidemia in adults with diabetes (Technical Review).
Diabetes Care
21
:
160
–178,
1998
27.
Colwell JA: Aspirin therapy in diabetes (Technical Review).
Diabetes Care
20
:
1767
–1771,
1997
28.
Haire-Joshu D, Glasgow RE, Tibbs TL: Smoking and diabetes (Technical Review).
Diabetes Care
22
:
1887
–1898,
1999
29.
American Diabetes Association: Consensus development conference on the diagnosis of coronary heart disease in people with diabetes (Consensus Statement).
Diabetes Care
21
:
1551
–1559,
1998
30.
Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI).
Arch Int Med
157
:
2413
–2446,
1997
31.
UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.
BMJ
317
:
703
–713,
1998
32.
Hansson L, Zanchett A, Carruthers SG, et al: Effects of intensive blood-pressure lowering and low-dose aspirin on patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial.
Lancet
351
:
1755
–1762,
1998
33.
Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N: A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
N Engl J Med
336
:
1117
–1124,
1997
34.
Tatti P, Paahron M, Byington RP, Di Mauro P, Guarisco R, Strollo G, Strollo F: Outcome results of Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM.
Diabetes Care
21
:
597
–603,
1998
35.
Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW: The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.
N Engl J Med
338
:
645
–654,
1998
36.
Messerli FH: Implications of discontinuation of doxazosin arm of ALLHAT. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
Lancet
355
:
863
–864,
2000
37.
Pyorala K, Pedersen TR, Kjeksus J, Faergeman O, Olsson AG, Thorgeirsson G: Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Study (4S).
Diabetes Care
20
:
614
–620,
1997
38.
Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E, for the Cholesterol and Recurrent Events Trial Investigators: The effect of pravastatin on coronary events after myocardial infarction I patients with average cholesterol levels: Cholesterol and Recurrent Events Trial Investigators.
N Engl J Med
335
:
1001
–1009,
1996
39.
Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.
N Engl J Med
339
:
1349
–1357,
1998
40.
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study JAMA
279
:
1615
–1622,
1998
41.
Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.
N Engl J Med
317
:
1237
–1245,
1987
42.
Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.
N Engl J Med
341
:
410
–418,
1999
43.
Elam MB, Hunninghake DB, Davis KB, Garg R, Johnson C, Egan D, Kostis JB, Sheps DS, Brinton EA: Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease.
JAMA
284: 1263–1270, 2000
44.
Expert Panel on Blood Cholesterol Levels in Children and Adolescents: Treatment recommendations of the National Cholesterol Education Program Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents.
Pediatrics
89 (Suppl.):525–584, 1992
45.
The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
JAMA
285
:
2486
–2497,
2001
46.
Peterson JG, Topol EJ, Sapp SK, Young JB, Lincoff AM, Lauer MS: Evaluation of the effects of aspirin combined with angiotensin-converting enzyme inhibitors in patients with coronary artery disease.
Am J Med
109
:
371
–377,
2000
47.
U.S: Preventive Services Task Force: Counseling to prevent tobacco use. In Guide to Clinical Preventive Services. 2nd ed. Baltimore, MD, Williams & Wilkins, 1996, p. 597–609
48.
Fiore M, Bailey W, Cohen S: Smoking Cessation: Clinical Practice Guideline Number 18. Rockville, MD, U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996
49.
Reichard P, Nilsson B-Y, Rosenqvist U: The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus.
N Engl J Med
329
:
304
–309,
1993
50.
The DCCT Research Group: Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial (DCCT).
Kidney Int
47
:
1703
–1720,
1995
51.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD for the Collaborative Study Group: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.
N Engl J Med
329
:
1456
–1462,
1993
52.
Laffel LMB, McGill JB, Gans DJ, and the North American Microalbuminuria Study Group (NAMSG): The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria.
Am J Med
99
:
497
–504,
1995
53.
Ravid M, Brosh D, Levi Z, Bar-Dayan Y, Ravid D, Rachmani R: Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus.
Ann Intern Med
128
:
982
–988,
1998
54.
Ravid M, Lang R, Rachmani R, Lishner M: Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.
Arch Intern Med
156
:
286
–289,
1996
55.
Heart Outcomes Prevention Evaluation (HOPE) Study Investigators: Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE study.
Lancet
355
:
253
–259,
2000
56.
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
N Engl J Med
345
:
851
–860,
2001
57.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
N Engl J Med
345
:
861
–869,
2001
58.
Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.
N Engl J Med
345
:
870
–878,
2001
59.
Anderson S, Tarnow L, Rossing P, Hansen BV, Parving HH: Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy.
Kidney Int
57
:
601
–606,
2000
60.
American Diabetes Association: Diabetic nephropathy (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S85
–S89,
2002
61.
Mayfield JA, Reiber GE, Sanders LJ, Janisse D, Pogach LM: Preventive foot care in people with diabetes (Technical Review).
Diabetes Care
21
:
2161
–2177,
1998
62.
American Diabetes Association: Preventive foot care in people with diabetes (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S69
–S70,
2002
63.
American Diabetes Association: Consensus Development Conference on Diabetic Foot Wound Care (Consensus Statement).
Diabetes Care
22
:
1354
–1360,
1999
64.
Aiello LP, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL, Klein R: Diabetic retinopathy (Technical Review).
Diabetes Care
21
:
143
–156,
1998
65.
The Diabetes Control and Complications Trial Research Group: Effect of pregnancy on microvascular complications in the Diabetes Control and Complications Trial.
Diabetes Care
23
:
1084
–1091,
2000
66.
Diabetic Retinopathy Study Research Group: Preliminary report on effects of photocoagulation therapy.
Am J Ophthalmol
81
:
383
–396,
1976
67.
Diabetic Retinopathy Study Research Group: Four risk factors for severe visual loss in diabetic retinopathy: the third report of the Diabetic Retinopathy Study.
Arch Opthalmol
97
:
654
–655,
1979
68.
Diabetic Retinopathy Study Research Group: Design, methods, and baseline results: DRS report no. 6.
Invest Ophthalmol Vis Sci
21
:
149
–209,
1981
69.
Diabetic Retinopathy Study Research Group: Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of Diabetic Retinopathy Study (DRS) findings: DRS report number 8.
Opthalmology
88
:
583
–600,
1981
70.
Diabetic Retinopathy Study Research Group: Indications for photocoagulation treatment of diabetic retinopathy: DRS report no. 14. Int Opthalmol Clin
27
:
239
–253,
1987
71.
Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for diabetic macular edema: ETDRS report no. 1.
Arch Opthalmol
103
:
1796
–1806,
1985
72.
Early Treatment Diabetic Retinopathy Study Research Group: Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema: ETDRS report number 2.
Opthalmology
94
:
761
–774,
1987
73.
Early Treatment Diabetic Retinopathy Study Research Group: Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: ETDRS report no. 3.
Int Ophthalmol Clin
27
:
254
–264,
1987
74.
Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for diabetic macular edema. ETDRS report no. 4.
Int Opthalmol Clin
27
:
265
–272,
1987
75.
Early Treatment Diabetic Retinopathy: Study design and baseline patient characteristics: ETDRS report number 7.
Opthalmology
98
:
741
–756,
1991
76.
Early Treatment Diabetic Retinopathy Study Research Group: Effects of aspirin treatment on diabetic retinopathy: ETDRS report number 8.
Opthalmology
98 (Suppl.):757–765, 1991
77.
Early Treatment Diabetic Retinopathy Study Research Group: Early photocoagulation for diabetic retinopathy: ETDRS report no. 9. Opthalmology 
98
:
766
–785,
1991
78.
American Diabetes Association: Diabetic retinopathy (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S90
–S93,
2002
79.
Kitzmiller JL, Gavin LA, Gin GD, Jovanovic-Peterson L, Main EK, Zigrang WD: Preconception care of diabetes: glycemic control prevents excess congenital malformations.
JAMA
265
:
731
–736,
1991
80.
Goldman JA, Dicker D, Feldberg D, Yeshaya A, Samuel N, Karp M: Pregnancy outcome in patients with insulin-dependent diabetes mellitus with preconception diabetic control: a comparative study.
Am J Obstet Gynecol
155
:
293
–297,
1986
81.
Rosenn B, Miodovnik M, Combs CA, Khoury J, Siddiqi TA: Pre-conception management of insulin-dependent diabetes: improvement of pregnancy outcome.
Obstet Gynecol
77
:
846
–849,
1991
82.
Tchobroutsky C, Vray MM, Altman JJ: Risk/benefit ratio of changing late obstetrical strategies in the management of insulin-dependent diabetic pregnancies.
Diabete Metab
17
:
287
–294,
1991
83.
Willhoite MB, Bennert HW Jr., Palomaki GE, Zaremba MM, Herman WH, Williams JR, Spear NH: The impact of preconception counseling on pregnancy outcomes.
Diabetes Care
16
:
450
–455,
1993
84.
Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner R: Preconception care of diabetes, congenital malformations, and spontaneious abortions (Technical Review).
Diabetes Care
19
:
514
–541,
1996
85.
American Diabetes Association: Preconception care of women with diabetes (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S82
–S84, 2002
86.
Colquhoun AJ, Nicholson KG, Botha NT: Effectiveness of influenza vaccine in reducing hospital admissions in people with diabetes.
Epidemiol Infect
119
:
335
–341,
1997
87.
Advisory Committee on Immunization Practices (ACIP): Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR
46(no. RR-9):1–25, 1997
88.
Advisory Committee on Immunization Practices (ACIP): Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR
46 (no. RR-8):1–25, 1997
89.
Smith SA, Poland GA: The use of influenza and pneumococcal vaccines in people with diabetes (Technical Review).
Diabetes Care
23
:
95
–108,
2000
90.
American Diabetes Association: Immunization and the prevention of influenza and pneumococcal disease in people with diabetes (Position Statement).
Diabetes Care
25(Suppl. 1)
:
S117
–S119,
2002
91.
American Diabetes Association: Care of children with diabetes in the school and day care setting.
Diabetes Care
25(Suppl. 1)
:
S122
–S126,
2002

Originally approved 1988. Most recent review/revision, October 2001.

Abbreviations: ACE, angiotensin-converting enzyme; ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; ARB, angiotensin receptor blocker; CAD, coronary artery disease; CHD, coronary heart disease; CVD, cardiovascular disease; DCCB, dihydropyridine calcium channel blocker; DCCT, Diabetes Control and Complications Trial; DKA, diabetic ketoacidosis; DRS, Diabetic Retinopathy Study; ESRD, end-stage renal disease; ETDRS, Early Treatment Diabetic Retinopathy Study; FPG, fasting plasma glucose; GCT, glucose challenge test; GDM, gestational diabetes mellitus; GFR, glomerular filtration rate; HRC, high-risk characteristic; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; MNT, medical nutrition therapy; NPDR, nonproliferative diabetic retinopathy; OGTT, oral glucose tolerance test; PDR, proliferative diabetic retinopathy; PPG, postprandidial plasma glucose; SMBG, self-monitoring of blood glucose; UKPDS, U.K. Prospective Diabetes Study.