Management of Type 2 Diabetes Mellitus

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Chapter 22

Management of Type 2 Diabetes Mellitus

A comprehensive review of all the subtleties of diabetes management is beyond the scope of any chapter. The epidemiology, pathophysiology, and diagnosis of diabetes and its complications will not be reviewed, though arguably an understanding of these issues is integral in all treatment decisions. Treatment guidelines, lifestyle interventions, pharmacotherapy, the principles of cardiovascular risk-factor management, and upcoming trials that will inform treatment decisions in the future will be examined. An excellent source of information on these issues, which is updated annually, is the American Diabetes Association’s (ADA) Clinical Practice Recommendations.1 It is published as the first supplement to the journal Diabetes Care each January and is available online at by clicking “For Health Care Professionals.”

Over the last decade, a fundamental transformation of the principles of management of type 2 diabetes has occurred. Driven by a large number of multicenter randomized clinical trials documenting improved outcomes associated with glucose, blood pressure, and lipid management, guidelines have been established for diabetes treatment; increasingly, adherence to these guidelines is monitored and in some cases enforced by insurers and health care systems. In parallel, there has been a change in the level of concern about diabetes as a public health issue, and as a result, there have been changes in attitudes among patients and providers about its treatment. This has been driven by the recognition that we are in the midst of an epidemic of diabetes, well established in the United States2 and just emerging in much of the developing world.3 The estimated lifetime risk for developing diabetes for individuals born in the year 2000 in the United States is 32.8% for males and 38.5% for females, with Hispanic Americans having estimated lifetime risks for diabetes approximating 50%.4 The morbidity, mortality, and expense associated with diabetes are staggering. In Western society, people with diabetes are three times more likely to be hospitalized than nondiabetic individuals. In the United States, diabetes is the leading cause of blindness and accounts for over 40% of the new cases of end-stage renal disease. The risk of heart disease and stroke is two to four times higher, and the risk of lower-extremity amputation is approximately 20 times higher for people with diabetes than for those without diabetes.5 Although diabetes is the seventh leading cause of death in the United States, this is clearly an underestimate. Despite the fact that over 70% of people with diabetes die of heart disease and stroke, only approximately 10% have diabetes listed as a contributing cause on death certificates.6 Tragically, this enormous burden of death and disability has not been reduced by huge health care expenditures. In fact, the epidemic of diabetes is one of the drivers of increasing health care costs, with annual disbursements for people with diabetes approximately two to three times higher than expected in the absence of diabetes and accounting for at least 10% of health care expenditures in the United States.7 There is evidence that increased effort to control diabetes and its comorbidities can even reduce costs associated with diabetes and that a public health approach to diabetes can reduce the burden of complications of diabetes.8

Fortunately, the spectrum of pharmacologic agents and glucose monitoring technology available for the treatment of diabetes have dramatically expanded, and both private and government health insurers have greatly improved the extent to which diabetes education, nutritional counseling, and diabetes equipment and supplies are covered. These trends have made it possible to achieve the recommended targets for glucose, blood pressure, and lipid therapy in the vast majority of cases. The bulk of this chapter will deal with those approaches as well as emerging treatments and clinical trials that will inform clinical decision making over the next decade.

Glucose Treatment Guidelines

Guidelines are optimally driven by the results of randomized multicenter clinical trials. Prospective randomized clinical trials have documented improved rates of microvascular complications in patients with diabetes treated to lower glycemic targets. In the U.K. Prospective Diabetes Study (UKPDS),9 patients with new-onset diabetes were treated with diet and exercise for 3 months, with an average reduction in glycosylated hemoglobin (Hb) or HbA1c (A1C) from approximately 9% to 7% (upper limit of normal 6%). Those with fasting plasma glucose (FPG) greater than 108 mg/dL (6 mM) after the dietary intervention were randomly assigned to one of two treatment policies. In the standard intervention, subjects continued the lifestyle intervention, and pharmacologic therapy was initiated only if the FPG reached 270 mg/dL (15 mM) or the patient became symptomatic. In the more intensive treatment program, all patients were randomly assigned to treatment with either sulfonylurea, metformin, or insulin as initial therapy, and doses increased in an effort to achieve an FPG less than 108 mg/dL. Additional agents were employed only if the patients became symptomatic or FPG became greater than 15 mM (270 mg/dL). As a consequence of the design, although the A1C fell initially to about 6% during the first year, over the average 10 years of follow-up, it rose to approximately 8% in the intensive treatment group. The average A1C in the standard treatment group was approximately 1% higher throughout the study. The risk of severe hypoglycemia was small—on the order of 1% to 5% per year in the insulin-treated group—and weight gain was modest; both were higher in patients randomly assigned to insulin and lower in those receiving metformin.10 Associated with this improvement in glycemic control, there was a reduction in the risk of microvascular complications (retinopathy, nephropathy, and neuropathy) in the intensive group. Although there was a trend toward reduced rates of macrovascular events in the more intensively treated group, it did not reach statistical significance.

Similar reductions in microvascular events were observed in another trial of entirely different design and much smaller size. In the Kumamoto study, Japanese patients of normal weight with type 2 diabetes treated with insulin were randomly assigned to standard treatment or an intensive program of insulin therapy designed to achieve normal glycemia. The control group maintained A1C values at approximately 9%, whereas A1C in the intensive group was reduced to approximately 7%, and that separation was maintained for 6 years. Again, there was a modest increased risk of hypoglycemia and weight gain, a reduction in microvascular complications, and a statistically non-significant trend toward reduced rates of vascular endpoints in the more intensively treated patients.11

In 2008, three studies examining the effects of two levels of glycemic control on cardiovascular endpoints in type 2 diabetes were reported. Action to Control Cardiovascular Risk in Diabetes (ACCORD),12 Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE),13 and the Veterans Affairs Diabetes Trial (VADT)14 each randomized middle-aged and older individuals at high risk for cardiovascular events. ACCORD and VADT aimed for an A1C target of less than 6%, using complex combinations of oral agents and insulin. ADVANCE aimed for an A1C target of less than or equal to 6.5%, using a somewhat less intensive approach based on the addition of the sulfonylurea gliclazide. None of the trials demonstrated a statistically significant benefit on combined vascular endpoints. ACCORD demonstrated a 22% increase in total mortality, while VADT had numerically more deaths in the intensive group (hazard ratio 1.07). Both VADTs and ADVANCE showed modest reductions in microvascular outcomes. In these studies, there were suggestions that people without clinical cardiovascular disease (CVD), shorter-duration disease and lower baseline A1C had greater benefits from the more intensive glucose-lowering strategies. Furthermore, a 10-year follow-up of the UKPDS cohort showed that the relative benefit of more intensive management of glucose at the end of the randomized portion of the trial was maintained, resulting in the emergence of statistically significant benefits on CVD endpoints and total mortality.15 Meta-analysis of cardiovascular outcomes in randomized trials suggests that with an average A1C reduction of 0.9%, there is a 17% reduction in nonfatal myocardial infarction and a 15% reduction in coronary heart disease (CHD), without significant effects on stroke or all-cause mortality. However, as discussed earlier, there is significant heterogeneity in the result with respect to mortality across trials, the etiology of which is completely uncertain.16

In Table 22-1, guidelines from the ADA1 and the American College of Endocrinology17 (ACE) are presented. The ADA, along with the American Heart Association and the American College of Cardiology Foundation, examined the results of the recently published cardiovascular outcomes studies.18 They reaffirmed the general A1C goal of less than 7% to reduce the incidence and progression of microvascular disease. Though no trial has demonstrated CVD benefit to improved glycemic control, they suggested that the general goal of less than 7% appeared reasonable from the perspective of macrovascular disease risk. However, they highlighted the need for individualization, suggesting that lower A1C goals than the general goal of less than 7% could be suggested for patients with short-duration disease, long life expectancy, and no significant CVD, if they could be achieved without significant hypoglycemia or other adverse effects of treatment. Furthermore, they suggested that less stringent goals may be appropriate for those with a history of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbid conditions, or those who have difficulties achieving the general A1C target of less than 7% despite concerted effort, including patient education, monitoring, and effective doses of multiple glucose-lowering agents including insulin.

With respect to fasting, premeal, or postprandial targets, there is little support for any particular level of glycemic control in the management of type 2 diabetes insofar as no large-scale outcome study has targeted particular levels of glucose with home glucose monitoring. The ADA target of fasting and premeal plasma glucose levels of 70 to 130 mg/dL (3.9 to 7.2 mM) is based on an estimate of the range of average glucose values that would be associated with a low risk of hypoglycemia and an A1C less than 7%. The American College of Endocrinology target of less than 110 mg/dL (6 mM) is an effort to achieve normal levels of glycemia. However, it should be recognized that consistent fasting and premeal glucose levels less than 110 mg/dL would be expected to be associated with an HbA1c of approximately 5.5% or lower.19

There are limited studies in which even safety, much less a clinical outcome, is documented for targeting a particular level of postprandial glucose. There are effective A1C-lowering agents that primarily target postprandial glucose levels. Monitoring postprandial glucose levels may allow more effective dose adjustment of these agents, though even this has not been demonstrated in clinical trials. Certainly there are patients with diabetes who have average fasting glucose levels within targets but whose A1C remains elevated. Monitoring and specifically treating postprandial elevations in these patients may provide improvements in A1C, perhaps with a lower risk of hypoglycemia and weight gain than further lowering fasting and premeal glucose levels. The ACE guidelines recommend targeting a 2-hour postprandial glucose level less than 140 mg/dL (7.8 mM) in an effort to achieve near-normal glycemia. Consistent postprandial glucose values less than 140 mg/dL would be associated with average A1C levels of approximately 5% or lower; 2-hour postprandial glucose levels of less than 180 mg/dL (10 mM) would generally be associated with A1C levels of 6% to 7% and is the recommended postprandial target of the ADA.1,19

Lifestyle Intervention

The components of lifestyle intervention include comprehensive diabetes education aimed at enabling patients to self-manage their diabetes, medical nutrition counseling, and exercise recommendations. The appropriate paradigm of care in diabetes is patient focused, since patients are responsible for almost every diabetes-related decision and behavior. Providers at their best can provide advice and help recognize and suggest techniques to overcome obstacles to achieving treatment goals.

Education of Patients

Arguably, over the last 10 years, nothing has changed more fundamentally in diabetes care than the emphasis on lifestyle intervention. For decades, physicians and patients paid lip service to the notion that lifestyle intervention is important. Now we have significant clinical trial evidence that each component of lifestyle intervention, when appropriately administered, can contribute to improved outcomes.20,21 Furthermore, since the Balanced Budget Act of 1997 and the passage of complementary legislation by most state governments, lifestyle intervention has become a covered benefit for most patients with diabetes in the United States.

Diabetes is a lifelong disease, and health care providers have almost no control over the extent to which patients adhere to the day-to-day treatment regimen. The appropriate role of the health care provider is to serve as a coach to the patient, who has primary responsibility for the delivery of daily care. Thus, it is essential that health care professionals understand the context in which patients are taking care of their disease. Using a prescriptive approach in which patients are told what to do can work on occasion but fails more often than not because of unrecognized barriers to the execution of a particular plan.

As defined by the ADA,22 diabetes self-management education is the process of providing the person with diabetes the knowledge and skills needed to perform self-care, manage crises, and make lifestyle changes. As a result of this process, the patient must become a knowledgeable and active participant in the management of his or her disease. To achieve this rather daunting goal, patients and providers work together in a long-term, ongoing process. Comprehensive diabetes education should be individualized, with emphasis on the issues highlighted in Table 22-2. There are many more specialized topics relevant to almost all patients, such as how to adjust therapy when eating out or during travel, as well as how to access available local health care resources and negotiate the complexity of health care financing in the United States. Although only limited studies are published to date, as a body of work, they do provide support for the concept that diabetes education can be cost effective and can improve outcomes.2123

A team of providers is generally required to optimally implement the process of diabetes self-management education, because the amount of information that needs to be exchanged is large and the range of expertise required is broad. It is generally impossible to cover the recommended content fully in the context of several or even many brief encounters with a physician in an office setting. Potential providers in a team care approach could include nurses, dietitians, exercise specialists, behavioral therapists, pharmacists, and other medical specialists including diabetologists or endocrinologists, podiatrists, medical subspecialists, obstetrician-gynecologists, psychiatrists, and surgeons. In the diabetes self-care process, the potential role of the community where the patient lives and works is enormous. At a minimum, this community includes family, friends, employers, health care systems, and health care insurers. Each member of the team has a role to play in the process, and it is useful to review these roles frequently (Table 22-3). The primary role of the providers in this process is to provide guidance in goal setting to manage the risk of complications, suggest strategies to achieve goals and techniques to overcome barriers, provide training in skills, and screen for complications. For this process to be a success, the patient must commit to the principles of self-care, participate fully in the development of a treatment plan, make ongoing decisions regarding self-care from day to day, and communicate honestly and with sufficient frequency with the team.

Fortunately, barriers to providing team care are becoming less daunting, in large measure because of the rapidly expanding number of diabetes education programs and improved insurance coverage for services. The American Association of Diabetes Educators (800-TEAM-UP4; and the ADA (800-DIABETES; can provide information regarding diabetes educators and education programs nationwide.

For diabetes care to be effective, communication and mutual respect among the patient-centered team is critical. Unfortunately, in many communities, the full benefit of the consultation and ongoing care with diabetes educators, nurses, dietitians, pharmacists, medical consultants, and primary care providers is not achieved because of overly hierarchical approaches to care. Non–health care professionals, such as lay or peer supporters, can provide benefit to patients in developing effective diabetes self-care behaviors. Key functions of such efforts have been identified and include assistance in managing and living with diabetes in daily life, social and emotional support, and linkage to clinical care.23

Perhaps some of the most overlooked contributors to ineffective care in the setting of type 2 diabetes are the relatively common barriers created by psychiatric, neurocognitive function, and adjustment disorders, which are largely responsive to psychosocial therapies.24


The ADA has published technical reviews that exhaustively document the literature regarding the effect of medical nutrition therapy and specific advice on diabetes-related outcomes such as A1C and weight, as well as a position statement.25-27 These are summarized in Table 22-4. An individually negotiated nutrition program in which each patient’s circumstances, preferences, cultural background, and the overall treatment program are considered is most likely to result in optimal outcomes. Ideally, a registered dietitian with specific skill and experience in implementing nutrition therapy in diabetes management should work collaboratively with the patient and other health care team members in providing medical nutrition therapy. For optimum outcomes, this counseling should be performed over a series of visits initially, with intermittent follow-up thereafter. Analogously, physicians and other members of the health care team need to support the nutritional plan developed collaboratively.

Table 22-4

ADA Nutritional Principles and Recommendations


• Foods containing carbohydrate from whole grains, fruits, vegetables, and low-fat milk should be included in a healthy diet.

• With regard to the glycemic effects of carbohydrates, the total amount of carbohydrate in meals or snacks is more important than the source or type. However, attention to glycemic index can provide additional benefit over that observed when total carbohydrate is considered alone.

• Since sucrose does not increase glycemia to a greater extent than isocaloric amounts of starch, sucrose, and sucrose-containing foods in the context of a mixed meal, they do not need to be restricted by people with diabetes; however, they should be substituted for other carbohydrate sources in the context of an appropriate meal plan or, if added, covered with insulin or other glucose-lowering medication.

• Nonnutritive sweeteners are safe when consumed within the acceptable daily intake levels established by the U.S. Food and Drug Administration.

• Individuals receiving fixed daily insulin doses should try to be consistent in day-to-day carbohydrate intake.

• Individuals receiving intensive insulin therapy should adjust their premeal insulin doses based on the carbohydrate content of meals.

• As with the general public, consumption of dietary fiber is to be encouraged; however, there is no reason to recommend that people with diabetes consume a greater amount of fiber than others.

• Low-carbohydrate diets are not recommended in the management of diabetes, though they can be useful in reducing triglycerides. Although dietary carbohydrate is the major contributor to postprandial glucose concentration, it is an important source of energy, water-soluble vitamins and minerals, and fiber. Restricting total carbohydrate to less than 130 g/d is not recommended.


• Less than 10% of energy intake should be derived from saturated fats. Some individuals (i.e., persons with LDL cholesterol ≥100 mg/dL) may benefit from lowering saturated fat intake to <7% of energy intake.

• Dietary cholesterol intake should be <300 mg/d. Some individuals (i.e., persons with LDL cholesterol ≥100 mg/dL) may benefit from lowering dietary cholesterol to <200 mg/d.

• To lower LDL cholesterol, energy derived from saturated fat can be reduced if weight loss is desirable or replaced with either carbohydrate or monounsaturated fat when weight loss is not a goal.

• Intake of trans unsaturated fatty acids should be minimized.

• Reduced-fat diets, when maintained long term, contribute to modest loss of weight and improvement in dyslipidemia.

• Two to three servings of fish per week provide dietary n-3 polyunsaturated fat and can be recommended.

• Polyunsaturated fat intake should be ≈10% of energy intake.

Energy Balance

• In insulin-resistant individuals, reduced energy intake and modest weight loss improve insulin resistance and glycemia in the short term.

• Weight loss is recommended for all overweight (BMI 25-29.9 kg/m2) or obese (BMI ≥ 30.0 kg/m2) adults who have, or who are at risk for developing, type 2 diabetes. The primary approach for achieving weight loss is therapeutic lifestyle change, which includes a reduction in energy intake and an increase in physical activity.

• A moderate decrease in caloric intake (500-1000 kcal/d) will result in a slow but progressive weight loss (1-2 lb/wk). For most patients, weight-loss diets should supply at least 1000-1200 kcal/d for women and 1200-1600 kcal/d for men.

• Structured programs that emphasize lifestyle changes, including education, reduced fat (<30% of daily energy) and energy intake, regular physical activity, and regular participant contact, can produce long-term weight loss on the order of 5%-7% of starting weight.

• Exercise and behavior modification are most useful as adjuncts to other weight-loss strategies. Exercise is helpful in maintenance of weight loss.

• Standard weight reduction diets, when used alone, are unlikely to produce long-term weight loss. Structured intensive lifestyle programs are necessary.

Adapted from Klein S, Sheard NF, Pi-Sunyer X, et al: Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies: a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition, Diabetes Care 27:2067–2073, 2004; Gillespie SJ, Kulkarni KD, Daly AE: Using carbohydrate counting in diabetes clinical practice, J Am Diet Assoc 98:897–905, 1998; and Egede LE, Ye K, Zhang D, et al: The prevalence and pattern of complementary and alternative medicine use in individuals with diabetes, Diabetes Care 25:324–329, 2002.

Individualized dietary advice can be developed by a physician from a brief diet history obtained by asking: “What do you eat for breakfast? … lunch? … supper? Do you have snacks between breakfast and lunch? … lunch and supper? … supper and bedtime? What do you drink during the day?” Ideally, this information should be obtained at each visit, with specific suggestions for change that both patient and provider agree are important in the context of the overall treatment plan as well as both achievable and sustainable. Easy issues to address include caloric beverages, which tend to elevate glucose levels dramatically and can generally be replaced relatively easily with artificially sweetened alternatives. Juices are generally perceived as healthy but can significantly affect glycemic control and total caloric intake. Portion control and recipe modification are excellent dietary techniques, particularly for meats and fried foods. Substituting low-fat products for higher-fat foods is often useful but needs to be done with the recognition that they are generally higher in carbohydrates. It is important that patients recognize that “fat-free” and “sugar-free” foods are not “free” and that attention to both total carbohydrate and calorie content are critical.

Eating approximately every 4 hours while awake is the most practical dietary plan for most overweight people. Frequent small meals have been shown to be of benefit when used in a controlled inpatient setting, but in general when overweight patients are encouraged to eat more frequently they often overeat more frequently. At a minimum, avoiding high-calorie snacks is reasonable advice for most people with diabetes. If all health care providers repeatedly obtain a diet history every few weeks to months, effective assessment of whether previously agreed-to changes were enacted, reinforcement of the importance of dietary efforts, and the patient’s gradual evolution to a more healthful diet through further dietary modification can be accomplished.

In general, the critical nutrient for glycemic control is carbohydrate. Essentially all carbohydrates consumed are converted to glucose in the gut and require the action of insulin to be cleared from the circulation. A dietary technique called carbohydrate counting can be used in patients with type 2 diabetes to facilitate consistent carbohydrate intake or to allow insulin dose adjustment in response to changes in carbohydrates consumed.28 Although this technique requires less insulin than fixed meal dosing and may help curb weight gain, it has not been shown to improve glycemic control or reduce the rate of hypoglycemia in patients with type 2 diabetes.29 Whereas the β cell in type 2 diabetes has generally lost its responsiveness to glucose, the second phase of insulin secretion is largely spared in type 2 diabetes and is in part driven by amino acids and fatty acids. Therefore, including some protein and fat in each meal and snack may be useful.

Dietary fat is the nutrient most closely associated in epidemiologic studies with the risk of developing type 2 diabetes. Although dietary fat clearly has a major impact on total caloric intake, as well as on circulating lipids, it has a minimal acute impact on glycemia. It is recommended that people with diabetes, if they are overweight, consume a diet modestly restricted in calories, with less than 10% of total calories as saturated fat, less than 10% as polyunsaturated fat, and total avoidance of trans fats. Some advocate substituting foods high in monounsaturated fatty acids—seeds, nuts, avocado, olives, olive oil, and canola oil—for carbohydrate, but most patients do not find adequate variety in the monounsaturated fatty acid category and often overeat these high-caloric-density foods.

Dietary protein similarly has a minimal impact on glucose levels, although as mentioned, amino acids do promote insulin secretion. Metabolism of protein results in the formation of acids and nitrogenous waste that may result in bone demineralization and glomerular hyperfiltration. At least 0.8 g of high-quality protein per kilogram is generally recommended. Protein restriction in the setting of kidney disease has been recommended and is more fully discussed in Chapter 28. There is no evidence that protein intake materially effects the risk of developing kidney disease in patients with diabetes.

The role of vitamins, trace minerals, and nutritional supplements in the treatment of diabetes is poorly understood. There are some patients and providers who are absolutely convinced of the utility of soluble fiber, magnesium, chromium, zinc, folic acid, pyridoxine, cyanocobalamin, vitamin A, vitamin C, vitamin E, vanadium, selenium, garlic, and others. Clinical trial data to support their safety and efficacy are inconclusive. Many patients are convinced that nutritional supplementation is healthful, and it is often counterproductive to engage in scholarly discussion of the nature of the evidence base for their decision. At a minimum, discussion should include the documented efficacy of lifestyle and pharmacologic interventions and the idea that these efforts should not be left by the wayside when budgetary constraints affect potentially more effective interventions.30,31 A multivitamin/mineral preparation may be reasonable for most patients with diabetes. A recent randomized control trial in patients with diabetes demonstrated fewer self-reported infections and related absenteeism.32 Studies demonstrating the benefits of B-vitamin supplementation on restenosis after angioplasty33 have recently been called into question; the possibility has been raised that such therapy could increase rates of restenosis after stent placement.34

Although there are proponents of a wide range of dietary composition, there are few data to support these recommendations from long-term outcome studies of prescribed diets. Mixed meals containing 10% to 20% of calories from protein, no more than 10% of calories from saturated fat, no more than 10% from polyunsaturated fats, and the remainder largely from monounsaturated fats (seeds, nuts, avocados, olives, olive oil, canola oil) and carbohydrates, particularly whole grains, fruit, vegetables, and low-fat milk, are probably most reasonable. High-carbohydrate, low-fat diets, although historically recommended by many health organizations, have been shown to increase postprandial blood glucose and triglyceride levels, elevate fasting triglyceride levels, and decrease high-density lipoprotein (HDL) cholesterol levels in insulin-resistant people, including those with type 2 diabetes. Several studies have demonstrated improved lipid levels and blood glucose control in both short- and intermediate-term studies in which total fat intake approaches 45% of calories and carbohydrate intake is as low as 40% of calories. Reducing fat or carbohydrate intake in obese individuals will not necessarily lead to reduced calories. Since weight loss will occur only in the setting of caloric restriction, arguably the most appropriate approach is to limit intake of both fat and highly processed, easily digestible carbohydrates. The treatment of obesity is discussed in Chapter 2; the principles discussed are appropriate when type 2 diabetes is complicated by obesity. To date, short-term studies of medical nutrition therapy, physical activity, and comprehensive lifestyle approaches have been shown to improve the control of classic CVD risk factors, as well as intermediate markers of CVD risk such as C-reactive protein; no long-term, large-scale study of intentional weight loss has been powered to examine CVD endpoints. Look AHEAD (Action for Health in Diabetes) will examine CVD events for up to 11.5 years in a study in which patients with type 2 diabetes 45 to 74 years of age with a body mass index = 25 kg/m2 will be recruited. Patients will be randomized to a 4-year intensive weight loss program (calorie restriction and physical activity) or to diabetes support and education. With planned recruitment of 5000 patients at 16 centers over 2.5 years, the study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between arms.35


There is a substantial body of literature supporting exercise as a modality of treatment in type 2 diabetes, including a recent technical review by the ADA.36,37 The recommendations of this technical review are summarized in Table 22-5. Exercise is perhaps the single most important lifestyle intervention in diabetes, because it is associated with improved glycemic control, insulin sensitivity, cardiovascular fitness, and cardiac remodeling. Aerobic exercise and resistance (strength) training both have a positive impact on glucose control. Improvements in glycemic control are generally apparent immediately, become maximal after a few weeks of consistent exercise, but only persist for 3 to 6 days after the cessation of training. To maintain effects on glycemia, a minimum of three exercise sessions a week is suggested, with no more than 2 days rest between sessions.

Table 22-5

ADA Recommendations Regarding Physical Activity in People with Type 2 Diabetes

Indications for Graded Exercise Test With ECG Monitoring

In the absence of contraindications, a graded exercise test with ECG monitoring should be seriously considered before undertaking aerobic physical activity with an intensity exceeding the demands of everyday living (more intense than brisk walking) in previously sedentary diabetic individuals whose 10-year risk of a coronary event is ≥10%. This risk could be estimated directly using the UKPDS Risk Engine ( and would correspond approximately to meeting any of the following criteria:

These criteria should not be construed as a recommendation against stress testing for individuals without the above risk factors or for those who are planning less intense exercise. [Note: The most recent ADA recommendations 1 do not advocate routine stress testing in this setting.]

Aerobic Exercise

The amount and intensity recommended for aerobic exercise vary according to goals.

• To improve glycemic control, assist with weight maintenance, and reduce risk of CVD, recommend at least 150 min/wk of moderate-intensity aerobic physical activity (40% to 60% of VO2max or 50% to 70% of maximum heart rate) and/or at least 90 min/wk of vigorous aerobic exercise (>60% of VO2max or >70% of maximum heart rate). The physical activity should be distributed over at least 3 days/wk and with no more than 2 consecutive days without physical activity.

• Performing ≥4 hr/wk of moderate to vigorous aerobic and/or resistance exercise is associated with greater CVD risk reduction compared with lower volumes of activity.

• For long-term maintenance of major weight loss (≥13.6 kg [30 lb]), larger volumes of exercise (7 hr/wk of moderate or vigorous aerobic physical activity) may be helpful.

CAD, Coronary artery disease; CVD, cardiovascular disease; ECG, electrocardiograph.

Adapted from Sigal RJ, Kenny GP, Wasserman DH, et al: Physical activity/exercise and type 2 diabetes, Diabetes Care 27:2518–2539, 2004.

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