For years, the traditional cornerstones of therapy for patients with DM have been dietary modification and medication. Exercise also has been encouraged in patients with DM because regular physical activity may help to control hyperglycemia through improved glucose utilization. However, a variety of factors can influence the effect that exercise can have on blood glucose. Variables that should be considered include the type of diabetes involved (type 1 versus type 2), the type of exercise performed (aerobic versus anaerobic), the duration and intensity of physical activity, concurrent use of medications (e.g., sulfonylureas, insulin), and the patient’s baseline cardiorespiratory fitness level (8).

In order to better understand the effect that exercise can have on glycemic control, it is important to appreciate the relation between exercise and glucose utilization. In normal human metabolism, during a single episode of exercise, the muscles initially utilize glucose in the muscle and later convert muscle glycogen to glucose to provide energy. Exercise then stimulates an insulin-independent transport of glucose from the circulation into the exercising muscle. As the blood glucose concentration drops, insulin secretion decreases and the release of glucagon increases. These hormonal changes result in enhanced hepatic glucose production secondary to increased glycogenolysis and to gluconeogenesis. With further exercise, other counter-regulatory hormones (e.g., epinephrine, norepinephrine, growth hormone, and cortisol) begin to play a role in maintaining adequate blood glucose levels (9).

With regular moderate-intensity physical activity, training-effects occur that result in more efficient use of energy by muscle. These changes include the development of new muscle capillaries and increases in the quantity of mitochondrial enzymes (9). Studies have also demonstrated that regular endurance exercise training increases the concentration of GLUT4 mRNA and protein in skeletal muscle. GLUT4 is a protein that serves as a glucose transporter. The exercise-related increase in muscle GLUT4 is physiologically important because elevated GLUT4 augments muscle glucose transport and enhances whole-body glucose tolerance (10).

GLUT4 is predominantly found in association with intracellular vesicles that translocate to the cell membrane in order to increase glucose transport. The maximal rate of muscle glucose transport is determined by both the total number of GLUT4 molecules and the proportion of these molecules that are translocated to the cell membrane in response to insulin and/or muscle contraction (10). It has been demonstrated that in type 2 diabetes, impairment of insulin-stimulated GLUT4 translocation exists. This defect is felt to be one of the primary contributors to diabetes-related insulin resistance. In contrast, there does not appear to be any decrement in muscle contraction-induced translocation of GLUT4 during exercise (11).

In patients with DM, several physiological responses to exercise are altered based upon the plasma insulin concentration at the time of exercise and the degree of pre-exercise glycemic control. Additionally, the use of exogenous insulin can have a profound effect on glucose concentrations during exercise. Well-controlled diabetic patients on insulin therapy often will have a much larger drop in blood glucose concentrations than that seen in non–insulin dependent diabetic patients or individuals without diabetes. Because the effects of exogenous insulin cannot be turned off, muscle glucose uptake and the inhibition of hepatic glucose production may continue to occur despite dropping levels of blood glucose (9).

In patients with poor glucose control, exercise can actually result in blood glucose elevations. This occurs when inadequate amounts of insulin result in impaired glucose uptake by muscle and when hormones such as epinephrine, cortisol, and growth hormone, which are released during exercise, cause increased hepatic glucose production (9).

With regard to the long-term effects of routine exercise on glucose control, the effects differ between patients with
type 1 DM and those with type 2 DM. The results of several studies have found that exercise interventions can reduce glycosylated hemoglobin levels (HbA_Ic) in people with type 2 DM. Many of the studies demonstrating a beneficial effect of regular aerobic exercise on long-term glucose control in type 2 DM have utilized physical activity performed for 30 to 60 minutes, at 50% to 80% of maximal oxygen uptake (Vo_2max), three to four sessions per week. With this type of exercise program, reductions in HbA_Ic of 10% to 20% from baseline could be achieved (12).

Studies utilizing resistance training have also demonstrated a beneficial effect on long-term glucose control in type 2 DM. Eriksson et al. (13) examined the effects of an individualized progressive resistance-training program. Subjects performed circuit-type resistance exercises two times per week. After 3 months of training, the average HbA_Ic dropped from 8.8% to 8.2% (p <0.05). The investigators found that glycemic control correlated strongly with changes in muscle size, quantified using magnetic resonance imaging. More recently, Castaneda et al. (14) evaluated the use of a high-intensity progressive resistance-training program on glycemic control in type 2 diabetic patients with a mean age of 66 years. The investigators performed a 16-week randomized controlled trial using multiple exercises, performing three sets, three times per week. The results showed a statistically significant reduction in HbA_Ic levels from 8.7% to 7.6%, increase in muscle glycogen stores, and decrease in dosages of prescribed diabetes medication in 72% of the exercisers (p = 0.004 – 0.05) compared to a control group.

In 2001, Boule et al. (15) published a meta-analysis of controlled trials that evaluated the effects of exercise interventions (duration >8 weeks) on glycemic control in patients with type 2 DM. Twelve aerobic training studies and two resistance-training studies were included in the analysis. The investigators found that the weighted mean postintervention HbA_Ic was lower in the exercise groups compared with control groups (7.65% versus 8.31%, p <0.001). It is important to note that the difference in postintervention body mass between exercise groups and control groups was not statistically significant. The same authors published a subsequent meta-analysis in 2003 showing that exercise intensity predicted a greater postintervention weighted mean difference in HbA_Ic (r = -0.91, p = 0.002) than exercise volume (r = -0.46, p = 0.26) (16). These results suggest that increasing exercise intensity may achieve even greater benefits in glycemic control. The weighted mean difference in HbA_Ic of -0.66 demonstrated between the exercise and control groups in the first study, and -0.91 in the high intensity group in the second, has important clinical implications. This degree of improvement in glycemic control is associated with significant reductions in diabetic complications. Results of the United Kingdom Prospective Diabetes Study (UKPDS) published in 1998 (17,18) demonstrated a continuous relation between the risks of microvascular and cardiovascular complications and glycemia. For every percentage point decrease in HbA_Ic (e.g., 9%–8%) there was a 35% reduction in the risk of microvascular complications, a 25% reduction in diabetes-related deaths, an 18% reduction in combined fatal and nonfatal myocardial infarction, and a 7% reduction in all-cause mortality.

In contrast to the response in type 2 DM, improvement in long-term glucose control through exercise training in type 1 DM has not been demonstrated as clearly (19). Presumably this is due to the lesser importance of insulin resistance in these patients (9). Studies have demonstrated that in patients with type 1 DM a single bout of exercise can have a blood glucose lowering effect. As determined by HbA_Ic values, these effects of exercise, in isolation, have not typically been shown to result in long-term improvement in glucose control (12,20,21). However, a recent study by Herbst et al. (22) evaluated the effect of regular physical activity on glycemic control in type 1 diabetic patients aged 3 to 20 years. In this cross-sectional analysis of data for 19,143 patients, the authors grouped subjects by the frequency of regular physical activity (none versus one to two times per week versus three or more times per week). They found that HbA_Ic values were greater in the groups without regular physical activity compared to those with regular physical activity of three or more times per week (8.4% versus 8.1% respectively, p <0.001). Multiple regression analysis showed that regular physical activity was one of the most important factors influencing HbA_Ic. Despite these results, intensive insulin therapy and/or dietary restriction still need to be implemented to achieve adequate glycemic control (23).

Despite the apparent inadequacy of exercise to improve long-term glycemic control in patients with type 1 DM, physical activity is associated with a decreased risk of overall-mortality in this population. The benefits of physical activity on overall-mortality were demonstrated in a cohort of 548 type 1 diabetic patients enrolled in the Pittsburgh Insulin-Dependent Diabetes Mellitus Morbidity and Mortality Study (24). Physical activity was measured by survey in 1981, and mortality was ascertained through 1988. After controlling for numerous potential confounders (e.g., age, body mass index [BMI], tobacco use, etc.), the investigators found that overall activity level was inversely related to mortality risk. Sedentary males (energy expenditure <1,000 kcal/week) were three times more likely to die than active males (energy expenditure <1,000 kcal/week).

The beneficial effect of physical activity on overall-mortality has also been demonstrated in type 2 diabetics. Wei et al. (25) performed a prospective cohort study of over 1,200 men with type 2 DM. The subjects completed a maximal exercise treadmill test to determine cardiopulmonary fitness. Based on performance, subjects were categorized as “low fit, moderately fit, or high fit.”
Participants also completed an extensive self-report of personal and family history, including physical activity patterns. These individuals were followed-up for an average of 11.7 years. Adjustments were made for a variety of factors that might affect overall mortality (e.g., age, tobacco use, hypercholesterolemia, hypertension, etc.). The investigators found that the low-fitness group had an adjusted risk for all-cause mortality of 2.1 (95% CI, 1.5–2.9) compared with fit men. Additionally, men who reported being physically inactive had an adjusted risk for all-cause mortality of 1.7 (95% CI, 1.2–2.3) compared with men who reported being physically active. Another recent study showed diabetic men in the lowest, second, and third quartiles of cardiorespiratory fitness to have an overall mortality risk, that is, 4.5, 2.8, and 1.6-fold, respectively, greater than men in the highest quartile for fitness (26).

Independent of its action of blood glucose control, regular exercise can have several beneficial effects for patients with DM. One area in which exercise can have a significant impact is in cardiovascular disease risk reduction. In patients with both type 1 and type 2 DM, routine exercise can decrease risk factors for cardiovascular diseases such as dyslipidemia, hypertension, and coagulation abnormalities (21). Additionally, participation in regular physical activity may help promote reductions in tobacco use and alcohol consumption (21). Regular exercise has also been shown to have mental health benefits for diabetic patients. Although difficult to determine, routine exercise has been associated with an elevated “sense of well-being,” increased “self-esteem,” and an enhanced “quality of life” (21). Some of these psychological benefits may be derived from the ability of active participation in exercise and organized sports activities to promote socialization and peer acceptance (27). As a result, the American Diabetes Association (ADA) concludes its position statement on diabetes and exercise (12) by stating, “all patients with diabetes should have the opportunity to benefit from the many valuable effects of physical activity.”

Although exercise can be highly beneficial for patients with DM, at the same time, it can pose certain risks (see Table 7A.1). Before initiating an exercise program, individuals with diabetes should undergo a medical evaluation to screen for microvascular and macrovascular complications that may be exacerbated by exercise (12). A complete discussion of all the exercise-associated risks for diabetic patients and the specific recommendations regarding the preparticipation medical evaluation of these individuals is beyond the scope of this chapter. This information can be found in several recent publications (7,12,27). However, this section will review two of the major complications, hypoglycemia and myocardial ischemia, which are seen in diabetic patients who exercise.

Hypoglycemia remains the most common risk encountered for diabetic patients who exercise. Although this can occur in patients with type 2 DM, particularly those taking sulfonylureas, it is of greater concern in patients taking exogenous insulin. Because the effects of exogenous insulin continue despite declining blood glucose levels, muscle glucose uptake and the inhibition of hepatic glucose production may continue, resulting in profound hypoglycemia. Additionally, many diabetic patients, particularly those that have had the disease for 5 years or more, have impaired counter-regulatory mechanisms for combating hypoglycemia (27). Exercise can also enhance the absorption of exogenous insulin, particularly if it has been injected into an exercising extremity. This can further increase the risk of exercise-related hypoglycemia (27).

Even if blood glucose levels remain stable during exercise, patients with diabetes may subsequently develop delayed hypoglycemia. This often occurs at night, 6 to 15 hours after exercise, but may develop as late as 28 hours after exercise. This insidious drop in blood glucose results from the residual effect of exercise-enhanced insulin sensitivity. Additionally, hepatic glycogen synthesis to replenish stores depleted by exercise may also contribute to delayed hypoglycemia. Because liver glycogen is replaced more slowly than muscle glycogen, carbohydrate requirements may be increased for up to 24 hours after prolonged exercise (27). Strategies to help reduce the risk of exercise-related hypoglycemia are outlined in Table 7A.2.

Another concern for diabetic patients who exercise is the development of myocardial ischemia or sudden death. These adverse events are related to underlying atherosclerotic coronary artery disease. In many diabetic patients, atherosclerosis is more extensive and develops earlier than in the general, nondiabetic population. Although routine exercise can help improve many of the risk factors for coronary artery disease and decrease the long-term risk of developing cardiovascular disease, there is an actual transient increased risk for myocardial infarction, cardiac arrest, and sudden death during vigorous physical activity (29).

The ADA has recommended a graded exercise stress test if a patient, about to embark on a moderate- to high-intensity exercise program, is at high risk for underlying cardiovascular disease based on specific criteria (see Table 7A.3). If patients will only be participating in low-intensity physical activities (<60% maximal heart rate), formal exercise stress testing may not be necessary, although appropriate clinical judgment needs to be executed (12).

Additionally, in patients with known coronary artery disease, the ADA recommends that these individuals undergo a supervised evaluation of the ischemic response to exercise, ischemic threshold, and the propensity to arrhythmia during exercise (12). It is important to remember that even patients who are identified as low risk for exercise-related complications and are participating in low- to moderate-intensity activities cannot be completely assured that such activity will not acutely increase the risk of an adverse cardiac event. Nevertheless, it does appear that the long-term health benefits of regular exercise outweigh the acute cardiovascular risks. Therefore, regular exercise should be encouraged in this population of diabetic patients.