Regular physical exercise in patients with type II diabetes mellitus

DM is the general designation for a collection of endocrine disorders with different kinds of pathogenesis. The American Diabetes Association and the World Health Organization (WHO) identified new classification criteria of diabetes mellitus in 1997. This classification includes four clinical categories named “type I DM,” “type II DM,” “other specific types of DM,” and “gestational DM” [30].

Type I diabetes mellitus (also known as insulin-dependent diabetes mellitus or juvenile diabetes) mainly results from the destruction of beta cells in the pancreatic Langerhans’ islets, leading to an insulin deficiency; the onset of this type is usually at younger ages and normally requires insulin supplementation [30, 32]. Type II diabetes mellitus (also known as non-insulin-dependent diabetes mellitus) could be the result of inadequate insulin secretion, insulin resistance in peripheral tissues, or excessive hepatic glucose production [16, 30, 32], which impair glucose tolerance (hyperglycemia); this variant usually occurs in individuals aged more than 40 years with a family history of DM, and apart from the genetic predisposition, the occurrence of this type of disease is correlated with physical inactivity and being overweight [5, 16, 17, 32]. The category “other specific types of DM” consists of all particular cases of disease where genetic defects are responsible for beta cell dysfunction (maturity onset diabetes in youth) or for insulin resistance in target tissues, and of all DM situations resulting from endocrinological pathologies or pancreatic dysfunction induced by drugs/toxics or infections [5]. Gestational diabetes mellitus occurs during pregnancy and is the result of a relative insulin deficiency at the last stage of pregnancy [5].

According to the WHO recommendations (see Table 2), a positive outcome in two of the following tests to be carried out on different days, constitutes the criteria for diabetes mellitus diagnosis (Fig. 1) [30]: (1) the existence of suspected symptoms of DM and the occurrence of plasma glucose levels higher than 200 mg/dl (or 11.1 mmol/l), measured any time of the day regardless of the time that passed after the last meal; (2) the occurrence of a fasting plasma glucose level higher than 126 mg/dl (or 7.0 mmol/l); and (3) a plasma glucose level higher than 200 mg/dl (or 11.1 mmol/l) 2 h after beginning an oral glucose tolerance test (OGTT). OGTT is recommended when fasting plasma glucose levels are between 5.5 and 7.7 mmol/l.

Table 2

The WHO criteria for DM diagnosis (adapted from Mayfield [30])

	Fasting plasma glucose		Plasma glucose 2 h after beginning OGTT		Casual plasma glucose
	mg/dl	mmol/l	mg/dl	mmol/l	mg/dl	mmol/l
Normal	<110	<6.1	<140	<7.75
IFG	≥110<126	≥6.1<7.0
IGT			≥140<200	≥7.75<11.1
DM	≥126	≥7	≥200	≥11.1	>200	>11.1

IFG Impaired fasting glucose, IGT impaired glucose tolerance, DM diabetes mellitus, OGTT oral glucose tolerance test

Causal plasma glucose is defined as the glucose levels measured anytime of the day, regardless of the time passed after the last meal

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The condition of impaired glucose tolerance (IGT) is defined when fasting plasma glucose levels are higher than normal levels but too low to reach the criteria for DM diagnosis.

The goal of DM treatment is directed toward glycemic control, the correction of all metabolic and functional abnormalities such as dyslipidemia, hypertension, and obesity, and the control of morbidity and mortality related with the disease [8]. Apart from medication, the standard therapeutic procedures for the treatment of type II DM include correct dietary control and regular exercise [8, 9, 25, 35]. According to these authors, the management of each patient should be individualized and adjusted to age, medical history, earlier physical activity, eating habits, and sociocultural factors. Especially before starting an exercise program, a medical examination is necessary to detect other diseases or diabetic complications that might represent contraindications.

Important sources of energy for living organisms are carbohydrates and especially glucose, and low blood glucose can cause loss of consciousness, seizures, and death. On the other hand, chronically elevated concentrations in blood glucose can result in blindness, renal failure, cardiac and peripheral vascular diseases, and neuropathy [17]. Therefore, blood glucose concentrations should be maintained within narrow limits to prevent complications. During fasting, the physiological blood concentrations of glucose are maintained by the liver. In the postprandial state, the rise in blood glucose concentration stimulates insulin secretion, which reduces hepatic glucose production and increases membrane glucose transporters (GLUT) in peripheral tissues, thus reducing blood glucose [11, 13, 24, 26].

During exercise, and compared to the basal status, recruited skeletal muscles require four- to fivefold more energy for contraction, using blood glucose, muscle glycogen, and fatty acids derived from adipose tissue as metabolic fuel [37]. Muscle glycogen serves as the main fuel source during strenuous and short-term exercise in healthy subjects. When the duration of exercise is prolonged, muscle energy is predominantly derived from blood-born glucose and from fatty acids produced in the adipose tissue [37, 49, 52]. Enhanced plasma levels of adrenalin, glucagon, cortisol, and growth hormone promote both an increased glucose production and a mobilization of fatty acid from adipose tissue [37, 49, 52]. In addition, gluconeogenesis maintains glucose homeostasis by synthesizing glucose from substrates like pyruvate. These changes may increase fuel supply to the skeletal muscle contraction during exercise and prevent hypoglycemia as a result of excessive utilization of glucose by the contracting muscles.

Physical exercise is a recommended treatment for patients with type II DM because it enhances the GLUT4 expression in trained skeletal muscle with a consequent increase in the glucose transport capacity [48]. This mechanism may explain the enhanced sensitivity to insulin observed in physically active DM patients [11, 13, 16, 22, 24, 26]. Increased mass in skeletal muscle, enhanced blood flow in muscle, greater density of insulin receptors, enhanced disposal of glucose in skeletal muscle, and a reduction in body fat could also contribute to this insulin sensitivity and improved glucose tolerance induced by physical training in DM patients [25, 49].

As mentioned above, the aim of exercise in type II diabetic patients is to induce acute and chronic physiological changes, which improve insulin sensitivity and glucose tolerance [11, 13, 22, 23, 24, 26]. To maintain glucose homeostasis, glucagon and adrenalin are released during acute exercise, which increases hepatic glucose production; simultaneously, the insulin secretion by pancreatic β cells is reduced [37, 40, 52]. Thus, an increase in glucose utilization during acute exercise is accompanied by an increase in hepatic glucose production, an improved insulin sensitivity enhancing the binding of insulin to sarcolemmal receptors, and an increased GLUT4 expression [15]. From a chronic perspective, the improvement in insulin sensitivity is positively correlated with the intensity of aerobic endurance training, which is in accordance with the fact that insulin resistance in type II diabetic patients is associated with diminished physical fitness [15]. Regular exercise, combined with dietary control training, leads to changes in body composition, namely, a reduction in body fat and an increase in muscle mass [9, 15]. This association of dietary control with physical training seems to improve the glycemic control better than exercise alone [9, 15], and this assumption offers an explanation to why obese subjects with type II DM, when compared to non-obese patients, show no beneficial effects in insulin sensitivity from training alone [36].

When patients with type II DM participate in physical training programs, metabolic control is improved, as evidenced for example by a decrease in serum triglyceride (TG) and very low density lipoprotein (VLDL) cholesterol and an increase in high density lipoprotein cholesterol at rest [2]. However, some studies have found that middle-aged subjects (age 40–54 years) who exercise regularly have a better response in metabolic control when compared to older subjects (age 57–61 years), perhaps due to different pretraining levels of metabolic control or to differences in the intensity of the training program or magnitude of chronic complications with advanced age [48].

Exercise programs for diabetic patients should consist of aerobic endurance exercise, which enhances cardiorespiratory fitness, muscular strength, and endurance, and modifies body composition. However, in patients with type II DM, this type of training together with resistance training, as opposed to aerobic training alone, seems to induce better positive adaptations of glucose control, insulin function, muscular strength, and exercise tolerance [29, 42]. Nevertheless, resistance exercise or exercise performed at high intensities should only be carried out by individuals without any DM-associated chronic complications, such as proliferative retinopathy or hypertension [2, 7, 14, 40].

To improve cardiovascular performance, the recommended frequency of exercise is between three and five sessions per week. Moreover, obese diabetic patients may need to participate in daily physical activity to maximize caloric expenditure for effective weight management. Normally, patients with type II DM are elderly, showing a decline in muscle mass associated with a reduction in metabolic function. Resistance training programs increase muscle strength and muscle mass. Patients, however, with blood glucose higher than 300 mg/dl, congestive heart failure, uncontrolled arrhythmias, severe valvular malfunction, or an aerobic capacity lower than five MET, are not allowed to perform this type of training [14, 15, 34, 40, 52].

Resistance training should be performed at low intensity [40–50% of 1 repetition maximum (RM)], with 10–15 repetitions for each muscle group and a 3:1 ratio of endurance/resistance sessions [15, 28]. Low intensity is suggested to avoid exaggerated blood pressure. In the same way, regular breathing during exertion can also prevent a severe rise in cardiac afterload. The type of weightlifting equipment that could be used depends on the patients’ preferences and abilities [28].

There are several safe forms of exercise such as walking, jogging, bicycling, and swimming, which allow patients to maximize their caloric expenditure and to improve physical fitness enjoyably and effectively. Long-term exercise programs are usually accompanied by a dropout rate of 90% of the initial participants after 1 year[15], while in short-term exercise programs, dropout rates range from 35–80% during the first 3–6 months [27]. Many reasons could contribute to refraining from maintenance of exercise, including lack of time, travel problems, expenses, and injury, but waning motivation seems to be the main cause [31]. Setting of personal goals for individuals is necessary, both for the DM patients and staff involved in the program, because both are equally important in providing encouragement to continue exercising. Even though participation in regular exercise programs may be low, a good strategy to maintain patients’ involvement in such programs can be enhanced by routine activities of daily living. Lifestyle modifications such as stair climbing instead of using an elevator, household tasks, and gardening can provide appropriate physical activity with increased calorie burning [15].

The prevalence of diabetes retinopathy appears to vary with the age of onset and duration of the disease. Retinopathy lesions could be divided into two large categories: simple and proliferative. Part of the 10–18% of patients with simple retinopathy will eventually progress to the proliferative form within a 10-year period. About half of patients with proliferative retinopathy will become blind within 5 years [8, 17]. Patients with active proliferative diabetes retinopathy, who perform strenuous exercise, may provoke a vitreous hemorrhage or a traction retinal detachment. Therefore, such patients should avoid anaerobic exercise and physical activity that involves straining or Valsalva maneuvers, as in weightlifting. Exercise must be low-impact such as swimming, walking, and stationary cycling [7].

Cardiovascular disease is a major cause of mortality in persons with diabetes. Approximately, 85% of mortality in patients with type II diabetes is due to ischemic heart diseases. Silent heart attacks can occur in patients with DM because an autonomic neuropathy can mask the symptom of chest pain usually associated with myocardial ischemia [8, 34]. Hypertension, dyslipidemia, smoking, a family history of coronary disease, and the presence of micro- or macroalbuminuria also constitute risk factors [7, 51]. Graded exercise testing should be performed before the prescription of a training program.

Blood pressure higher than 140/90 mmHg is a major risk factor for the development of cardiovascular diseases and microvascular complications that normally occur in over 60% of patients with type II diabetes. Hypertension is likely to be present as part of the metabolic syndrome. In general, physical exercise associated with a diet aimed at reduced sodium intake, reductions in bodyweight, avoidance of excessive alcohol consumption, and increasing activity levels have proven to be effective in reducing blood pressure [7, 14, 51]. Activities involving breath holding, such as heavy resistance training, should be avoided unless the patients have acquired a proper breathing technique during such an activity. When weightlifting, it is important to exhale during the most strenuous part of the exercise and to inhale during the least, so that excessive changes in blood pressure are less likely to occur.

The occurrence of dyslipidemia increases the risk factor of macrovascular diseases. In type II diabetes, dyslipidemia is characterized by enhanced plasma levels of triglyceride and also by decreased levels of high density lipoprotein (HDL). This profile is often called “diabetic dyslipidemia” [6]. Regular physical exercise can reduce the risk of developing a macrovascular disease by the improvement of the plasma lipid profile [10, 28]. In fact, regular exercise seems to be effective in reducing the level of triglycerides and VLDL, while increasing HDL. Within the lipid profile, LDL should be less than 130 mg/dl, TG less than 200 mg/dl, and HDL more than 45 mg/dl [21]. The favorable reduction of triglycerides and lipoprotein cholesterol in patients with type II diabetes accompanies weight loss.

Low-intensity exercise, at least five times per week, 1 h per session, and performed continuously during 1 year, can reduce bodyweight. Weight loss also leads to a decrease in insulin resistance [7, 51].

Platelet dysfunction associated with dyslipidemia reveals a pattern of coagulation factors that increases coagulation, while on the other hand, decreases thrombolysis. In this case, platelet dysfunction could favor atherosclerosis and vascular thrombosis. Impairment in plasma fibrinolytic activity and tissue plasminogen activator activity, when plasminogen activator inhibitor-1 activity is increased, induces both thrombosis and defective dissolution of a clot once formed. Platelets in type II diabetes patients adhere to the endothelium because of insufficient generation of prostacyclin (PGI2) and nitric oxide (NO) by the vascular endothelium. Consequently, vasoconstriction and platelet aggregation could occur more rapidly than in healthy people. Insulin, by sensitizing the platelet to PGI2, is a natural antagonist of platelet hyperactivity, and in addition, it enhances the endothelial generation of PGI2 and NO. Thus, defects in insulin action in diabetes create a disordered platelet activity. Aspirin can block thromboxan synthesis by acetylation of the platelet cyclooxygenase and may be used to prevent cardiovascular disease in diabetic and nondiabetic patients [3, 45].

Aerobic exercise and resistance exercise are recommended for diabetic patients and must be individually adjusted to the physiological and metabolic limitations of each patient. Regular physical exercise and strength training encourage positive adaptations in the control of blood glucose concentration, insulin action, muscular strength, and exercise tolerance in patients with type II diabetes. However, to produce beneficial effects, exercise must be performed at a low intensity and duration (40–60% VO₂ max for at least 150 min/week). Blood glucose should be monitored before and after exercise to prevent hypoglycemia. Fluid replacement is recommended before, during, and after exercise. On the other hand, before starting an exercise program, a medical examination is necessary to identify diabetes-related complications affecting cardiovascular function, which may be aggravated by an exercise program. Nevertheless, lifestyle modifications including diet control coupled with physical regular exercise are important for successfully achieving glycemic control.