Porth's Essentials of Pathophysiology, 4e

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Diabetes Mellitus and the Metabolic Syndrome

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Although of benefit to people with diabetes, exer- cise must be weighed on the risk–benefit scale. Before beginning an exercise program, persons with diabe- tes should undergo an appropriate evaluation for macrovascular and microvascular disease. 30 The goal of exercise is safe participation in activities consis- tent with an individual’s lifestyle. As with nutrition guidelines, exercise recommendations need to be indi- vidualized. Considerations include the potential for hypoglycemia, hyperglycemia, ketosis, cardiovascular ischemia and arrhythmias (particularly silent isch- emic heart disease), exacerbation of proliferative reti- nopathy, and lower extremity injury. For those with chronic diabetes, the complications of vigorous exer- cise can be harmful and cause eye hemorrhage and other problems. Oral and Injectable Antidiabetic Agents Historically, two categories of antidiabetic agents existed: insulin injections and oral medications. However, this classification has been set aside since the introduc- tion of new injectable non-insulin antidiabetic agents. Because people with type 1 diabetes are deficient in insu- lin, they are in need of exogenous insulin replacement therapy from the start. People with type 2 diabetes can have increased hepatic glucose production, decreased peripheral utilization of glucose, decreased utilization of ingested carbohydrates, and, over time, impaired insulin secretion and excessive glucagon secretion from the pancreas (Fig. 33-8). The antidiabetic (non-insulin) agents used in the treatment of type 2 diabetes (insulin secretagogues, biguanides, α -glucosidase inhibitors, thi- azolidinediones, SGLT2 inhibitors, and incretin-based agents) attack each one of these areas and sometimes all. 31,32 If good glycemic control cannot be achieved with one or a combination of non-insulin agents, insulin can be added or used by itself. Insulin Secretagogues. The insulin secretagogues act at the level of the pancreatic beta cells to stimulate insu- lin secretion. There are two general classes of insulin secretagogues: (1) sulfonylureas and (2) meglitinides. 32 Both types require the presence of functioning beta cells, are used only in the treatment of type 2 diabetes, and have the potential for producing hypoglycemia. The control of insulin release from the pancreatic beta cells by glucose or the sulfonylurea drugs requires the generation of adenosine triphosphate (ATP), closing of an ATP-gated potassium channel, and opening of a transmembrane calcium channel. 32 The sulfonylureas (e.g., glipizide, glyburide, glimepiride) act by binding to a high-affinity sulfonylurea receptor on the beta cell that is linked to an ATP-sensitive potassium channel (Fig. 33-9). Binding of a sulfonylurea closes the channel, resulting in a coupled reaction that leads to an influx of calcium ions and insulin secretion. Because the sul- fonylureas increase insulin levels and the rate at which glucose is removed from the blood, it is important to recognize that they can cause hypoglycemic reactions. This problem is more common in elderly people with

The diabetic diet has undergone marked changes over the years, particularly in the recommendations for distribution of calories among carbohydrates, proteins, and fats. There no longer is a generic diabetic or ADA diet, but rather an individualized dietary prescription based on metabolic parameters, medical history of fac- tors such as renal impairment and gastrointestinal auto- nomic neuropathy, and treatment goals. For a person with type 1 diabetes, eating consistent amounts and types of food at specific and routine times is encour- aged. Home blood glucose monitoring is used to fine- tune the plan. Most people with type 2 diabetes are overweight; thus nutrition therapy focuses on achieving glucose, lipid, and blood pressure goals, and weight loss if indicated. Mild to moderate weight loss (5% to 10% of total body weight) has been shown to improve diabe- tes control, even if desirable weight is not achieved. Exercise The benefits of exercise for anyone include increased cardiovascular fitness and psychological well-being. For many people with type 2 diabetes, the benefits of exer- cise include a decrease in body fat, better weight con- trol, and improvement in insulin sensitivity. 11,30 Exercise is so important in diabetes management that an indi- vidualized program of regular exercise usually is consid- ered an integral part of the therapeutic regimen for every diabetic. In general, sporadic exercise has only transient benefits; a regular program is necessary for cardiovascu- lar conditioning and to maintain a muscle–fat ratio that enhances peripheral insulin receptivity. In people with diabetes, the beneficial effects of exer- cise are accompanied by an increased risk of hypogly- cemia. Although muscle uptake of glucose increases significantly, the ability to maintain blood glucose lev- els is hampered by failure to suppress the absorption of injected insulin and activate the counterregulatory mechanisms that maintain blood glucose. Not only is there an inability to suppress insulin levels, but insulin absorption may also increase. This increased absorp- tion is more pronounced when insulin is injected into the subcutaneous tissue of the exercised muscle, but it occurs even when insulin is injected into other body areas. Even after exercise ceases, insulin’s lower- ing effect on blood glucose continues. In some people with type 1 diabetes, the symptoms of hypoglycemia occur several hours after cessation of exercise, perhaps because subsequent insulin doses (in people using mul- tiple daily insulin injections) are not adjusted to accom- modate the exercise-induced decrease in blood glucose. The cause of hypoglycemia in people who do not administer a subsequent insulin dose is unclear. It may be related to the fact that the liver and skeletal mus- cles increase their uptake of glucose after exercise as a means of replenishing their glycogen stores, or that the liver and skeletal muscles are more sensitive to insulin during this time. People with diabetes should be aware that delayed hypoglycemia can occur after exercise and that they may need to alter their diabetes medication dose, their carbohydrate intake, or both.