Type 2 Diabetes Mellitus

Type 2 Diabetes Defeated

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The effects produced by insulin, or any hormone, depend on the concentration of that hormone in the blood and on the sensitivity of the target tissue to given amounts of the hormone. Tissue responsiveness to insulin, for example, varies under normal conditions. Exercise increases insulin sensitivity and obesity decreases insulin sensitivity of the target tissues. The islets of a nondiabetic obese person must therefore secrete high amounts of insulin to maintain the blood glucose concentration in the normal range. Conversely, nondiabetic people who are thin and who exercise regularly require lower amounts of insulin to maintain the proper blood glucose concentration.

Type 2 diabetes is usually slow to develop, is hereditary, and occurs most often in people who are overweight. Genetic factors are very significant; people at highest risk are those who have both parents with type 2 diabetes and those who are members of certain ethnic groups, particularly Native Americans of the Southwestern United States and Mexican-Americans. Unlike people with type 1 diabetes, those who have type 2 diabetes can have normal or even elevated levels of insulin in their blood. Despite this, people with type 2 diabetes have hyperglycemia if untreated. This must mean that, even though the insulin levels may be in the normal range, the amount of insulin secreted is insufficient to control blood glucose levels.

Much evidence has been obtained to show that people with type 2 diabetes have an abnormally low tissue sensitivity to insulin, or an insulin resistance. This is true even if the person is not obese, but the problem is compounded by the decreased tissue sensitivity that accompanies obesity, particularly of the "apple-shape" variety in which the adipose cells are enlarged. There is also evidence that the beta cells are not functioning correctly: whatever amount of insulin they secrete is inadequate to the task. People who are prediabetic may have impaired glucose tolerance, which is defined (in an oral glucose tolerance test) as a plasma glucose level of 140 to 200 mg/dl at 2 hours following the glucose ingestion. As previously mentioned, a value here of over 200 mg/dl indicates diabetes. Since impaired glucose tolerance is accompanied by higher levels of insulin (fig. 19.12), a state of insulin resistance is suggested. People with chronic type 2 diabetes, in contrast, can have both insulin resistance and a deficient secretion of insulin.

Since obesity decreases insulin sensitivity, people who are genetically predisposed to insulin resistance may develop symptoms of diabetes when they gain weight. Conversely, this type of diabetes mellitus can usually be controlled by increasing tissue sensitivity to insulin through diet and exercise. This is beneficial

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■ Figure 19.12 Oral glucose tolerance in prediabetes and type 2 diabetes. The oral glucose tolerance test showing (a) blood glucose concentrations and (b) insulin values following the ingestion of a glucose solution. Values are shown for people who are normal, prediabetic, and type 2 (non-insulin-dependent) diabetic. Prediabetics (those who demonstrate "insulin resistance") often show impaired glucose tolerance without fasting hyperglycemia.

Data from Simeon I. Taylor et al., "Insulin Resistance of Insulin Deficiency: Which is the Primary Cause of NIDDM?" in Diabetes, vol. 43, June 1994, p. 735.

because exercise, like insulin, increases the amount of membrane GLUT4 carriers (for the facilitative diffusion of glucose) in skeletal muscle cells. If diet and exercise are insufficient, oral drugs are available that increase insulin secretion from the beta cells (e.g., sulfonylureas) and that decrease the insulin resistance of the target tissues. These are the thiazolidinediones discussed earlier (see page 606).

618 Chapter Nineteen

Clinical Investigation Clues

Remember that, according to the physician, Phyllis should diet and exercise. If that wasn't sufficient, she would have to take pills that he would prescribe for her.

What condition, does the physician believe, is producing Phyllis's symptoms?

How would diet and exercise help her? What pills might he prescribe?

Recent studies have demonstrated that, in most people with impaired glucose tolerance (who are prediabetic), the onset of type 2 diabetes can be prevented by changes in lifestyle. These changes include exercise and weight reduction, as previously mentioned, together with an increased intake of fiber, a reduced intake of total fat, and a reduced intake of saturated fat. In one recent study, these lifestyle changes decreased the risk of diabetes by 58% after 4 years.

People with type 2 diabetes do not usually develop ke-toacidosis. The hyperglycemia itself, however, can be dangerous on a long-term basis. In the United States, diabetes is the leading cause of blindness, kidney failure, and amputation of the lower extremities. People with diabetes frequently have circulatory problems that increase the tendency to develop gangrene and increase the risk for atherosclerosis. The causes of damage to the retina and lens of the eyes and to blood vessels are not well understood. It is believed, however, that these problems result from a long-term exposure to high blood glucose, which damages tissues through a variety of mechanisms.

4th Generation Hiv Test

Hours after oral glucose

■ Figure 19.13 Reactive hypoglycemia. An idealized oral glucose tolerance test on a person with reactive hypoglycemia. The blood glucose concentration falls below the normal range within 5 hours of glucose ingestion as a result of excessive insulin secretion.

performed. In the oral glucose tolerance test, for example, reactive hypoglycemia is shown when the initial rise in blood glucose produced by the ingestion of a glucose solution triggers excessive insulin secretion, so that the blood glucose levels fall below normal within 5 hours (fig. 19.13).

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