Pathogenesis of Age-Associated Glucose Intolerance - Diabetes Mellitus - Geriatric Medicine
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Glucose intolerance associated with aging itself may predispose to the development of overt diabetes mellitus. Glucose intolerance is present even in very healthy older individuals. Postprandial blood glucose increases by 5.3 mg/dL per decade after the age of 30 (Figure 46.2). Age-related changes in fasting blood glucose levels are 1 to 2 mg/dL (0.05-0.09 mM) per decade after age 30.
Several factors appear to contribute to age-associated glucose homeostatic changes. Glucose absorption slows with increasing age, and hepatic glucose production shuts down after food and glucose is delayed, most likely as a result of delayed insulin secretion. Subtle age-related changes in regulation of insulin secretion have been described. The presence of insulin resistance in the elderly has been confirmed in multiple studies. It is a result of postreceptor events, the specific site(s) of which are not yet understood.
Other factors may contribute to glucose intolerance. Both the decline in lean body mass and the increase in body fat that accompany aging may contribute to insulin resistance. Reduced levels of physical activity and altered diet may cause these changes in body composition. Studies of master athletes suggest that some of these changes can be either prevented or modified with exercise. High-carbohydrate, low-fat diets improve insulin sensitivity in older individuals. Drugs commonly used by older individuals, including diuretics, tricyclic antidepressants, estrogen, sympathomimetics, glucocorti-coids, niacin, and phenytoin may adversely affect glucose metabolism. Stress states such as myocardial infarction, infection, burns, and surgery may also worsen glucose tolerance.
Impaired glucose tolerance is a risk factor for the development of cardiovascular disease and diabetes mellitus. The Honolulu Heart Study demonstrated that fatal myocardial events among older nondiabetic men were 2.4 times higher in those in the highest quintile for 1 h postchallenge glucose levels than in those in the lowest quintile. The risk of development of diabetes mellitus among those over age 70 who are glucose intolerant is 2% per year, as compared with a risk of 0.04% per year for those with normal glucose tolerance.
The reduction in glucose tolerance associated with aging is correlated with insulin resistance, obesity, hyperlipidemia, and hypertension. The pathogenesis of these associated and interrelated conditions is referred to as the metabolic syndrome or syndrome X. Although the pathogenesis is currently under detailed study, the emergence of insulin resistance as a central feature of diabetes mellitus in the elderly appears secure.
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