Agerelated Changes In Glucose Metabolism

There is substantial evidence that age-related impairment in both insulin action and beta cell function are key factors in the high incidence of diabetes in the elderly (6,7). Typical changes in body composition, including an increase in overall adiposity, but especially visceral adipose tissue appear to be the major factors responsible for the resistance to insulin action (8). This effect is, at least in part, mediated by alterations in fat-derived peptides (adiponectin, TNF-alpha, leptin) and increased circulating free fatty acid levels (9). Reduction in skeletal muscle mass (sarcopenia) and infiltration of muscle tissue by fat may also contribute to impaired insulin-mediated glucose disposal (10). Defective inhibition of hepatic glucose production by insulin is an additional contributor to glucose intolerance with aging (11).

Insulin secretion in response to an oral glucose challenge, including reduction in both first and second phase insulin secretion (12,13), is characteristically impaired, even in normal aging. Similar alterations in insulin secretion following a mixed meal have also been reported (6) and suggest there is an intrinsic alteration in beta cell function. Beta cell mass may decline with age, but functional defects in insulin processing and exocytosis likely make a greater contribution to the age-related secretory defect. Hepatic insulin extraction is greater in the elderly and whole-body insulin clearance is lower, factors that reflect the complexity of changes in insulin and glucose metabolism with aging (6).

Additional factors contribute to the high rate of diabetes in the elderly, including medication use (glucocorticoids, thiazide diuretics, atypical anti-psychotics, etc.), sedentary lifestyle and dietary habits.

Age group

800,000 600,000

E 400,000 u

200,000 0

FIGURE 1 (A) Estimated total prevalence of diabetes in people aged 20 years or older by age group in the United States, 2005. (B) Estimated number of new cases of diagnosed diabetes in people aged 20 years or older by age group in the United States, 2005. Source: From Ref. 1.

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