Effect of Aging on Glucose Homeostasis: Accelerated Deterioration of Beta Cell Function in Individuals with Impaired Glucose Tolerance

OBJECTIVE —To examine the effect of aging on insulin secretion (first- and second-phase insulin release) and insulin sensitivity in people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS —First- and second-phase insulin secretion and insulin sensitivity were assessed in hyperglycemic clamp experiments in 266 individuals with NGT and 130 individuals with IGT, ranging in age from ∼20 to ∼70 years. Changes in β-cell function were compared using the disposition index to adjust for differences in insulin sensitivity. RESULTS —As expected, both phases of insulin release and insulin sensitivity were reduced in individuals with IGT (all P P = 0.002 and 0.009, respectively, vs. NGT), with the decrease in first phase being greater than that of second phase ( P = 0.025). CONCLUSIONS —Insulin secretion (both first and second phase) normally decreases at a rate of ∼0.7% per year with aging; this decrease in β-cell function is accelerated about two-fold in people with impaired glucose tolerance—first phase to a greater extent than second phase. Finally, aging per se has no effect on insulin sensitivity independent of changes in body composition.