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

Abstract

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 or impaired glucose tolerance.

Research Design and Methods: First and second phase insulin secretion and insulin sensitivity were assessed in hyperglycemic clamp experiments in 266 individuals with normal glucose tolerance (NGT) and 130 individuals with impaired glucose tolerance (IGT), ranging in age from ∼20 to ∼70 years. Changes in beta 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<0.01). In neither group was insulin sensitivity independently correlated with age. In people with NGT, the Disposition Index for first and second phase insulin release decreased similarly at a rate of ∼0.7% per year. In people with IGT, the Disposition Indices for first and second phase insulin release decreased at greater rates (∼2.2 and 1.4% per year, 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 about 0.7% per year with aging; this decrease in beta 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.