Independent Influence of Age on Basal Insulin Secretion in Nondiabetic Humans

Glucose tolerance deteriorates with aging. To test whether age per se impairs basal beta-cell function, we analyzed retrospective clamp data from a large group (n = 957) of nondiabetic Europeans over the 18-85 yr age range (the European Group for the Study of Insulin Resistance database). In this cohort, the fasting posthepatic insulin delivery rate [IDR, obtained as the product of clamp-derived posthepatic insulin MCR and fasting plasma insulin concentration] was 8.9 (6.6) mU/min (median and interquartile range), and it gradually increased with age. In univariate association, IDR was positively related to body mass index (P < 0.0001), fasting plasma glucose (P < 0.01), and waist-to-hip ratio (P < 0.001), and negatively related to insulin sensitivity (P < 0.0001). After controlling for these factors in a multivariate model, IDR declined significantly with age (P < 0.0001). This intrinsic effect of age on IDR was similar in men and women, and it averaged 25% between 18-85 yr. In the same statistical model, insulin MCR (but not fasting plasma insulin concentration) showed a significant (P < 0.0001) inverse relation to age. We conclude that, in nondiabetic Caucasian subjects of either sex, senescence per se is associated with a progressive decline in both insulin clearance and basal insulin release.