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Independent Influence of Age on Basal Insulin Secretion in Nondiabetic Humans

Consiglio Nazionale delle Ricerche Institute of Clinical Physiology (P.I.), 56126 Pisa, Italy

Address all correspondence and requests for reprints to: Patricia Iozzo, M.D., CNR Institute of Clinical Physiology, Via Savi, 8, 56126 Pisa, Italy. E-mail: pisamet{at}po.ifc.pi.cnr.it

Glucose tolerance deteriorates with aging. To test whether age per se impairs basal ß-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.

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