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Effect of Aging on Glucose Homeostasis

Accelerated deterioration of β-cell function in individuals with impaired glucose tolerance

¹ Department of Medicine, University of Rochester School of Medicine, Rochester, New York
² Department of Biostatistics & Computational Biology, University of Rochester School of Medicine, Rochester, New York
³ Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany
⁴ Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
⁵ Department of Endocrinology, Carl T. Hayden VA Medical Center, Phoenix, Arizona
⁶ Diabetes/Metabolism Unit, Henry Dunant Foundation, Athens, Greece
⁷ Department of Clinical Medicine, Faculdade de Medicina Botucatu, University of São Paulo State, São Paulo, Brazil

Address correspondence and reprint requests to John E. Gerich, MD, University of Rochester School of Medicine, 601 Elmwood Ave., Box MED/CRC, Rochester, NY 1464. E-mail: johngerich{at}compuserve.com

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 < 0.01). Insulin sensitivity was not independently correlated with age in either group. 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 indexes 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 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.

Abbreviations: HOMA, homeostasis model assessment • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • UKPDS, UK Prospective Diabetes Study

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