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Diabetes 52:1738-1748, 2003
© 2003 by the American Diabetes Association, Inc.

Mechanisms of the Age-Associated Deterioration in Glucose Tolerance

Contribution of Alterations in Insulin Secretion, Action, and Clearance

Rita Basu1, Elena Breda5, Ann L. Oberg2, Claudia C. Powell2, Chiara Dalla Man5, Ananda Basu1, Janet L. Vittone3, George G. Klee4, Puneet Arora1, Michael D. Jensen1, Gianna Toffolo5, Claudio Cobelli5, and Robert A. Rizza1

1 Endocrine Research Unit, Mayo Medical School, Rochester, Minnesota
2 Department of Health Service Research, Mayo Medical School, Rochester, Minnesota
3 Department of General Internal Medicine, Mayo Medical School, Rochester, Minnesota
4 Department of Laboratory Medicine & Pathology, Mayo Medical School, Rochester, Minnesota
5 Department of Information Engineering, University of Padua, Padua, Italy

Glucose tolerance decreases with age. For determining the cause of this decrease, 67 elderly and 21 young (70.1 ± 0.7 vs. 23.7 ± 0.8 years) participants ingested a mixed meal and received an intravenous injection of glucose. Fasting glucose and the glycemic response above basal were higher in the elderly than in the young participants after either meal ingestion (P < 0.001) or glucose injection (P < 0.01). Insulin action (Si), measured with the meal and intravenous glucose tolerance test models, was highly correlated (r = 0.72; P < 0.001) and lower (P ≤ 0.002) in the elderly than in the young participants. However, when adjusted for differences in percentage body fat and visceral fat, Si no longer differed between groups. When considered in light of the degree of insulin resistance, all indexes of insulin secretion were lower (P < 0.01) in the elderly participants, indicating impaired ß-cell function. Hepatic insulin clearance was increased (P < 0.002), whereas total insulin clearance was decreased (P < 0.002) in the elderly subjects. Multivariate analysis (r = 0.70; P < 0.001) indicated that indexes of insulin action (Si) and secretion (Phitotal) but not age, peak oxygen uptake, fasting glucose, degree of fatness, or hepatic insulin clearance predicted the postprandial glycemic response. We conclude that the deterioration in glucose tolerance that occurs in healthy elderly subjects is due to a decrease in both insulin secretion and action with the severity of the defect in insulin action being explained by the degree of fatness rather than age per se.

Address correspondence and reprint requests to Robert A. Rizza, MD, Mayo Clinic Rochester, 200 First St. SW, Rm. 5-194 Joseph, Rochester, MN 55905. E-mail: rizza.robert{at}mayo.edu


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