Effect of Aging on Glucose Homeostasis
Accelerated deterioration of β-cell function in individuals with impaired glucose tolerance
- Ervin Szoke, MD1,
- Muhammad Z. Shrayyef, MD1,
- Susan Messing, MS2,
- Hans J. Woerle, MD3,
- Timon W. van Haeften, MD4,
- Christian Meyer, MD5,
- Asimina Mitrakou, MD6,
- Walkyria Pimenta, MD7 and
- John E. Gerich, MD1
- 1Department of Medicine, University of Rochester School of Medicine, Rochester, New York
- 2Department of Biostatistics & Computational Biology, University of Rochester School of Medicine, Rochester, New York
- 3Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany
- 4Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
- 5Department of Endocrinology, Carl T. Hayden VA Medical Center, Phoenix, Arizona
- 6Diabetes/Metabolism Unit, Henry Dunant Foundation, Athens, Greece
- 7Department 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
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 (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.
- HOMA, homeostasis model assessment
- IGT, impaired glucose tolerance
- NGT, normal glucose tolerance
- UKPDS, UK Prospective Diabetes Study
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 14 December 2007. DOI: 10.2337/dc07-1443.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted December 7, 2007.
- Received July 25, 2007.
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