Impact of Differences in Fasting Glucose and Glucose Tolerance on the Hyperbolic Relationship Between Insulin Sensitivity and Insulin Responses
- Kristina M. Utzschneider, MD1,
- Ronald L. Prigeon, MD2,
- Darcy B. Carr, MD3,
- Rebecca L. Hull, PHD1,
- Jenny Tong, MD1,
- Jane B. Shofer, MS4,
- Barbara M. Retzlaff, RN1,
- Robert H. Knopp, MD1 and
- Steven E. Kahn, MB, CHB1
- 1Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and Harborview Medical Center, University of Washington, Seattle, Washington
- 2Geriatric Research, Education and Clinical Center, Baltimore VA Medical Center and Division of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland
- 3Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Washington, Seattle, Washington
- 4Rehabilitation, Research and Development Center, VA Puget Sound Health Care System, Seattle, Washington
- Address correspondence and reprint requests to Kristina M. Utzschneider, MD, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108. E-mail: kutzschn{at}u.washington.edu
Abstract
OBJECTIVE—To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance.
RESEARCH DESIGN AND METHODS—We studied 219 healthy subjects (88 male and 131 female subjects, aged 26–75 years) with fasting plasma glucose (FPG) <6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance.
RESULTS—Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG <5.56 mmol/l vs. IFG, FPG 5.56–6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P < 0.001) and was progressively more left shifted with decreasing Kg (P < 0.001), consistent with decreasing β-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state β-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si × AIRg) was calculated as a measure of β-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG.
CONCLUSIONS—The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in β-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
- AIRg, acute insulin response to glucose
- DI, disposition index
- FPG, fasting plasma glucose
- IFG, impaired fasting glucose
- NFG, normal fasting glucose
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted November 14, 2005.
- Received December 8, 2005.
- DIABETES CARE
