Insulin Sensitivity, Insulinemia, and Coronary Artery Disease
The Insulin Resistance Atherosclerosis Study
- Marian Rewers, MD, PHD1,
- Daniel Zaccaro, MS2,
- Ralph D’Agostino, Jr., PHD2,
- Steven Haffner, MD, MPH3,
- Mohammed F. Saad, MD4,
- Joe V. Selby, MD, MPH5,
- Richard Bergman, PHD6,
- Peter Savage, MD7 and
- for the Insulin Resistance Atherosclerosis Study Investigators
- 1Barbara Davis Center, University of Colorado HSC, Denver, Colorado
- 2Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
- 3Department of Medicine, University of Texas HS, San Antonio, Texas
- 4Department of Medicine, University of California Los Angeles, Los Angeles, California
- 5Department of Physiology and Biophysics, University of Southern California, Los Angeles, California
- 6Kaiser Research Center, Northern California, Division of Research, Oakland, California
- 7Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland
- Address correspondence and reprint requests to Marian Rewers, MD, PhD, Barbara Davis Center, University of Colorado Health Sciences Center, B-140, 4200 E 9th Ave., Denver, CO 80262. E-mail: marian.rewers{at}uchsc.edu
Abstract
OBJECTIVE—The aim of this study was to evaluate whether low insulin sensitivity (Si) measured using a modified frequently sampled intravenous glucose tolerance test with minimal model analysis is associated with coronary artery disease (CAD) independent of other cardiovascular risk factors.
RESEARCH DESIGN AND METHODS—We studied 1,482 women and men, age 40–69 years old, African American (28%), Hispanic (34%), or non-Hispanic white (38%), with normal (45%), impaired (23%), or diabetic (32%) glucose tolerance. CAD defined as confirmed past myocardial infarction, coronary artery bypass graft, coronary angioplasty, or presence of a major Q-wave was found in 91 participants.
RESULTS—The odds ratio (OR) for CAD was greatest among individuals in the two lowest quintiles of Si (2.4, 95% CI 1.0–5.6 and 4.7, 2.1–10.7) compared with the highest Si quintile. After adjusting for demographic and cardiovascular risk factors, a decrement from the 75th to 25th percentile in Si was associated with a 56% increase in CAD (P = 0.028). Similar increments in fasting or 2-h insulin levels were associated with, respectively, only 15 (NS) and 3% (NS) increases in CAD. The association between Si and CAD was partially mediated by insulin, HDL cholesterol and triglyceride levels, hypertension, diabetes, and obesity, but not LDL cholesterol or cigarette smoking.
CONCLUSIONS—Low Si is associated with CAD independently of and stronger than plasma insulin levels. Part of the association is accounted for by dyslipidemia, hypertension, diabetes, and obesity.
- CAD, coronary artery disease
- ECG, electrocardiogram
- FSIGT, frequently sampled intravenous glucose tolerance test
- HOMA, homeostasis model assessment
- IGT, impaired glucose tolerance
- IRAS, Insulin Resistance Atherosclerosis Study
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 December 1, 2003.
- Received September 1, 2003.
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