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Insulin Sensitivity, Insulinemia, and Coronary Artery Disease

The Insulin Resistance Atherosclerosis Study

¹ Barbara Davis Center, University of Colorado HSC, Denver, Colorado
² Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
³ Department of Medicine, University of Texas HS, San Antonio, Texas
⁴ Department of Medicine, University of California Los Angeles, Los Angeles, California
⁵ Department of Physiology and Biophysics, University of Southern California, Los Angeles, California
⁶ Kaiser Research Center, Northern California, Division of Research, Oakland, California
⁷ Division 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

OBJECTIVE—The aim of this study was to evaluate whether low insulin sensitivity (S_i) 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 S_i (2.4, 95% CI 1.0–5.6 and 4.7, 2.1–10.7) compared with the highest S_i quintile. After adjusting for demographic and cardiovascular risk factors, a decrement from the 75th to 25th percentile in S_i 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 S_i 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 S_i 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.

Abbreviations: 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

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