Insulin sensitivity, insulinemia, and coronary artery disease - The insulin resistance atherosclerosis study

OBJECTIVE- The aim of this study was to evaluate whether low insulin sensitivity (S;) 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.