Insulin resistance as a major determinant of increased coronary heart disease risk in postmenopausal women with Type 2 diabetes mellitus

Aim To investigate the risk factors associated with clinically defined coro nary heart disease (CHD) in women with Type 2 diabetes mellitus (DM). Methods CHD status was assessed via standard history and resting electrocar diogram in 41 postmenopausal diabetic and 41 age- and body mass index-match ed normoglycaemic women recruited from a community-based cohort. The follow ing parameters were assessed: body composition by dual energy X-ray absorpt iometry, blood pressure, metabolic and lipoprotein profile and haemostatic factors. Results Diabetic women with CHD (n = 14) had greater insulin resistance, ca lculated by homeostasis model assessment (10.2 (7.0-14.8) vs. 6.5 (5.5-7.7) , P = 0.010), and higher plasminogen activator inhibitor-1 (PAI-1) levels ( 45 (29-69) vs. 24 (19-32) ng/ml, P = 0.013), than those without CHD. They a lso had higher triglycerides (2.9 (2.2-3.8) vs. 2.1 (1.8-2.4) mmol/l, P = 0 .016) and a trend towards reduced low-density lipoprotein particle size (25 .5 +/- 0.6 vs. 25.8 +/- 0.5 nm, P = 0.097). In a logistic regression model, insulin resistance was a significant independent predictor of CHD status ( odds ratio = 1.33, 95% confidence interval = 1.06-1.68, P = 0.015). In cont rast, in normoglycaemic women the major risk factors for CHD were elevated cholesterol, apolipoprotein(a), apolipoprotein B and systolic blood pressur e (P = 0.018, P = 0.016, P = 0.006 and P = 0.049, respectively). Conclusions Increased insulin resistance in association with elevated PAI-1 and dyslipidaemia appears to underpin the increased risk of CHD in women w ith Type 2 DM. Therapeutic approaches that increase insulin sensitivity may serve to reduce CHD risk in this vulnerable group.