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 coronary heart disease (CHD) in women with Type 2 diabetes mellitus (DM). Methods CHD status was assessed via standard history and resting electrocardiogram in 41 postmenopausal diabetic and 41 age‐ and body mass index‐matched normoglycaemic women recruited from a community‐based cohort. The following parameters were assessed: body composition by dual energy X‐ray absorptiometry, blood pressure, metabolic and lipoprotein profile and haemostatic factors. Results Diabetic women with CHD (n = 14) had greater insulin resistance, calculated 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 also 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 contrast, in normoglycaemic women the major risk factors for CHD were elevated cholesterol, apolipoprotein(a), apolipoprotein B and systolic blood pressure (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 with Type 2 DM. Therapeutic approaches that increase insulin sensitivity may serve to reduce CHD risk in this vulnerable group. Diabet. Med. 18, 476–482 (2001)