Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk

Objective. To investigate the relationship between variables of the coagulation and fibrinolysis system and insulin sensitivity in non-diabetic men at high and low risk of cardiovascular disease. Design. Cross-sectional study. Setting. Outpatient clinic in city hospital. Patients. Thirty-five men at high risk for atherosclerotic disease (hypertension and at least one the following factors: hypercholesterolaemia and smoking) and an age-matched low-risk group (n = 23) with no cardiovascular risk factors. Main outcome measures. Insulin-mediated glucose disposal (hyperinsulinaemic euglycaemic clamp) adjusted for lean body mass and fibrinogen, von Willebrand factor, prothrombin fragment 1 + 2, thrombin/antithrombin complex and plasminogen activator inhibitor activity were determined. Results. Insulin-mediated glucose disposal adjusted for lean body mass was significantly lower in the high-risk group than in the low-risk: group. Glucose disposal was significantly negatively associated with plasminogen activator inhibitor activity (PAI) in the high-risk group and with von Willebrand factor in the low-risk group. In the whole study group, fibrinogen and PAI were significantly associated with glucose disposal. After adjusting for confounding factors, glucose disposal was independently negatively associated with PAI in the high-risk group (P < 0.001) and in the whole group (P < 0.001). Conclusions. High-risk men were significantly more insulin-resistant than the low-risk group. Glucose disposal adjusted for lean body mass was associated with an impaired fibrinolytic activity in the high-risk group,Fibrinogen was associated with insulin resistance in the whole study group. The negative relationship between von Willebrand factor levels and glucose disposal in the low-risk group may indicate that insulin resistance can induce an endothelial dysfunction even in non-diabetic subjects.