HEMOSTATIC ABNORMALITIES PERSIST DESPITE GLYCEMIC IMPROVEMENT BY INSULIN THERAPY IN LEAN TYPE-2 DIABETIC-PATIENTS

Diabetes mellitus is associated with disturbances of the haemostatic s ystem, which might contribute to the development of diabetic vascular disease. We investigated the effect of metabolic improvement by insuli n therapy on the haemostatic system in 61 patients with type 2 diabete s mellitus and secondary sulfonylurea failure compared with 45 healthy control subjects matched for age, sex and BMI. Median age was 65, med ian diabetes duration 10 years. Median HbA(1c) (10%) and fructosamine (4.0 mM) levels were elevated before induction of therapy and decrease d significantly within 6 months of insulin treatment to 7.5% and 3.0 m M, respectively (p <0.0001). Compared with control subjects, median pl asma levels of fibrinogen (317 vs 286 mg/dl), coagulation factor VII a ctivity (1.1 vs 0.89 U/l), von Willebrand factor(1.6 vs 1.3 U/l), D-di mer (105 vs 86 mu g/l), protein C:Ag (1.24 vs 0.95 U/l), total protein S:Ag (1.15 vs 0.91 U/l), and antithrombin m activity (1.17 vs 1.08 U/ l) were significantly elevated. Levels of free protein S were not diff erent from control values. No significant decline of coagulation param eters could be recorded during insulin therapy. Patients with diabetic vasculopathy had higher levels of D-dimer than those without (133 vs 76 mu g/l before, 109 vs 88 mu g/l during therapy), whereas the other haemostatic parameters were not different. Our data indicate a signifi cant activation of the coagulation system in diabetic patients with se condary failure to sulfonylurea drugs, with signs of a prethrombotic s tate and endothelial cell disturbance. Induction of insulin therapy re sults in a significant improvement of glycaemic and lipid metabolism, but the persisting enhanced activity state of the haemostatic system m ight contribute to the increased cardiovascular mortality of type 2 di abetic patients.