PHYSIOLOGICAL INHIBITORS OF BLOOD-COAGULATION AND PROTHROMBIN FRAGMENT F-1-2 DIABETIC-PATIENTS WITH NORMOALBUMINURIA AND INCIPIENT NEPHROPATHY(2 IN TYPE)

Microalbuminuria and haemostasis derangements have been considered as independent risk factors for cardiovascular death in type 2 (non-insul in-dependent) diabetic patients. Few studies have assessed coagulation inhibitors in type 2 diabetic patients with normoalbuminuria and micr oalbuminuria. Therefore, 32 type 2 diabetic patients with normoalbumin uria (albumin excretion rate, AER<20 mg/min, mean 7+/-1) and 28 type 2 diabetic patients with microalbuminuria (AER 20-200 mg/min, mean 84+/ -11) were studied. The patients were matched for age, sex, disease dur ation and treatment, body mass index (BMI), blood pressure and glycoha emoglobin. Protein C and S activity, antithrombin III, thrombomodulin and prothrombin fragments 1+2 (F 1+2) were assessed together with fibr inogen, triglycerides, total and high density lipoprotein (HDL)-choles terol concentrations. Fibrinogen, total and low density lipoprotein (L DL) concentrations were similar in the two groups, while a significant difference was observed for triglycerides (normoalbuminuric group: 12 8+/-10 mg/dl, microalbuminuric group: 184.1+/-17 mg/dl; P<0.007) and H DL-cholesterol (normoalbuminuric group: 45+/-2 mg/dl, microalbuminuric group: 39+/-2 mg/dl; P<0.05). The coagulation parameters were as foll ows: normoalbuminuric group: protein C activity 109%+/-5%, protein S 9 5.4%+/-5%, thrombomodulin 49.3+/-3 ng/ml, antithrombin III 93.3%+/-3%, F 1+2 1.05+/-0.04 nmol/l; microalbuminuric group: protein C activity 107%+/-4%, protein S 98.4%+/-4%, thrombomodulin 64.4+/-4 ng/ml, antith rombin III 93.3%+/-3%, F 1+2 1.03+/-0.05 nmol/l. The difference was si gnificant for thrombomodulin (P<0.007), A significant direct correlati on was observed in the microalbuminuric group between AER and thrombom odulin (r=0.38, P<0.05). In conclusion, our data do not support the hy pothesis that a reduction in the activity of anticoagulant physiologic al inhibitors (protein C, protein S, antithrombin III) could contribut e to explain the higher cardiovascular risk in type 2 diabetic patient s with microalbuminuria. The elevation of plasma thrombomodulin concen tration in type 2 diabetic patients could be the consequence of widesp read vascular damage in diabetic patients with incipient nephropathy.