Physiological inhibitors of blood coagulation and prothrombin fragment F 1+2 in type 2 diabetic patients with normoalbuminuria and incipient nephropathy

Microalbuminuria and haemostasis derangements have been considered as independent risk factors for cardiovascular death in type 2 (non-insulin-dependent) diabetic patients. Few studies have assessed coagulation inhibitors in type 2 diabetic patients with normoalbuminuria and microalbuminuria. Therefore, 32 type 2 diabetic patients with normoalbuminuria (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 duration and treatment, body mass index (BMI), blood pressure and glycohaemoglobin. Protein C and S activity, antithrombin III, thrombomodulin and prothrombin fragments 1+2 (F 1+2) were assessed together with fibrinogen, triglycerides, total and high density lipoprotein (HDL)-cholesterol concentrations. Fibrinogen, total and low density lipoprotein (LDL) concentrations were similar in the two groups, while a significant difference was observed for triglycerides (normoalbuminuric group: 128+/-10 mg/dl, microalbuminuric group: 184.1+/-17 mg/dl; P<0.007) and HDL-cholesterol (normoalbuminuric group: 45+/-2 mg/dl, microalbuminuric group: 39+/-2 mg/dl; P<0.05). The coagulation parameters were as follows: normoalbuminuric group: protein C activity 109%+/-5%, protein S 95.4%+/-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, antithrombin III 93.3%+/-3%, F 1+2 1.03+/-0.05 nmol/l. The difference was significant for thrombomodulin (P<0.007), A significant direct correlation was observed in the microalbuminuric group between AER and thrombomodulin (r=0.38, P<0.05). In conclusion, our data do not support the hypothesis that a reduction in the activity of anticoagulant physiological inhibitors (protein C, protein S, antithrombin III) could contribute to explain the higher cardiovascular risk in type 2 diabetic patients with microalbuminuria. The elevation of plasma thrombomodulin concentration in type 2 diabetic patients could be the consequence of widespread vascular damage in diabetic patients with incipient nephropathy.