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

Abstract

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.