Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes

Serum concentration of soluble thrombomodulin (TM) is thought to be a marke r for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagul ation and/or fibrinolysis system in patients with diabetes, we measured pla sma soluble TM, protein C activity (a natural anticoagulant induced by thro mbin-TM complex), prothrombin F1 + 2 (a direct marker of thrombin generatio n), and plasmin-alpha -2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The p lasma concentrations of soluble TM (P < 0.01), protein C activity (P < 0.01 ), prothrombin F1 + 2 (P < 0.05), PAP (P < 0.001) and D dimer (P < 0.001) w ere significantly higher in the diabetic patients than the 48 age-matched c ontrol subjects. The plasma concentrations of TM and PAP were obviously inc reased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the pro tein C activity (r = -0.43, P < 0.005), and were positively correlated with the plasma concentrations of prothrombin F1 + 2 (r = 0.63, P < 0.0001) and the plasma PAP concentrations (r = 0.30, P < 0.05). The present study demo nstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma c oncentration of soluble TM is associated not only with hypercoagulability b ut also with enhanced fibrinolysis in diabetic patients. (C) 2000 Elsevier Science B.V. All rights reserved.