ABSTRACT
Impaired fibrinolysis increases the risk of cardiovascular diseases and favors the intravascular deposition of fibrin. Fibrinolysis is regulated through plasminogen activators, and especially inhibitors, primarily the plasminogen activator inhibitor-l [PAI-l]. First-degree relatives of type 2 diabetic subjects are supposed to be genetically prone to the development of clinical disease. It might be possible that hemostatic dysregulalion may be present even in normal glucose tolerant first-degree relatives. In the present study, we aimed to investigate the hemostatic parameters, including tissue plasminogen activator [tPA], fibrinogen, PAI-l antigen, and PAI-l activity, in a group of diabetic patients offspring in comparison with healthy control subjects who have no family history of diabetes. We also investigated relationships between these parameters and plasma insulin levels. We studied 40 nondiabetic offspring of type 2 diabetic population. There were 25 normoglycemic subjects without a family history of diabetes who served as the control group. Fasting and post-load insulin concentrations were significantly higher in the offspring group compared with those in the control group. Plasma fibrinogen and LPA antigen concentrations were comparable between offspring and control subjects. Plasma PAI-l antigen concentration was higher in offspring compared with control subjects. Similarly, plasma PAI-l activity was significantly higher in offspring compared with control subjects. Plasma PAI-l activity was positively correlated with plasma PAI-l antigen and fibrinogen concentrations. PAI-l activity also had an inverse correlation with HDL cholesterol concentration, and was significantly correlated with the Waist Hip Ratio [WHR], plasma fibrinogen, plasma tPA antigen, and HDL cholesterol. These data suggest that none obese normal glucose tolerant offspring of type 2 diabetic subjects have elevated PAI-l activity indicating to hypofibrinolysis. Despite the presence of hyperinsulinemia and, possibly, insulin resistance, there is no association between insulin levels and PAI-l activity in these subjects. Hypofibrinolysis associated with enhanced PAI-l activity may be a risk factor for early development of atherosclerosis in these subjects who are genetically prone to the development of diabetes in the future. Large-scale controlled studies are required to elucidate whether the increased prevalence of cardiovascular diseases present even at the diagnosis of overt diabetes is related to hypofibrinolysis, in the prediabetic state