Increased fibrinogen production in type 2 diabetic patients without detectable vascular complications: Correlation with plasma glucagon concentrations

Fibrinogen is a strong cardiovascular risk factor in the general population , and increased fibrinogen plasma concentrations have been reported in type 2 diabetic patients. However, the mechanisms leading to hyperfibrinogenemi a in type 2 diabetes are not known. It is also not known whether possible a lterations of fibrinogen turnover may precede clinical diabetic micro- and macrovascular complications and therefore potentially contribute to their o nset. To address these questions, fibrinogen production was determined in s ix male type 2 diabetic patients without detectable micro- and macrovascula r complications (age, 45 +/- 4 yr; body mass index, 27 +/- 0.9 kg/m(2)) and in seven nondiabetic matched controls using leucine isotope precursor-prod uct relationships. Plasma glucose (P < 0.001), insulin (P < 0.05), and gluc agon concentrations (P < 0.01) were increased in the patients. Diabetic pat ients also had increased plasma fibrinogen concentration (+similar to 50%; P < 0.01) and pool (+similar to 40%; P < 0.01) as well as fractional (+simi lar to 35%; P = 0.08) and absolute (+similar to 100%; P < 0.01) synthetic r ates. The plasma glucagon concentration was positively related (P < 0.005 o r less) to the fibrinogen concentration as well as to fractional and absolu te synthetic rates. Thus, fibrinogen production is markedly enhanced, and t his alteration is likely to determine the observed hyperfibrinogenemia in t ype 2 diabetic patients. Hyperglucagonemia may contribute to the increased fibrinogen production. These findings in normoalbuminuric patients without clinical complications support the hypothesis that increased fibrinogen pro duction and plasma concentrations may precede and possibly contribute to th e onset of clinical cardiovascular complications in type 2 diabetes.