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Increased Fibrinogen Production in Type 2 Diabetic Patients without Detectable Vascular Complications: Correlation with Plasma Glucagon Concentrations

Departments of Clinical and Experimental Medicine (R.B., M.Z., G.D., E.K., A.T., P.T.) and Clinical and Laboratory Medicine (P.C.), University of Padova, 35128 Padova, Italy; and Department of Clinical Medicine and Endocrinology, University of Bari (P.T.), 70124 Bari, Italy

Address all correspondence and requests for reprints to: Prof. P. Tessari, Department of Clinical and Experimental Medicine, Policlinico, Via Giustiniani 2, 35128 Padova, Italy. E-mail: ptessari{at}ux1.unipd.it

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 hyperfibrinogenemia in type 2 diabetes are not known. It is also not known whether possible alterations of fibrinogen turnover may precede clinical diabetic micro- and macrovascular complications and therefore potentially contribute to their onset. To address these questions, fibrinogen production was determined in six male type 2 diabetic patients without detectable micro- and macrovascular complications (age, 45 ± 4 yr; body mass index, 27 ± 0.9 kg/m²) and in seven nondiabetic matched controls using leucine isotope precursor-product relationships. Plasma glucose (P < 0.001), insulin (P < 0.05), and glucagon concentrations (P < 0.01) were increased in the patients. Diabetic patients also had increased plasma fibrinogen concentration (+50%; P < 0.01) and pool (+40%; P < 0.01) as well as fractional (+35%; P = 0.08) and absolute (+100%; P < 0.01) synthetic rates. The plasma glucagon concentration was positively related (P < 0.005 or less) to the fibrinogen concentration as well as to fractional and absolute synthetic rates. Thus, fibrinogen production is markedly enhanced, and this alteration is likely to determine the observed hyperfibrinogenemia in type 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 production and plasma concentrations may precede and possibly contribute to the onset of clinical cardiovascular complications in type 2 diabetes.

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				R. Barazzoni, E. Kiwanuka, M. Zanetti, M. Cristini, M. Vettore, and P. Tessari Insulin Acutely Increases Fibrinogen Production in Individuals With Type 2 Diabetes but Not in Individuals Without Diabetes Diabetes, July 1, 2003; 52(7): 1851 - 1856. [Abstract] [Full Text] [PDF]