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Insulin Resistance Is Associated with Increased Circulating Level of Thrombin-Activatable Fibrinolysis Inhibitor in Type 2 Diabetic Patients

The Third Department of Internal Medicine and the Department of Molecular Pathobiology, Mie University School of Medicine, Mie 514-8507, Japan

Address all correspondence and requests for reprints to: Esteban C. Gabazza, M.D., Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie 514 8507. E-mail: gabazza{at}clin.medic.mie-u.ac.jp

Abstract

Hypofibrinolysis is a common finding in patients with diabetes mellitus (DM) and obesity and a risk factor for the development of cardiovascular disease. Recently, a new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. The present study was undertaken to assess the activity and circulating level of TAFI and its relation to fibrinolytic function and obesity in patients with type 2 DM. Fifty-seven patients with type 2 DM (38 men, 19 women) were enrolled in this study. DM patients were categorized in age-matched obese [body mass index (BMI) 25] and nonobese (BMI < 25) groups. The plasma concentration and activity of TAFI were significantly (P < 0.05) higher in DM patients than in healthy controls. The plasma levels and activity of TAFI were significantly (P < 0.05) elevated in obese DM patients compared with nonobese DM and nonobese healthy subjects. RT-PCR demonstrated the expression of TAFI in human adipose tissue and in human endothelial cells. The plasma levels of TAFI were independently and significantly correlated with glucose intolerance (HbA_1c), with obesity (BMI, visceral fat area), and with an indicator of insulin resistance (glucose infusion rate). This study showed that increased circulating level of TAFI may be an important causative factor of hypofibrinolysis in patients with type 2 diabetes, obesity and insulin resistance.

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