Impaired glucose tolerance and insulin resistance are associated with hemostatic imbalance

Abstract

Impaired glucose tolerance (IGT) and insulin resistance (IR) are associated with elevated thrombosis risk, possibly via a disruption in hemostatic balance. PURPOSE: To investigate the association of IGT and IR with markers of blood coagulation and fibrinolysis. METHODS: Subjects were healthy nonsmoking sedentary men and post-menopausal women aged 50–75 years. An oral glucose tolerance test was used to assess fasting glucose and insulin concentrations, glucose and insulin areas under the curve (GAUC, IAUC), and IR by homeostatic model assessment (HOMA-IR). Hemostatic markers included plasma levels of prothrombin fragment, factor VIII antigen, factor VII antigen, tissue plasminogen activator (tPA) antigen, tPA activity, and plasminogen activator inhibitor-1 (PAI-1) activity. RESULTS: Fasting glucose correlated with tPA antigen and PAI-1 activity while fasting insulin correlated only with tPA activity. GAUC and IAUC were both correlated with PAI-1 activity, tPA activity, and tPA antigen. HOMA-IR correlated only with tPA antigen. No correlation was found with markers of blood coagulation. CONCLUSIONS: IGT and IR were associated with elevated anti-fibrinolytic activity (PAI-1 activity) and impaired fibrinolytic activity (tPA activity), but not with markers of coagulation. This implies that elevated risk of thrombosis with IGT and IR is due to impaired fibrinolysis.