Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men

Patients with diabetes have an increased prevalence of premature atheroscle rotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hype rinsulinemia in the pathogenesis of these changes are unknown. To examine t he effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men mere infused with glucose to maintain levels at 11.1 mmol/l (similar to 200 mg/ dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men wer e infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, similar to 150 mu U/ml) and with glucose to ma intain levels at 5.6 mmol/l (similar to 100 mg/dl) (euglycemia-hyperinsulin emia group). Measured were plasma activated factor VII activity (FVIIa), FV II coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue fa ctor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum gluc ose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsuli nemia. Markers of thrombin generation rose transiently and inconsistently d uring hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pat hway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activat ion was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosm olality. The elevations in plasma coagulation factors during hyperglycemia- hyperinsulinemia, characteristic of type 2 diabetes, may constitute a poten tial for enhanced thrombin generation and thrombosis when triggered by expo sure of tissue factor, such as during arterial plaque rupture.