title: Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men.
abstract: Patients with diabetes have an increased prevalence of premature atherosclerotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hyperinsulinemia in the pathogenesis of these changes are unknown. To examine the effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men were infused with glucose to maintain levels at 11.1 mmol/l (approximately 200 mg/dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men were infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, approximately 150 microU/ml) and with glucose to maintain levels at 5.6 mmol/l (approximately 100 mg/dl) (euglycemia-hyperinsulinemia group). Measured were plasma activated factor VII activity (FVIIa), FVII coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue factor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum glucose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsulinemia. Markers of thrombin generation rose transiently and inconsistently during hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pathway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activation was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosmolality. The elevations in plasma coagulation factors during hyperglycemia-hyperinsulinemia, characteristic of type 2 diabetes, may constitute a potential for enhanced thrombin generation and thrombosis when triggered by exposure of tissue factor, such as during arterial plaque rupture.
authors.affiliation: Division of Hematology and Thromboembolic Diseases, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania 19140, USA. koneti@astro.ocis.temple.edu
authors.forename: A K
authors.initials: AK
authors.lastname: Rao
authors.forename: V
authors.initials: V
authors.lastname: Chouhan
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Boden
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000502:physiology*; D005167:Factor VII / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000008:administration & dosage; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D007328:Insulin; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D005169:Factor VIII; D013925:Thromboplastin; D015942:Factor VIIa; D013917:Thrombin; D005947:Glucose