Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation.
Tissue factor (TF) is the primary initiator of blood coagulation. Circulating TF procoagulant activity (TF-PCA) is associated with blood cells and microparticles and is elevated in patients with type 2 diabetes mellitus. Combined hyperinsulinemia and hyperglycemia and to a lesser degree selective hyperinsulinemia for 24 hours in healthy volunteers increased circulating TF-PCA, monocyte TF surface expression and mRNA, plasma thrombin generation, and coagulation factors VII and VIII activities, suggesting that the coagulation system had been activated. In addition, platelet CD40L and platelet-monocyte aggregates increased, indicating platelet activation. Somatostatin abolished these changes. We conclude that hyperinsulinemia, but particularly the combination of hyperinsulinemia and hyperglycemia, creates a prothrombotic state and may, in addition, be proinflammatory and proatherogenic by virtue of the actions of CD40L and TF.
Boden
Guenther
G
Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Center, Temple University Hospital, 3401 N. Broad Street, Philadelphia, PA 19140, USA. bodengh@tuhs.temple.edu
Rao
A Koneti
AK
D001777:Blood Coagulation / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood*; D013004:Somatostatin / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism*
D013004:Somatostatin; D013925:Thromboplastin