Abstract
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.
Article PDF
Similar content being viewed by others
References and Recommended Reading
Pan WH, Cedres LB, Liu K, et al.: Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women. Am J Epidemiol 1986, 123:504–516.
Uusitupa MI, Niskanen LK, Siitonen O, et al.: 5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects. Circulation 1990, 82:27–36.
Kannel WB, D’Agostino RB, Wilson PW, et al.: Diabetes, fibrinogen and risk of cardiovascular disease: the Framingham experience. Am Heart J 1990, 120:672–676.
Laakso M, Lehto S: Epidemiology of macrovascular disease in diabetes. Diabetes Rev 1997, 5:294–315.
Virmani R, Kolodgie FD, Burke AP, et al.: Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Artherioscler Thromb Vasc Biol 2000, 20:1262–1275.
Osterman H, van de Loo J: Factors of the hemostatic system in diabetic patients. Haemostasis 1986, 16:386–416.
Kwaan HC: Changes in blood coagulation, platelet function, and plasminogen-plasmin system in diabetes. Diabetes 1992, 41(suppl 2):32–35.
Kario K, Mastuo T, Kobayashi H, et al.: Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients and microalbuminuria. Arterioscler Thromb Vasc Biol 1995, 15:1114–1120.
Morishita E, Asakura H, Jakaji H, et al.: Hypercoagulability and high lipoprotein (a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996, 120:7–14.
Jones RL: Fibrinopeptide-A in diabetes mellitus. Relation to levels of blood glucose, fibrinogen disappearance, and hemodynamic changes. Diabetes 1985, 34:836–843.
Ceriello A, Giugliano D, Quatraro A, et al.: Blood glucose may condition factor VII levels in diabetic and normal subjects. Diabetologia 1988, 31:889–891.
Rao AK, Chouhan V, Chen X, et al.: Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men. Diabetes 1999, 48:1156–1161.
Rauch U, Nemerson Y: Tissue factor, the blood, and the arterial wall. Trends Cardiovasc Med 2000, 10:139–143.
Mackman N: Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 2004, 24:1015–1022.
Wilcox JN, Smith KM, Schwartz SM, Gordon D.: Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A 1989, 86:2839–2843.
Giesen PLA, Rauch U, Bohrmann B, et al.: Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A 1999, 96:2311–2315.
Key NS, Slungaard A, Dandelet L, et al.: Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood 1998, 91:4216–4223.
Chou J, Mackman N, Merrill-Skoloff G, et al.: Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004, 104:3190–3197.
Vaidyula VR, Rao AK, Mozzoli M, et al.: Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor rocoagulant activity and platelet CD40 ligand. Diabetes 2006, 55:202–208.
Boden G, Vaidyula VR, Homko C, et al.: Differential effects of somatostatin on circulating tissue factor procoagulant activity and protein. Amer J Physiol Endocrinol Metab 2007, In press.
Peluso G, Petillo O, Melone MA, et al.: Modulation of cytokine production in activated human monocytes by somatostatin. Neuropeptides 1996, 30:443–451.
Niedermuhlbichler M, Wiedermann CJ: Suppression of superoxide release from human monocytes by somatostatin-related peptides. Regul Pept 1992, 41:39–47.
Vaidyula VR, Boden G, Rao AK: Platelet and monocyte activation of hyperglycemia and hyperinsulinemia in healthy subjects. Platelets 2006, 17:577–586.
Abdel-Hafiz E, Vaidyula VR, Bagga S, et al.: Elevated whole blood tissue factor procoagulant activity in diabetes mellitus. Vitamin E inhibits glucose induced tissue factor activity in vitro [abstract]. Blood 2002, 100:496a.
Sambola A, Osende J, Hathcock J, et al.: Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity. Circulation 2003, 107:973–977.
Johansson H, Lukinius A, Moberg L, et al.: Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes 2005, 54:1755–1762.
Moberg L, Johansson H, Lukinuis A, et al.: Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 2002, 360:2039–2045.
Peppelenbosch MP, Spek CA: Type I diabetes: a role for tissue factor in pancreatic islet transplantation? Lancet 2002, 360:1999–2000.
Shapiro AM, Lakey JR, Rajotte RV, et al.: Portal vein thrombosis after transplantation of partially purified pancreatic islets in a combined human liver/islet allograft. Transplantation 1995, 59:1060–1063.
Froberg MK, Leone JP, Jessurun J, Sutherland DE: Fatal disseminated intravascular coagulation after autologous islet transplantation. Hum Pathol 1997, 28:1295–1298.
Vaidyula VR, Abdel-Hafiz E, Bagga S, et al.: Inhibition of expression of tissue factor procoagulant activity by antiplatelet agents clopidogrel, aspirin and cilostazol in patients with peripheral arterial disease. Thromb Haemost 2006, 96:738–743.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Boden, G., Rao, A.K. Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation. Curr Diab Rep 7, 223–227 (2007). https://doi.org/10.1007/s11892-007-0035-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11892-007-0035-1