Type 2 diabetes: an atherothrombotic syndrome.
Insulin resistance is found in around 80-90% of subjects with older onset (type 2) diabetes and in approximately 25% of the general population. Insulin resistance prior to the development of frank type 2 diabetes and type 2 diabetes itself is associated with a significant increase in the risk of atherothrombotic disease, which is due in part to a disruption in the balance of factors regulating coagulation and fibrinolysis. Both insulin resistance and type 2 diabetes are associated with the development of endothelial dysfunction, and enhanced platelet aggregation and activation. Whilst the plasma levels of many clotting factors including fibrinogen, FVII, FVIII, FXII, FXIII b-subunit are elevated, the fibrinolytic system is relatively inhibited as a consequence of an increase in plasminogen activator inhibitor type-1 (PAI-1) levels. These changes favour the development of a hypercoagulable pro-thrombotic state, which may in turn enhance cardiovascular risk by increasing the likelihood of developing an occlusive thrombus within a coronary/cerebral artery, and/or contributing to the development of atherosclerotic lesions. This article reviews the current published evidence of the pro-thrombotic changes that occur in association with type 2 diabetes and insulin resistance, and the putative underlying mechanisms which lead to these changes.
Dunn
E J
EJ
Academic Unit of Molecular Vascular Medicine, Leeds Institute for Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, UK.
Grant
P J
PJ
D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005167:Factor VII / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D007333:Insulin Resistance; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013577:Syndrome; D013927:Thrombosis / Q000175:diagnosis* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D005167:Factor VII; D005169:Factor VIII; D005174:Factor XII; D005340:Fibrinogen; D005176:Factor XIII; D010959:Tissue Plasminogen Activator