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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Type 2 Diabetes: An Atherothrombotic Syndrome

Author(s): E. J. Dunn and P. J. Grant

Volume 5, Issue 3, 2005

Page: [323 - 332] Pages: 10

DOI: 10.2174/1566524053766059

Price: $65

Abstract

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.

Keywords: cardiovascular disease (cvd), insulin resistant, pancreatic beta-cells, obesity, hypertension, highdensity lipoprotein (hdl) cholesterol, atherosclerotic plaque, pro-inflammatory, endothelial dysfunction, fibrinolysis


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