Diabetes, Oxidative Stress, and Platelet Activation

Abstract

Diabetes mellitus is a major source of morbidity in developed countries and, among its comorbid conditions, atherosclerosis is perhaps the most important. Since the availability of insulin, up to three fourths of all deaths among diabetics can be directly attributed to coronary artery disease (CAD).1 In adult patients with diabetes, the risk of CAD is 3- to 5-fold greater in than nondiabetics despite controlling for other known CAD risk factors.1 In patients with IDDM, up to one third will die of CAD by the age of 50 years.2 A number of known risk factors for CAD, such as hypertension, central obesity, and dyslipidemia, are more common in diabetics than in the general population.1 Despite this prevalence of risk factors, no more than 25% of the excess CAD risk in diabetes can be accounted for by known risk factors.2 Thus diabetes represents a major contributing factor to the CAD burden in the developed world, and most of the excess attributed risk of CAD in diabetics cannot be readily quantified with the use of traditional risk factor analysis. Diabetes is associated with a variety of metabolic abnormalities, principle among which is hyperglycemia. The relation between hyperglycemia and CAD is the subject of considerable debate because serum glucose does not consistently predict the existence of CAD.2 Presumably, this confusion stems from the reliance on a single blood glucose measurement, as recent prospective data have clearly established a link between a marker for chronic average glucose levels (HbA1C) and cardiovascular morbidity and mortality.3 There is considerable controversy with respect to the precise mechanism by which hyperglycemia may contribute to the development of CAD in diabetes. Established sequelae of hyperglycemia, such as cytotoxicity, increased extracellular matrix production, and vascular dysfunction, have all been implicated in the pathogenesis …