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Endothelial Dysfunction in Type 2 Diabetes Mellitus

The main cause for mortality and the great morbidity in diabetes (DM) is atherosclerosis. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction by recognizing that the endothelium plays a fundamental role in the maintenance of blood fluidity, vessel wall tone and permeability, the endothelium-derived nitric oxide (e-NO) being the main protector against atherosclerotic disease by inhibiting key pathways involved in atherogenesis. Endothelial dysfunction identified as an early marker of cardiovascular disease (CVD) could predict coronary artery disease in the future before the development of evident atherosclerotic changes in the arteries. Thus, the evaluation of endothelial function would identify subjects at high risk for CVD, such as determining flow-mediated endothelium-dependent vasodilatation, following induced ischemia, which requires the production of e-NO. Furthermore, it could also be assessed the vascular reactivity of the microcirculation as well as the biochemical markers of endothelial activity. Finally, it could also be measured the thickness of intima-media of large arteries, such as the carotids, an indirect measurement of the endothelial function. Endothelial dysfunction has been documented in DM, in individuals with insulin resistance or at high risk for future development of type 2 DM. In the DM subjects the hyperglycemia is associated with increased oxidative stress leading to increased formation of oxygen radicals such as super-oxide, which reacts with NO, causing it to be degraded. Although the diabetic state in type 1 DM predisposes to endothelial dysfunction it is not sufficient to cause it, other agents are likely to play a role. In type 2, the effects of aging, hyperelipidemia, hypertension and other factors add to the complexity of the problem and in contrast to the type 1 DM dysfunction, it could be observed years before the manifestation of the disease, associated with insulin resistance.

Type 2 diabetes; Type 1 diabetes; Endothelial dysfunction; Atherosclerosis; Nitric oxide; Oxidative stress; Insulin resistance


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