Diabetes and endothelial dysfunction: A clinical perspective

The main etiology for mortality and a great percent of morbidity in patient s with diabetes mellitus is atherosclerosis. A hypothesis for the initial l esion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilat ory response to acetylcholine or hyperemia. Endothelial dysfunction has bee n documented in patients with diabetes and in individuals with insulin resi stance or at high risk for developing type 2 diabetes. Factors associated w ith endothelial dysfunction in diabetes include activation of protein kinas e C, overexpression of growth factors and/or cytokines, and oxidative stres s. Several therapeutic interventions have been tested in clinical trials ai med at improving endothelial function in patients with diabetes. Insulin se nsitizers may have a beneficial effect in the short term, but the virtual a bsence of trials with cardiovascular end-points preclude any definitive con clusion. Two trials offer optimism that treatment with ACE inhibitors may h ave a positive impact on the progression of atherosclerosis. Although widel y used, the effect of hypolipidemic agents on endothelial function in diabe tes is not clear. The role of antioxidant therapy is controversial. No data have been published regarding the effects of hormonal replacement therapy on endothelial dysfunction in postmenopausal women with type 2 diabetes.