Diabetes and Endothelial Dysfunction: A Clinical Perspective
Jorge Calles-Escandon and
Marilyn Cipolla
Departments of Internal Medicine (J.C.-E.) and Obstetrics and
Gynecology (M.C.), College of Medicine, University of Vermont,
Burlington, Vermont 05401
The main etiology for mortality and a great percent of morbidityin
patients with diabetes mellitus is atherosclerosis. A hypothesisfor
the initial lesion of atherosclerosis is endothelial dysfunction,
definedpragmatically as changes in the concentration of the chemical
messengersproduced by the endothelial cell and/or by blunting of the
nitricoxide-dependent vasodilatory response to acetylcholine or
hyperemia.Endothelial dysfunction has been documented in patients with
diabetesand in individuals with insulin resistance or at high risk for
developingtype 2 diabetes. Factors associated with endothelial
dysfunctionin diabetes include activation of protein kinase C,
overexpressionof growth factors and/or cytokines, and oxidative
stress. Severaltherapeutic interventions have been tested in clinical
trialsaimed at improving endothelial function in patients with
diabetes.Insulin sensitizers may have a beneficial effect in the short
term,but the virtual absence of trials with cardiovascular end-points
precludeany definitive conclusion. Two trials offer optimism that
treatmentwith ACE inhibitors may have a positive impact on the
progressionof atherosclerosis. Although widely used, the effect of
hypolipidemicagents on endothelial function in diabetes is not clear.
Therole of antioxidant therapy is controversial. No data
have beenpublished regarding the effects of hormonal replacement
therapyon endothelial dysfunction in postmenopausal women with type2
diabetes.
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