[Endothelial dysfunction in patients with diabetes: identification, pathogenesis and treatment].
Cardiovascular diseases are the leading cause of morbidity and mortality in people with diabetes. Vascular abnormalities can be observed long before atherosclerosis develops and in sites not usually prone to atherosclerosis. These vascular abnormalities are known to be due to endothelial dysfunctions, one of the most frequent of which is depressed endothelium-dependent dilation. In patients with diabetes, this is mainly linked to decreased bioavailability of nitric oxide. Although inactivation of tetrahydrobiopterin, a co-factor of NO-synthase, may depress nitric oxide production, the latter is more likely due to the inactivation of nitric oxide by superoxide anions: enhanced oxidative stress increases their production in people with diabetes. Moreover, hyperglycemia directly activates oxidative stress, which in turn depresses endothelium-dependent vasodilation. Glycemia and oxidative stress are positively correlated in people with diabetes. However, while depression of endothelium-dependent dilation may be a visible functional manifestation of oxidative stress, the oxidative stress itself is mainly responsible for the cascade of endothelial events that play a key role in development of vascular atherosclerosis and its complications. Especially important among these events are the activation of NF-kappaB and the oxidation of LDL-cholesterol. Although antioxidants provide short-term improvement of endothelial function in humans, all studies of the effectiveness of preventive antioxidant therapy have been disappointing. Control of hyperglycemia thus remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes.
Nitenberg
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Service de physiologie et d'explorations fonctionnelles, Hôpital Jean Verdier, avenue du 14-Juillet, 93143 Bondy Cedex. alain.nitenberg@jvr.aphp.fr
D000975:Antioxidants; D001682:Biological Availability; D048909:Diabetes Complications / Q000503:physiopathology* / Q000628:therapy; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D009569:Nitric Oxide / Q000493:pharmacokinetics; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress
D000975:Antioxidants; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase