Marcello C Bertoluci, Marco V Wainstein, Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre RS 90035-003, Brazil.
World J Diabetes. 2015 Jun 10;6(5):679-92. doi: 10.4239/wjd.v6.i5.679.
Macro and microvascular disease are the main cause of morbi-mortality in type 1 diabetes (T1DM). Although there is a clear association between endothelial dysfunction and atherosclerosis in type 2 diabetes, a cause-effect relationship is less clear in T1DM. Although endothelial dysfunction (ED) precedes atherosclerosis, it is not clear weather, in recent onset T1DM, it may progress to clinical macrovascular disease. Moreover, endothelial dysfunction may either be reversed spontaneously or in response to intensive glycemic control, long-term exercise training and use of statins. Acute, long-term and post-prandial hyperglycemia as well as duration of diabetes and microalbuminuria are all conditions associated with ED in T1DM. The pathogenesis of endothelial dysfunction is closely related to oxidative-stress. NAD(P)H oxidase over activity induces excessive superoxide production inside the mitochondrial oxidative chain of endothelial cells, thus reducing nitric oxide bioavailability and resulting in peroxynitrite formation, a potent oxidant agent. Moreover, oxidative stress also uncouples endothelial nitric oxide synthase, which becomes dysfunctional, inducing formation of superoxide. Other important mechanisms are the activation of both the polyol and protein kinase C pathways as well as the presence of advanced glycation end-products. Future studies are needed to evaluate the potential clinical applicability of endothelial dysfunction as a marker for early vascular complications in T1DM.
大血管和微血管病变是 1 型糖尿病（T1DM）患者死亡和发病的主要原因。虽然 2 型糖尿病患者的内皮功能障碍与动脉粥样硬化之间存在明确的关联，但在 T1DM 中，因果关系尚不清楚。尽管内皮功能障碍（ED）先于动脉粥样硬化，但尚不清楚在近期发病的 T1DM 患者中，它是否会进展为临床大血管疾病。此外，内皮功能障碍可能会自发恢复，也可能对强化血糖控制、长期运动训练和使用他汀类药物有反应。急性、长期和餐后高血糖以及糖尿病病程和微量白蛋白尿的持续时间都是与 T1DM 中 ED 相关的条件。内皮功能障碍的发病机制与氧化应激密切相关。NAD（P）H 氧化酶过度活跃会导致内皮细胞线粒体氧化链内产生过多的超氧化物，从而降低一氧化氮的生物利用度并导致过氧亚硝酸盐的形成，而过氧亚硝酸盐是一种有效的氧化剂。此外，氧化应激还会使内皮型一氧化氮合酶解偶联，使其功能失调，导致超氧化物的形成。其他重要的机制包括多元醇和蛋白激酶 C 途径的激活以及晚期糖基化终产物的存在。需要进一步研究来评估内皮功能障碍作为 T1DM 早期血管并发症标志物的潜在临床应用价值。
