摘要
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 T1 DM.Although endothelial dysfunction(ED) precedes atherosclerosis,it is not clear weather,in recent onset T1 DM,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 T1 DM.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 T1 DM.
Macro and microvascular disease are the main causeof morbi-mortality in type 1 diabetes （T1DM）. Althoughthere is a clear association between endothelialdysfunction and atherosclerosis in type 2 diabetes, acause-effect relationship is less clear in T1DM. Althoughendothelial dysfunction （ED） precedes atherosclerosis,it is not clear weather, in recent onset T1DM, it mayprogress to clinical macrovascular disease. Moreover,endothelial dysfunction may either be reversedspontaneously or in response to intensive glycemiccontrol, long-term exercise training and use of statins.Acute, long-term and post-prandial hyperglycemiaas well as duration of diabetes and microalbuminuriaare all conditions associated with ED in T1DM. Thepathogenesis of endothelial dysfunction is closelyrelated to oxidative-stress. NAD（P）H oxidase overactivity induces excessive superoxide production insidethe mitochondrial oxidative chain of endothelial cells,thus reducing nitric oxide bioavailability and resultingin peroxynitrite formation, a potent oxidant agent.Moreover, oxidative stress also uncouples endothelialnitric oxide synthase, which becomes dysfunctional,inducing formation of superoxide. Other importantmechanisms are the activation of both the polyol andprotein kinase C pathways as well as the presence ofadvanced glycation end-products. Future studies areneeded to evaluate the potential clinical applicability ofendothelial dysfunction as a marker for early vascularcomplications in T1DM.
