Increased plasma advanced oxidation protein products is an early marker of endothelial dysfunction in type 2 diabetes patients without albuminuria 血浆晚期蛋白氧化产物浓度升高是无白蛋白尿的2型糖尿病患者内皮细胞功能异常的早期标志物

• Published in: Journal of diabetes Vol. 6; no. 5; pp. 417 - 426
• Main Authors: Liang, Min, Wang, Jun, Xie, Chao, Yang, Yan, Tian, Jian Wei, Xue, Yao Ming, Hou, Fan Fan
• Format: Journal Article
• Language: English
• Published: Blackwell Publishing Ltd 01.09.2014
• Subjects: advanced oxidation protein products; endothelial dysfunction; normoalbuminuria; type 2 diabetes mellitus; 关键词：晚期蛋白氧化产物，内皮细胞功能异常，正常尿白蛋白，2型糖尿病
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/1753-0407.12134

Background Endothelial dysfunction is an early event of cardiovascular disease in type 2 diabetes (T2D) and can occur before albuminuria. Oxidative stress has been found to play a key role in the development of endothelial dysfunction. Therefore, we hypothesized that increases in plasma advanced oxidized protein products (AOPPs), a family of oxidized, dityrosine‐containing protein compounds generated during oxidative stress, could serve as an early marker of endothelial dysfunction in T2D patients without albuminuria. Methods We conducted a cross‐sectional investigation of 147 newly diagnosed T2D patients (112 without albuminuria and 35 with albuminuria) and 49 age‐matched healthy control subjects. Flow‐mediated vasodilation (FMD) was used to assess endothelium‐dependent vasodilator function, and plasma soluble intercellular adhesion molecule‐1 (sICAM‐1) concentrations were determined to evaluate vascular injury. Plasma AOPPs concentrations were measured using a modified spectrophotometric assay. Results Plasma AOPPs concentrations were significantly elevated in normoalbuminuric patients with T2D compared with healthy controls. Plasma AOPPs concentrations were correlated with FMD and plasma sICAM‐1 concentrations in this population. Multivariate regression analysis demonstrated that increased plasma AOPPs was the strongest risk factor for impaired endothelial vasodilation and increased sICAM‐1 in these patients. Similar results were observed in T2D patients with albuminuria. Conclusions Increased plasma AOPPs concentrations were an independent risk factor for endothelial dysfunction, and therefore may be an early marker of vasculopathy in individuals at an early stage of diabetes. 摘要 背景：内皮细胞功能异常是2型糖尿病患者心血管疾病的早期事件，其往往先于尿白蛋白增高而出现。氧化应激被认为是导致内皮细胞功能异常的关键机制。据此，我们提出以下假设：氧化应激过程中所生成的晚期蛋白氧化产物（advanced oxidized protein products，AOPPs）可作为一种早期生物学标志物，用于预测尿白蛋白水平正常的2型糖尿病患者是否存在内皮细胞功能异常。 方法：此研究共纳入了147名新诊断的2型糖尿病患者（112名尿白蛋白正常，35名有白蛋白尿）及49名年龄匹配的健康对照者。FMD被用于评估内皮细胞依赖的血管舒张功能，测定血浆细胞黏附因子（soluble intercellular adhesion molecule‐1，sICAM‐1）以评估血管损伤状况。采用修正的分光光度法测定血浆AOPP浓度。 结果：尿白蛋白水平正常的2型糖尿病患者其血浆AOPPs浓度较健康对照组显著升高。在此人群中血浆AOPPs浓度与FMD及血浆ICAM‐1浓度相关。多因素回归分析显示升高的血浆AOPPs浓度是与内皮舒张功能异常及血浆ICAM‐1水平升高关联最强的危险因素。同样的发现也在有白蛋白尿的2型糖尿病患者中得到证实。 结论：血浆AOPPs浓度升高是内皮细胞功能异常的独立危险因素，有望成为评估早期糖尿病患者血管病变的一个生物学标志物。