Liang Min, Wang Jun, Xie Chao, Yang Yan, Tian Jian Wei, Xue Yao Ming, Hou Fan Fan
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, National Clinical Center of Kidney Disease, Guangzhou, China.
J Diabetes. 2014 Sep;6(5):417-26. doi: 10.1111/1753-0407.12134. Epub 2014 Mar 27.
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.
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.
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.
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.
内皮功能障碍是2型糖尿病（T2D）心血管疾病的早期事件，可在蛋白尿出现之前发生。氧化应激已被发现在内皮功能障碍的发展中起关键作用。因此，我们假设血浆晚期氧化蛋白产物（AOPPs）增加，这是一类在氧化应激过程中产生的氧化的、含二酪氨酸的蛋白质化合物，可作为无蛋白尿的T2D患者内皮功能障碍的早期标志物。
我们对147例新诊断的T2D患者（112例无蛋白尿，35例有蛋白尿）和49例年龄匹配的健康对照者进行了横断面调查。采用血流介导的血管舒张功能（FMD）评估内皮依赖性血管舒张功能，并测定血浆可溶性细胞间黏附分子-1（sICAM-1）浓度以评估血管损伤。使用改良的分光光度法测量血浆AOPPs浓度。
与健康对照相比，T2D正常白蛋白尿患者的血浆AOPPs浓度显著升高。在该人群中，血浆AOPPs浓度与FMD和血浆sICAM-1浓度相关。多变量回归分析表明，血浆AOPPs升高是这些患者内皮血管舒张功能受损和sICAM-1升高的最强危险因素。在有蛋白尿的T2D患者中也观察到类似结果。
血浆AOPPs浓度升高是内皮功能障碍的独立危险因素，因此可能是糖尿病早期个体血管病变的早期标志物。
