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.
Keywords: 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.
© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.