Xuan Qiuhui, Ouyang Yang, Wang Yanfeng, Wu Liang, Li Huating, Luo Yuanyuan, Zhao Xinjie, Feng Disheng, Qin Wangshu, Hu Chunxiu, Zhou Lina, Liu Xinyu, Zou Haidong, Cai Chun, Wu Jiarui, Jia Weiping, Xu Guowang
CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China.
University of Chinese Academy of Sciences Beijing 100049 China.
Adv Sci (Weinh). 2020 Oct 1;7(22):2001714. doi: 10.1002/advs.202001714. eCollection 2020 Nov.
Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack of effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite biomarkers for DR diagnosis, a multiplatform-based metabolomics study is performed. In this study, a total of 905 subjects with diabetes without DR (NDR) and with DR at different clinical stages are recruited. Multiplatform metabolomics methods are used to characterize the serum metabolic profiles and to screen and validate the DR biomarkers. Based on the criteria < 0.05 and false-discovery rate < 0.05, 348 and 290 metabolites are significantly associated with the pathogenesis of DR and early-stage DR, respectively. The biomarker panel consisting of 12-hydroxyeicosatetraenoic acid (12-HETE) and 2-piperidone exhibited better diagnostic performance than hemoglobin A1c (HbA1c) in differentiating DR from diabetes, with AUCs of 0.946 versus 0.691 and 0.928 versus 0.648 in the discovery and validation sets, respectively. In addition, this panel showed higher sensitivity in early-stage DR detection than HbA1c. In conclusion, this multiplatform-based metabolomics study comprehensively revealed the metabolic dysregulation associated with DR onset and progression. The defined biomarker panel can be used for detection of DR and early-stage DR.
糖尿病视网膜病变（DR）是全球劳动年龄成年人视力丧失或失明的主要原因。缺乏用于DR的有效诊断生物标志物导致治疗效果不尽人意。为了确定用于DR诊断的潜在代谢物生物标志物，进行了一项基于多平台的代谢组学研究。在本研究中，共招募了905名患有糖尿病但无DR（NDR）以及处于不同临床阶段的DR患者。采用多平台代谢组学方法来表征血清代谢谱，并筛选和验证DR生物标志物。基于标准P < 0.05和错误发现率< 0.05，分别有348种和290种代谢物与DR和早期DR的发病机制显著相关。由12-羟基二十碳四烯酸（12-HETE）和2-哌啶酮组成的生物标志物组在区分DR与糖尿病方面表现出比糖化血红蛋白（HbA1c）更好的诊断性能，在发现集和验证集中的曲线下面积（AUC）分别为0.946对0.691以及0.928对0.648。此外，该生物标志物组在早期DR检测中显示出比HbA1c更高的灵敏度。总之，这项基于多平台的代谢组学研究全面揭示了与DR发生和发展相关的代谢失调。所确定的生物标志物组可用于DR和早期DR的检测。
