Guo Chengnan, Jiang Depeng, Xu Yixi, Peng Fang, Zhao Shuzhen, Li Huihui, Jin Dongzhen, Xu Xin, Xia Zhezheng, Che Mingzhu, Lai Mengyuan, Huang Ruogu, Wang Hui, Zheng Chao, Mao Guangyun
Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
Center on Evidence-Based Medicine and Clinical Epidemiological Research, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
Front Mol Biosci. 2022 Mar 17;9:822647. doi: 10.3389/fmolb.2022.822647. eCollection 2022.
Diabetic retinopathy (DR) is a major diabetes-related disease linked to metabolism. However, the cognition of metabolic pathway alterations in DR remains scarce. We aimed to corroborate alterations of metabolic pathways identified in prior studies and investigate novel metabolic dysregulations that may lead to new prevention and treatment strategies for DR. In this case-control study, we tested 613 serum metabolites in 69 pairs of type 2 diabetic patients (T2DM) with DR and propensity score-matched T2DM without DR ultra-performance liquid chromatography-tandem mass spectrometry system. Metabolic pathway dysregulation in DR was thoroughly investigated by metabolic pathway analysis, chemical similarity enrichment analysis (ChemRICH), and integrated pathway analysis. The associations of ChemRICH-screened key metabolites with DR were further estimated with restricted cubic spline analyses. A total of 89 differentially expressed metabolites were identified by paired univariate analysis and partial least squares discriminant analysis. We corroborated biosynthesis of unsaturated fatty acids, glycine, serine and threonine metabolism, glutamate and cysteine-related pathways, and nucleotide-related pathways were significantly perturbed in DR, which were identified in prior studies. We also found some novel metabolic alterations associated with DR, including the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives in DR. The results suggest that the metabolism disorder in DR can be better understood through integrating multiple biological knowledge databases. The progression of DR is associated with the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives.
糖尿病视网膜病变（DR）是一种与代谢相关的主要糖尿病并发症。然而，对于DR中代谢途径改变的认识仍然匮乏。我们旨在证实先前研究中确定的代谢途径改变，并研究可能导致DR新预防和治疗策略的新型代谢失调。在这项病例对照研究中，我们使用超高效液相色谱 - 串联质谱系统检测了69对患有DR的2型糖尿病患者（T2DM）和倾向评分匹配的无DR的T2DM患者的613种血清代谢物。通过代谢途径分析、化学相似性富集分析（ChemRICH）和综合途径分析对DR中的代谢途径失调进行了深入研究。通过受限立方样条分析进一步评估了ChemRICH筛选的关键代谢物与DR的关联。通过配对单变量分析和偏最小二乘判别分析共鉴定出了总计89种差异表达的代谢物。我们证实了不饱和脂肪酸的生物合成、甘氨酸、丝氨酸和苏氨酸代谢、谷氨酸和半胱氨酸相关途径以及核苷酸相关途径在DR中受到显著干扰，这些在先前的研究中已被确定。我们还发现了一些与DR相关的新型代谢改变，包括硫胺素代谢和色氨酸代谢的紊乱、海藻糖减少以及DR中胆碱和吲哚衍生物增加。结果表明，通过整合多个生物知识数据库可以更好地理解DR中的代谢紊乱。DR的进展与硫胺素代谢和色氨酸代谢的紊乱、海藻糖减少以及胆碱和吲哚衍生物增加有关。
