Tao Sibei, Zheng Wen, Liu Yuan, Li Ling, Li Lingzhi, Ren Qian, Shi Min, Liu Jing, Jiang Jing, Ma Huichao, Huang Zhuo, Xia Zijing, Pan Jing, Wei Tiantian, Wang Yan, Li Peiyun, Lan Tian, Ma Liang, Fu Ping
Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University No. 37 Guoxue alley Chengdu 610041 China
West China-Washington Mitochondria and Metabolism Research Center, West China Hospital of Sichuan University Chengdu 610041 China.
RSC Adv. 2019 Jun 26;9(33):18713-18719. doi: 10.1039/c9ra01561b. eCollection 2019 Jun 14.
Type 2 diabetes mellitus (TDM) has a rising prevalence and diabetic nephropathy (DN) is a major complication of TDM. Metabolomics could provide novel insights into the pathogenesis, so we aimed to explore serum metabolomic profiles from DN to TDM. Serum samples were collected from 14 biopsy-proven DNs, 14 age/gender-matched TDMs without renal diseases (DM), 14 age/gender-matched healthy controls (CTRL) and household contacts of DM group (HH). Serum metabolomics was analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC/MS) assays. There were a total of 1470 metabolites identified from all serum samples. 45 metabolites with significantly different intensity were found between DN and DM, , biliverdin and taurine were reduced while l-arginine was increased in DN comparing to DM. DN could be distinguished from age/gender matched DM patients by l-arginine (AUC = 0.824) or taurine levels (AUC = 0.789). The metabolic pathways affected by metabolite distinctions between DN and DM also existed, among which taurine and hypotaurine metabolism exhibited the highest pathway impact. l-Methionine, deethylatrazine, l-tryptophan and fumaric acid were reduced in DM comparing with those of CTRL, but had no different intensity in DM and HH groups. The changes were demonstrated in the metabolomic profiles of biopsy-proven DN compared to DM. Biopsy-proven DN patients could be distinguished from age/gender matched DM by l-arginine or taurine levels in serum metabolomic profiles. Taurine and hypotaurine metabolism pathway had the highest impact in pathway set enrichment analysis, which potentially affected the pathogenesis of DN from TDM.
2型糖尿病（TDM）的患病率正在上升，而糖尿病肾病（DN）是TDM的主要并发症。代谢组学可以为发病机制提供新的见解，因此我们旨在探索从DN到TDM的血清代谢组学特征。从14例经活检证实的DN患者、14例年龄/性别匹配的无肾脏疾病的TDM患者（DM）、14例年龄/性别匹配的健康对照者（CTRL）以及DM组的家庭接触者（HH）中采集血清样本。通过非靶向液相色谱-串联质谱（LC/MS）分析进行血清代谢组学分析。从所有血清样本中共鉴定出1470种代谢物。在DN和DM之间发现了45种强度有显著差异的代谢物，与DM相比，DN中的胆红素和牛磺酸减少，而L-精氨酸增加。DN可以通过L-精氨酸（AUC = 0.824）或牛磺酸水平（AUC = 0.789）与年龄/性别匹配的DM患者区分开来。DN和DM之间代谢物差异所影响的代谢途径也存在，其中牛磺酸和亚牛磺酸代谢表现出最高的途径影响。与CTRL相比，DM中的L-蛋氨酸、去乙基莠去津、L-色氨酸和富马酸减少，但在DM和HH组中的强度没有差异。与DM相比，活检证实的DN的代谢组学特征有这些变化。活检证实的DN患者可以通过血清代谢组学特征中的L-精氨酸或牛磺酸水平与年龄/性别匹配的DM区分开来。在通路集富集分析中，牛磺酸和亚牛磺酸代谢途径影响最大，这可能影响了从TDM到DN的发病机制。
