State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Diabetes Metab Res Rev. 2024 Mar;40(3):e3789. doi: 10.1002/dmrr.3789.
Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD.
We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis.
The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered.
We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.
糖尿病肾病（DKD）是糖尿病的主要并发症之一，也是终末期肾病的主要原因。代谢组学可以提供疾病的独特代谢谱，从而预测或诊断疾病的发展。因此，本研究总结了更全面的一组与 DKD 相关的临床生物标志物，以确定与 DKD 发展显著相关的功能代谢物，并揭示其对 DKD 的驱动机制。
我们通过 2022 年 10 月检索了 PubMed、Embase、Cochrane 图书馆和 Web of Science 数据库。基于标准化均数差和均数比作为效应量的策略，对非靶向或靶向代谢组学研究数据进行了荟萃分析。我们比较了 DKD 患者和对照组之间代谢物水平的变化，并通过亚组分析、敏感性分析和荟萃回归分析探讨了异质性的来源。
34 项基于临床的代谢组学研究阐明了 DKD 和对照组之间的差异代谢物，其中包括 4503 名对照者和 1875 名 DKD 患者。结果表明，在这两项荟萃分析中总共发现了 60 种共同的差异代谢物，其中 5 种代谢物（p<0.05）被鉴定为必需代谢物。与对照组相比，DKD 患者中的甘氨酸、乌头酸、乙二醇酸和尿嘧啶显著降低；半胱氨酸显著升高。这表明 DKD 患者的氨基酸代谢、脂质代谢和嘧啶代谢紊乱。
我们已经确定了与 DKD 相关的 5 种代谢物和代谢途径，它们可以作为疾病预防和药物治疗的生物标志物或靶点。
