文献类型：期刊文献

英文题名：Metabolomic etiological insights into six diabetic complications: a large scale Mendelian randomization atlas with colocalization validation

作者：Su, Meng[1,2];Si, Xinlei[1];Tian, Limin[1,3]

第一作者：Su, Meng

通信作者：Tian, LM[1];Tian, LM[2]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Peoples R China;[2]Gansu Prov Hosp, Dept Ophthalmol, Lanzhou, Peoples R China;[3]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Geriatr Endocrinol, Chengdu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Peoples R China;[2]corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Geriatr Endocrinol, Chengdu, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

外文期刊名：ACTA DIABETOLOGICA

收录：;Scopus(收录号：2-s2.0-105020316248);WOS:【SCI-EXPANDED(收录号:WOS:001605203600001)】；

基金：Gansu Provincial Department of Education: Outstanding Graduate Students 'Innovation Star' Project 2025CXZX-918.

语种：英文

外文关键词：Mendelian randomization; Diabetic complications; Serum metabolites; Genetic colocalization; Causality; Biomarkers; Precision medicine

摘要：Background and objectiveDiabetic complications can significantly affect the quality of life and prognosis of patients with diabetes. This study employed a systematic approach to elucidate the causal relationship between serum metabolites and six prevalent diabetic complications using a Mendelian randomization (MR) strategy.MethodsSerum metabolite data were obtained from genome-wide association studies, and data on six diabetic complications were acquired from the FinnGen consortium. A two-sample MR approach was used to investigate the association between serum metabolites and common diabetic complications. Reverse MR analysis was conducted to investigate potential causal relationships between diabetic complications and serum metabolite levels. Sensitivity analyses were performed to evaluate the robustness of our findings. Analyses included inverse-variance-weighted, MR-Egger, linkage disequilibrium score regression, and colocalization approaches.ResultsWe identified 81 causal associations, highlighting the significance of serum metabolites in the context of diabetic complications. The results identified significant causal associations: Bilirubin degradation products were inversely linked to diabetic retinopathy, while androstane sulfate and N-succinyl-phenylalanine increased the risk of retinopathy. Caffeine metabolites and adenosine 5'-monophosphate-to-citrate ratios were positively associated with nephropathy. Reverse MR analysis confirmed unidirectional causality, and sensitivity tests ruled out pleiotropy. Colocalization analyses highlighted shared genetic loci, such as rs2991970, between metabolites and hypoglycemia.ConclusionThese findings elucidate metabolite-specific pathways underlying diabetic complications and propose novel biomarkers for risk stratification. The limitations of this study include its European-centric nature and the lack of stratified covariates. This study highlights the value of integrating genetic and metabolomic data to enhance precision medicine in diabetes management.