中国全科医学2025，Vol.28Issue(21)：2625-2634,10.DOI:10.12114/j.issn.1007-9572.2023.0641
基于代谢组学探究非脂质代谢物在肥胖与糖尿病视网膜病变间的中介作用:孟德尔随机化研究
Metabolomics Based Mediating Role of Non-lipid Metabolites in the Relationship between Obesity and Diabetic Retinopathy:a Mendelian Randomization Study
摘要
Abstract
Background Obesity can influence the occurrence and progression of diabetic retinopathy(DR)through various pathways,however there are limited studies on the mediation of DR by obesity through non-lipid metabolic pathways.Objective To investigate the mediating role of non-lipid metabolites in the relationship between obesity and DR.Methods In August 2023,we utilized genome-wide association study(GWAS)data and conducted Mendelian randomization(MR)analysis to explore the mediating role of non-lipid metabolites in the association between obesity and DR.Results BMI(OR=1.78,P=5.3E-12)and waist-to-hip ratio(WHR)(OR=1.91,P=1.3E-10)was associated with increased risk of DR,respectively.Lower levels of isoleucine(OR=0.62,P=0.039),pyruvate(OR=0.60,P=0.039),albumin(OR=0.65,P=0.002),glycoprotein(OR=0.92,P=0.002),and decreased ratio of dienes to double bonds(OR=0.93,P=0.048)was associated with increased risk of DR,respectively.Positive causal associations were observed between BMI and isoleucine(OR=1.21,P=1.0E-08),glycoprotein(OR=1.33,P=3.2E-14),pyruvate(OR=1.08,P=0.03),and negative causal associations with albumin(OR=0.93,P=0.04)and the ratio of dienes to double bonds(OR=0.82,P=2.8E-05).Positive causal associations were also found between WHR and isoleucine(OR=1.34,P=3.4E-08)and glycoprotein(OR=1.26,P=1.2E-04).Isoleucine(β=-0.16,P=0.019),glycoprotein(β=-0.05,P=0.029),pyruvate(β=-0.07,P=0.027),and the ratio of dienes to double bonds(β=0.02,P=0.036)mediated the causal association between BMI and DR,while isoleucine(β=-0.21,P=7.2E-04)and glycoprotein(β=-0.03,P=0.031)mediated the causal association between WHR and DR.Conclusion Obesity has a positive causal association with DR,with BMI's association with DR mediated by isoleucine,glycoprotein,pyruvate,and the ratio of dienes to double bonds,and WHR's association with DR mediated by isoleucine and glycoprotein.Non-lipid metabolic products play a mediating role between obesity and DR.关键词
糖尿病视网膜病变/肥胖症/代谢组学/非脂质代谢物/体质指数/腰臀比/孟德尔随机化分析Key words
Diabetic retinopathy/Obesity/Metabolomics/Non-lipid metabolites/Body mass index,Waist-to-hip ratio/Mendelian randomization analysis分类
临床医学引用本文复制引用
王爽,吴树法,令垚,谭茜蔚,曹汝岱,曾慧婷,孔丹莉,丁元林,于海兵..基于代谢组学探究非脂质代谢物在肥胖与糖尿病视网膜病变间的中介作用:孟德尔随机化研究[J].中国全科医学,2025,28(21):2625-2634,10.基金项目
广东省基础与应用基础研究基金自然科学基金项目(2022A1515012407) （2022A1515012407）
广东省基础与应用基础研究基金区域联合基金项目(重点项目)(2020B1515120021) （重点项目）
广东省中医药科学技术研究项目(20221209) （20221209）
广东省医学科研基金项目(A2021395) （A2021395）
广东医科大学学科建设项目(4SG21276P) （4SG21276P）
广东医科大学本科教学质量和教学改革工程项目(1JG22125) （1JG22125）
东莞市科技特派员项目(20221800500342) （20221800500342）
东莞市社会发展科技项目(重点)(20221800905642) （重点）
大学生创新创业训练计划项目(S202210571088,GDMU2021112) （S202210571088,GDMU2021112）
