基于代謝組學(xué)探究非脂質(zhì)代謝物在肥胖與糖尿病視網(wǎng)膜病變間的中介作用：孟德爾隨機化研究

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【關(guān)鍵詞】糖尿病視網(wǎng)膜病變；肥胖癥；代謝組學(xué)；非脂質(zhì)代謝物；體質(zhì)指數(shù)；腰臀比；孟德爾隨機化分析 【中圖分類號】R587.26【文獻標(biāo)識碼】A DOI：10.12114/j.issn.1007-9572.2023.0641

【Abstract】Background Obesity can influence the occurrence and progression of diabetic retinopathy（DR）throughvarious pathways，howevertherearelimitedstudiesonthemediationofDRbyobesitythrough non-lipid metabolicpathways.ObjectiveToinvestigate the mediatingroleofnon-lipid metabolites in therelationshipbetweenobesityand DRretinopathy：aMendelianrandomizationstudy[J].ChineseGeneralPractice，2O25，28（21）：2625-2634.°ledcirc Editorial Offce of Chinese General Practice.This is an open access article under the CC BY-NC-ND 4.0 license.MethodsIn August2023，weutilized genome-wideasociationstudy（GWAS）dataandconductedMendelianrandomization （MR）analysis to explore themediating roleofnon-lipid metabolites intheassociationbetweenobesityandDR.ResultsBMI （OR=1.78，P=5.3E-12）and waist-to-hip ratio （WHR）（ OR =1.91，P=1.3E-1O）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， （204 P =0.002），glycoprotein（OR=0.92， P =0.002），and decreased ratio of dienes to double bonds（OR=0.93， P =0.048） wasasociatedwith increasedriskofDR，respectivelyPositivecausalasociations wereobservedbetweenBMIandisoleucine （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）andtheratioof dienestodoublebonds（OR=0.82，P=2.8E-05）.Positive causal associationswere also found between WHR and isoleucine （ OR =1.34， P =3.4E-O8）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=O.O36）mediated the causal association between BMI and DR，while isoleucine （ β=-0.21 ，P=7.2E-O4）and glycoprotein（ β=-0.03 ，P=0.031）mediated the causal association between WHR and DR.ConclusionObesity has a positive causal association with DR，with BMI'sassociation with DR mediated by isoleucine，glycoprotein，pyruvate，and the ratioof dienes to double bonds，and WHR'sassciation with DR mediated by isoleucine and glycoprotein.Non-lipid metabolic products playamediating rolebetweenobesity and DR.

【Key Words】Diabetic retinopathy；Obesity；Metabolomics；Non-lipid metabolites；Body massindex，Waist-tohipratio;Mendelianrandomizationanalysis

糖尿病視網(wǎng)膜病變（diabeticretinopathy，DR）是糖尿病常見并發(fā)癥之一，也是導(dǎo)致全球范圍內(nèi)工作年齡段人群視力喪失的主要原因[1]。（剩余14570字）