Association between type 2 diabetes-mediated obesity indicators and high-density lipoprotein cholesterol and non-alcoholic fatty liver disease:based on Mendelian randomization
ZHANG Jingjing
CHEN Hao
CHEN Xueqin
ZHANG Zhiyi
WANG Wenhao
CHEN Canjin
ZHOU Hao
DING Yuanlin
KONG Danli
Abstract：Objective To explore mediating role of type 2 diabetes mellitus(T2DM)in the association between non-alcoholic fatty liver disease(NAFLD)and its variables.Methods Applied univariate and multivariate Mendelian randomization analyses to explore the relationship between NAFLD and 46 variable factors and to investigate the role of T2DM in mediating this relationship.Results T2DM mediated the association of 7 variables,including high-density lipoprotein cholesterol and obesity assessment index(body mass index,waist circumference,arm fat mass,leg fat mass,total body fat mass,and trunk fat mass),with NAFLD,showing the most significant mediating effect for total body fat mass and NAFLD(mediating effect of 33.90%).Multivariate Mendelian randomization analysis after adjustment for body mass index showed that only high-density lipoprotein cholesterol remained associated with a reduced risk of NAFLD(P<0.05).Conclusion T2DM predominantly mediated the association between high-density lipoprotein cholesterol,obesity assessment metrics and NAFLD,whereas there was no significant causal relationship between other obesity assessment metrics,and NAFLD after adjustment for genetically predicted body mass index.High-density lipoprotein cholesterol may be a key protective factor for NAFLD.
Keywords：mendelian randomizationtype 2 diabetes mellitusnon-alcoholic fatty liver diseaseintermediary analysisvariable
Publication Date：2025-12-30
Online Publishing Date：2025-12-11(First online date of this platform, not the publication date of the document)
Pages：9( 613-621 )