脂肪分布与糖尿病肾脏病的因果关系以及胰岛素抵抗的中介作用:孟德尔随机化研究  

Causal effect of adipose distribution on diabetic nephropathy and mediating role of insulin resistance:A Mendelian randomization study

作　　者：张佳 李涵 罗彦相[1,2] 蔡青云 潘琦 Zhang Jia;Li Han;Luo Yanxiang;Cai Qingyun;Pan Qi(Department of Endocrinology,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China;Peking University Fifth School of Clinical Medicine,Beijing 100730,China;Graduate School of Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]北京医院内分泌科、国家老年医学中心、中国医学科学院老年医学研究院,北京100730 [2]北京大学第五临床医学院,北京100730 [3]中国医学科学院北京协和医学院研究生院,北京100730

出　　处：《中国医学前沿杂志(电子版)》2025年第1期42-48,共7页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：首都卫生发展科研专项(2024-1-4053)。

摘　　要：目的探究人体的不同脂肪分布,包括经体质量指数(body mass index,BMI)和身高调整的矫正BMI后的内脏脂肪分布量(BMI-adjusted visceral adipose tissue,VATadj),矫正BMI后的腹部皮下脂肪分布量(BMI-adjusted abdominal subcutaneous adipose tissue,ASATadj),矫正BMI后的臀股部脂肪分布量(BMI-adjusted gluteofemoral adipose tissue,GFATadj),与糖尿病肾脏病变(diabetic nephropathy,DN)之间的因果关联,以及胰岛素抵抗(insulin resistance,IR)的中介效应。方法使用公开的全基因关联研究(genome-wide association study,GWAS)的汇总水平数据,进行双样本孟德尔随机化(mendelian randomization,MR)和两步MR,其中逆方差加权法(inverse variance weighted,IVW)作为主要分析方法,加权中位数法和加权模式法作为补充方法。数据来源于英国生物样本库(UK biobank)、芬兰生物样本库(FinnGen)、葡萄糖和胰岛素相关性状元分析联盟荟萃分析。结果GFATadj与DN之间存在显著的因果关系(IVW:OR=0.668,95%CI:0.552~0.809,P=3.66×10^(-5)),其中IR介导了65.2%。IVW结果显示ASATadj与DN之间存在因果关联,但未在加权中位数和加权模式法中发现。未发现VATadj与DN之间的任何因果关联。结论GFATadj对DN产生因果效应,IR在GFATadj与DN之间起到中介作用。Objective To investigate the causal effect of fat distribution in the human body,including visceral adipose tissue(VAT),abdominal subcutaneous adipose tissue(ASAT),gluteofemoral adipose tissue(GFAT)on diabetic nephropathy(DN)and identify mediating role of insulin resistance(IR)in this association.Methods Two-sample mendelian randomization(MR)and two-step MR were performed using pooled level data from publicly available gene-wide association studies(GWAS)with inverse variance weighted(IVW)as the primary analysis method and weighted median and weighted mode methods as complementary methods.Data were obtained from UK biobank,FinnGen and Meta-Analysis of Glucose and Insulin-related Traits Consortium(MAGIC).Results There was a significant causal relationship between GFATadj and DN[odds ratio(OR)=0.668,95%confidence interval(CI)0.552-0.809,P=3.66×10^(-5)),with IR mediating 65.2%of this effect.A causal association between ASATadj and DN was observed in the IVW analysis,but no such association was found in the weight median and weight mode analyses.No causal association was found between VATadj and DN.Conclusions This MR study elucidated the causal impact of GFATadj on the subsequent risk of DN and identified IR as a mediator.

关 键 词：孟德尔随机化 脂肪分布 糖尿病肾脏病变 胰岛素抵抗 

分 类 号：R58[医药卫生—内分泌]