高密度脂蛋白胆固醇参与睾酮相关激素对2型糖尿病的影响:一项两步孟德尔随机化研究  

High-density lipoprotein-cholesterol mediates the effects of testosterone-related hormons on type 2 diabetes mellitus:A two-step Mendelian randomization study

作　　者：赵筱琳 窦乃馨 郭雅琪 王馨宁 陈鹏程[2] 于春晓[1] 管庆波 Zhao Xiaolin;Dou Naixin;Guo Yaqi;Wang Xinning;Chen Pengcheng;Yu Chunxiao;Guan Qingbo(Key Laboratory of Endocrine Glucose&Lipids Metabolism and Brain Aging,Ministry of Education,Department of Endocrinology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China;Department of Endocrinology&Metabolism,Shanghai Fourth People′s Hospital,School of Medicine,Tongji University,Shanghai 200434,China)

机构地区：[1]内分泌糖脂代谢与脑老化教育部重点实验室,山东第一医科大学附属省立医院内分泌代谢病科,济南250021 [2]同济大学附属上海市第四人民医院内分泌科,上海200434

出　　处：《中华内分泌代谢杂志》2025年第2期111-119,共9页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金项目(82370849、82270839)。

摘　　要：目的探讨在不同性别中,睾酮相关激素与2型糖尿病(T2DM)因果关联的差异,并分析血脂在其中的中介作用。方法使用双样本MR(TSMR)、两步孟德尔随机化(MR)方法,在不同性别中探索睾酮相关激素与T2DM及血脂之间的因果关联,并使用多变量孟德尔随机化(MVMR)方法定量评估血脂在睾酮相关激素与T2DM之间潜在的介导作用。结果在男性中,总睾酮(TT)水平升高与T2DM患病率的降低相关(OR=0.90,95%CI 0.82~0.97,P=0.009),与高密度脂蛋白胆固醇(HDL-C)水平的升高相关(β=0.08 SD,95%CI 0.03~0.13,P=0.002)。在女性中,生物可利用睾酮(Bio-T)水平升高与T2DM患病率的升高相关(OR=1.24,95%CI 1.10~1.40,P<0.001),与HDL-C水平的降低相关(β=-0.13 SD,95%CI-0.21~-0.05,P<0.001)。中介分析发现,在女性中,HDL-C在Bio-T与T2DM之间起中介作用(中介比例7.83%)。在男性中,HDL-C在性激素结合球蛋白(SHBG)或TT与T2DM之间无中介效应,低密度脂蛋白胆固醇(LDL-C)在TT水平与T2DM之间无中介效应。结论男性TT和SHBG水平较低,女性Bio-T水平较高可能增加患T2DM的风险。在女性中,HDL-C在Bio-T与T2DM之间起中介作用,调控HDL-C或可能在防治与Bio-T紊乱相关的T2DM中发挥作用。Objective To investigate the gender differences in the causal relationship between testosterone-related hormones and type 2 diabetes mellitus(T2DM),and to analyze the mediating role of blood lipids in this relationship.Methods Using two-sample Mendelian randomization(TSMR)and two-step Mendelian randomization(MR)methods,we explored the causal associations between testosterone-related hormones,T2DM,and blood lipids in different genders.The potential mediating role of blood lipids between testosterone-related hormones and T2DM was quantitatively assessed using multivariate Mendelian Randomization(MVMR).Results In males,each standard deviation(SD)increase in genetically predicted total testosterone(TT)was associated with lower odds of T2DM(OR=0.90,95%CI 0.82-0.97,P=0.009)and higher high-density lipoprotein-cholesterol(HDL-C)level(β=0.08 SD,95%CI 0.03-0.13,P=0.002).In women,each SD rise in genetically predicted bioavailable testosterone(Bio-T)was associated with higher odds of T2DM(OR=1.24,95%CI 1.10-1.40,P<0.001),lower HDL-C level(β=-0.13 SD,95%CI-0.21--0.05,P<0.001).Mediation analysis revealed that HDL-C played a mediating role(7.83%)between Bio-T and T2DM in women.However,HDL-C showed no mediating effect between SHBG and TT levels on T2DM,and low-density lipoprotein-cholesterol(LDL-C)showed no mediating effect between TT levels on T2DM in men.Conclusions Lower levels of TT and SHBG in men,and high levels of Bio-T in women may increase the risk of T2DM.In women,regulating HDL-C levels may offer a potential strategy for the prevention and treatment of T2DM related to Bio-T disorders.

关 键 词：总睾酮 生物可利用睾酮 糖尿病 2型 高密度脂蛋白胆固醇 孟德尔随机化 男性 女性 

分 类 号：R587.1[医药卫生—内分泌]