High-density lipoprotein-cholesterol mediates the effects of testosterone-related hormons on type 2 diabetes mellitus: A two-step Mendelian randomization study
10.3760/cma.j.cn311282-20241112-00537
- VernacularTitle: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
- Author:
Xiaolin ZHAO
1
;
Naixin DOU
;
Yaqi GUO
;
Xinning WANG
;
Pengcheng CHEN
;
Chunxiao YU
;
Qingbo GUAN
Author Information
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
- Publication Type:Journal Article
- Keywords:
Total testosterone;
Bioavailable testosterone;
Diabetes mellitus, type 2;
High-density lipoprotein-cholesterol;
Mendelian randomization;
Male;
Female
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(2):111-119
- CountryChina
- Language:Chinese
-
Abstract:
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.
