Peripheral Thyroid Hormone Sensitivity Mediates the Association Between Body Composition and Diabetes in Euthyroid Adults

IF 9.1 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-09-14 DOI:10.1002/jcsm.70061

Nanfang Yao, Lan Liu, Yuqi Jiang, Dongmei Wang, Qianyi Lu, Yi Zeng, Genfeng Yu, Qintao Ma, Peiyi Li, Lingling Liu, Jie Shen, Heng Wan

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Abstract

Background

Body composition parameters, including fat-to-muscle ratio (FMR) and appendicular skeletal muscle mass (ASM), are closely associated with metabolic diseases. However, the mediating role of peripheral thyroid hormone sensitivity, reflected by the free triiodothyronine-to-free thyroxine ratio (FT3/FT4 ratio), in these associations remains unclear in euthyroid individuals. The current study aimed to investigate the associations of FMR and ASM/BMI with diabetes and to explore the potential mediating role of FT3/FT4 ratio in these relationships among euthyroid Chinese adults.

Methods

This cross-sectional study enrolled the participants from 10 communities in Guangdong Province, China, from November 2021 to September 2022. Body composition was measured using bioelectrical impedance analysis (BIA). Diabetes was defined based on fasting plasma glucose, 2-h postload glucose or glycated haemoglobin (HbA1c). Associations of FMR and ASM adjusted for body mass index (ASM/BMI) with diabetes were assessed using multivariable logistic regression. Structural equation modelling was applied to evaluate the mediating effect of FT3/FT4 ratio.

Results

A total of 5089 participants (mean age = 46 years, SD = 12) were included in the final analysis, consisting of 1957 men (38.5%) and 3132 women (61.5%). Participants in the third tertile (T3) of FMR exhibited a 79% higher prevalence of diabetes compared to those in the first tertile (T1) (OR 1.79, 95% CI 1.27–2.54) (p < 0.05). Conversely, those in the T3 of ASM/BMI had a 56% lower prevalence of diabetes compared to participants in T1 (OR 0.44, 95% CI 0.31–0.64) (p < 0.05). Restricted cubic spline analysis confirmed linear associations for both FMR and ASM/BMI with diabetes (both p for overall < 0.001; p for non-linear > 0.05). FT3/FT4 ratio significantly mediated the association between ASM/BMI and diabetes, accounting for 4.6% of the total effect (p < 0.05), whereas no significant mediation was observed in the FMR–diabetes pathway (p > 0.05).

Conclusions

In euthyroid individuals, higher FMR and lower ASM/BMI were independently associated with increased diabetes prevalence. The inverse relationship between ASM/BMI and diabetes may be partially mediated by FT3/FT4 ratio, highlighting peripheral thyroid hormone sensitivity as a potential mechanistic biomarker linking ASM loss to glycaemic dysregulation in euthyroid individuals.

Abstract Image

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外周甲状腺激素敏感性介导体成分与甲状腺功能正常成人糖尿病的关系。

身体组成参数，包括脂肪与肌肉比（FMR）和阑尾骨骼肌质量（ASM），与代谢性疾病密切相关。然而，外周甲状腺激素敏感性（由游离三碘甲状腺原氨酸与游离甲状腺素比值（FT3/FT4比值）反映）在这些关联中的中介作用在甲状腺功能正常的个体中尚不清楚。本研究旨在探讨FMR和ASM/BMI与糖尿病的关系，并探讨FT3/FT4比值在甲状腺功能正常的中国成年人中可能的中介作用。方法本横断面研究于2021年11月至2022年9月在中国广东省的10个社区招募参与者。采用生物电阻抗分析法（BIA）测定体成分。糖尿病的定义基于空腹血糖、负荷后2小时血糖或糖化血红蛋白（HbA1c）。采用多变量logistic回归评估经体质指数（ASM/BMI）调整的FMR和ASM与糖尿病的关系。采用结构方程模型评价FT3/FT4比率的中介作用。结果共纳入5089人（平均年龄46岁，SD = 12），其中男性1957人（38.5%），女性3132人（61.5%）。FMR第三分位（T3）的参与者糖尿病患病率比第一分位高79% (T1) (OR 1.79, 95% CI 1.27-2.54) （p 0.05）。FT3/FT4比值显著介导了ASM/BMI与糖尿病的相关性，占总效应的4.6% （p 0.05）。结论在甲状腺功能正常的个体中，较高的FMR和较低的ASM/BMI与糖尿病患病率增加独立相关。ASM/BMI与糖尿病之间的负相关关系可能部分由FT3/FT4比率介导，这突出表明外周甲状腺激素敏感性是甲状腺功能正常个体中ASM丧失与血糖调节异常相关的潜在机制生物标志物。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.