Wu Yujie, Luo Yue, Wu Huiping, Yang Mengjie, Jin Jiahui, Shan Xiaoou, Zheng Zhichao
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, P.R. China.
Department of Pediatric Endocrinology, The Second Affiliated Hospital and Yuying, Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, P.R. China.
Hormones (Athens). 2025 Jun 18. doi: 10.1007/s42000-025-00687-7.
This study investigates the causal relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) across different age groups using Mendelian randomization (MR). The research aims to clarify how T2DM influences BMD and whether BMD variations contribute to the risk of developing T2DM, focusing on age-specific effects.
We conducted a two-sample MR analysis using publicly available data from genome-wide association studies (GWAS). Data sources included T2DM and BMD datasets across various age cohorts.The methodology incorporated diverse MR techniques, such as inverse-variance weighting (IVW), MR-Egger, and weighted median, to enhance robustness and mitigate potential biases. Additionally, reverse MR was performed to explore whether BMD affects the susceptibility to T2DM.
Our findings show a positive association between T2DM and higher BMD in individuals aged 45 and older. No significant relationship was observed in younger age groups (0-45 years). The reverse MR analysis revealed no causal link between BMD and T2DM, except in the 45-60 age group in whom a weak association was noted.
T2DM has a protective effect on BMD in older individuals, highlighting the importance of considering age in the management of bone health in T2DM patients. Further research is needed to understand the underlying mechanisms and to explore the potential clinical implications of these findings.
本研究采用孟德尔随机化(MR)方法,调查不同年龄组中2型糖尿病(T2DM)与骨密度(BMD)之间的因果关系。该研究旨在阐明T2DM如何影响骨密度,以及骨密度变化是否会增加患T2DM的风险,重点关注年龄特异性效应。
我们使用来自全基因组关联研究(GWAS)的公开可用数据进行了两样本MR分析。数据来源包括不同年龄队列的T2DM和BMD数据集。该方法采用了多种MR技术,如逆方差加权(IVW)、MR-Egger和加权中位数,以增强稳健性并减轻潜在偏差。此外,还进行了反向MR分析,以探讨骨密度是否会影响患T2DM的易感性。
我们的研究结果表明,45岁及以上个体的T2DM与较高的骨密度呈正相关。在较年轻的年龄组(0-45岁)中未观察到显著关系。反向MR分析显示,骨密度与T2DM之间无因果关系,但在45-60岁年龄组中发现了微弱关联。
T2DM对老年人的骨密度具有保护作用,这突出了在T2DM患者的骨骼健康管理中考虑年龄因素的重要性。需要进一步研究以了解潜在机制,并探索这些发现的潜在临床意义。