Huang Yu, Wen Jianxuan, Liao Xiaofeng, Chen Guiling, Zeng Xiang, Chen Yu
Laboratory of Stem Cell Clinical Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
The Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
J Diabetes Res. 2025 May 10;2025:6523642. doi: 10.1155/jdr/6523642. eCollection 2025.
This study is aimed at systematically investigating the potential causal impact of basal metabolic rate (BMR) on the risk of Type 2 diabetes (T2D). Data pertaining to single-nucleotide polymorphisms (SNPs) associated with BMR and T2D were gathered through a genome-wide association study (GWAS). Employing T2D as the dependent variable and BMR as the independent variable, SNPs displaying significant correlation with BMR were identified as instrumental variables (IVs). We also performed multivariable MR (MVMR) analyses using two different BMR datasets. The connection between BMR and the risk of T2D was scrutinized using the inverse-variance weighted (IVW) method, and a sensitivity analysis was executed to evaluate heterogeneity and pleiotropy. A potential causal relationship between higher BMR and increased T2D risk was observed (odds ratio (OR), 1.49; 95% confidence interval (CI), 1.31-1.7; < 0.001). Significant heterogeneity was identified (Cochran's test, < 0.001). However, sensitivity analyses demonstrated the robustness of the findings, with no evidence of horizontal pleiotropy and consistent results in leave-one-out tests. The MR-PRESSO test identified no outliers, confirming the absence of unknown pleiotropic effects. MVMR analyses, however, showed that the evidence became weaker after conditioning on BMI. Our study provides robust evidence of a causal link between higher BMR and increased T2D risk. Despite heterogeneity, sensitivity analyses support our findings, warranting further research to confirm results and explore underlying mechanisms.
本研究旨在系统调查基础代谢率（BMR）对2型糖尿病（T2D）风险的潜在因果影响。通过全基因组关联研究（GWAS）收集了与BMR和T2D相关的单核苷酸多态性（SNP）数据。以T2D为因变量，BMR为自变量，将与BMR显示出显著相关性的SNP确定为工具变量（IV）。我们还使用两个不同的BMR数据集进行了多变量孟德尔随机化（MVMR）分析。使用逆方差加权（IVW）方法研究了BMR与T2D风险之间的联系，并进行了敏感性分析以评估异质性和多效性。观察到较高的BMR与T2D风险增加之间存在潜在的因果关系（优势比（OR）为1.49；95%置信区间（CI）为1.31 - 1.7；P < 0.001）。确定存在显著的异质性（ Cochr an检验，P < 0.001）。然而，敏感性分析表明研究结果具有稳健性，没有水平多效性的证据，且在留一法检验中结果一致。MR - PRESSO检验未发现异常值，证实不存在未知的多效性影响。然而，MVMR分析表明，在对体重指数（BMI）进行校正后，证据变得更弱。我们的研究提供了有力证据，证明较高的BMR与T2D风险增加之间存在因果联系。尽管存在异质性，但敏感性分析支持我们的研究结果，有必要进行进一步研究以证实结果并探索潜在机制。
