The Causal Effect of Basal Metabolic Rate on Type 2 Diabetes: A Two-Sample Mendelian Randomization Study

Aim: This study is aimed at systematically investigating the potential causal impact of basal metabolic rate (BMR) on the risk of Type 2 diabetes (T2D). Methods: 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. Results: 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; p < 0.001). Significant heterogeneity was identified (Cochran's Q test, p < 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. Conclusion: 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.