Association of selenium with type 2 diabetes and obesity: A univariate and multivariate Mendelian randomization study

Selenium is associated with an increased risk of type 2 diabetes. However, whether the diabetogenic effect of selenium is mediated through increased body mass index (BMI) remains inconclusive. We conducted univariable and multivariable 2-sample Mendelian randomization (MR) to investigate the impact of selenium on the risk of type 2 diabetes and obesity. And further, we also tested whether the effect of selenium on diabetes was mediated through BMI. The inverse variance-weighted method was used as the main analysis to assess the effect estimates. Genetically proxied blood selenium (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.10-1.16, P < .001; per standard deviation elevation of selenium level) and toenail and blood selenium (OR 1.13, 95% CI 1.06-1.19, P < .001) were both associated with increased risk of type 2 diabetes. In multivariable MR analysis, the direct effect of selenium on the risk of type 2 diabetes decreased (blood selenium: OR 1.07, 95% CI 1.04-1.10, P < .001; toenail and blood selenium: OR 1.09, 95% CI 1.05-1.14, P < .001). The diabetogenic effect of selenium was mediated through increased BMI by 25% to 50%. This MR study suggests that the genetically proxied selenium is associated with increased risk of diabetes and obesity. And the diabetogenic effect of selenium is partially mediated through increased BMI.