Body Selenium Status and Diabetes and Complications: The Multiphased Effect of Selenium.

Type 2 diabetes (T2D) is a growing public health issue. Although selenium (Se) is essential for physiological functions and health, its clear link to T2D and related diseases is not yet fully understood. The 2021 meta-analysis of observational studies indicated a positive association between Se and T2D. Current observational studies regarding Se and T2D have proliferated rapidly, particularly with new data emerging from China; this evidence needs to be re-searched and summarized. Furthermore, there is a lack of comprehensive reviews regarding Mendelian randomization (MR) studies and the association between Se and diabetes-associated complications. Thus, in this comprehensive review, which integrated narrative synthesis and meta-analyses, we reviewed the experimental, observational, MR studies, and randomized controlled trials (RCTs) of Se in T2D and related complications. The intricate association between Se and T2D and related diseases is discussed, as well as the limitations of the existing studies and the reasons for inconsistent results. A narrative review of experimental data finds that supranutritional Se intake/abnormal selenoprotein expression promotes the T2D-like phenotype. Meanwhile, updated random-effects meta-analyses of both observational trials and MR trials support that high-Se status increases the T2D. However, meta-analyses of RCTs have not supported that Se supplementation is harmful to the incidence of T2D. Moreover, there is growing evidence that high-Se status improves prognosis and reduces the risk of complications in individuals with T2D, such as diabetic cardiovascular disease, nephropathy, retinopathy, and foot ulcers. Similarly complex relationships have been observed in diabetes-related liver disease; a positive association was observed between Se and metabolic dysfunction-associated steatotic liver disease based on meta-analysis, yet Se appears to protect against liver fibrosis. These complex, multiphased effects in the relationship between Se and T2D and associated complications have increased the challenges of making more appropriate dietary recommendations to achieve the optimal concentration range for humans.