A systematic review and dose-response meta-analysis of exposure to environmental selenium and the risk of type 2 diabetes in nonexperimental studies

Accumulating evidence from both experimental and nonexperimental human studies in the last 15 years indicates that exposure to high levels of the trace element selenium increases the risk of type 2 diabetes. However, the relation of dose to effect is not well understood because randomized controlled trials used only one dose (200 mu g/day) of selenium supplementation. While no new trial on this topic has been published since 2018, several nonexperimental studies have appeared. We therefore updated a previous meta-analysis to include recently published observational studies, and incorporated the recently developed one-stage random-effects model to display the dose-response relation between selenium and type 2 diabetes. We retrieved 34 potentially eligible nonexperimental studies on selenium and diabetes risk up to April 15, 2021. The bulk of the evidence indicates a direct relation between blood, dietary and urinary levels of selenium and risk of diabetes, but not with nail selenium, which may be considered a less reliable biomarker. The association was nonlinear, with risk increasing above 80 mu g/day of dietary selenium. Whole blood/plasma/serum selenium concentrations of 160 mu g/L corresponded to a risk ratio of 1.96 (95% CI 1.27-3.03) compared with a concentration of 90 mu g/L (approximately 60 mu g of daily selenium intake). The cohort studies, which are less susceptible to reverse causation bias, indicated increased risk for both blood and urine selenium levels and dietary selenium intake, whereas no such pattern emerged from studies relying on nail selenium content. Overall, the nonexperimental studies agree with findings from randomized controlled trials, indicating that moderate to high levels of selenium exposure are associated with increased risk for type 2 diabetes.

Automated summary

Research indicates that high levels of selenium exposure increase the risk of type 2 diabetes, with uncertainty in the dose-effect relationship as only one dose (200 µg/day) was used in trials. Evidence suggests a direct link between blood, dietary, and urinary selenium levels and diabetes risk, with risk increasing above 80 µg/day of dietary selenium intake. Nonlinear associations were found, with higher whole blood/plasma/serum selenium concentrations correlating with increased risk ratios compared to lower concentrations.