Margaret P. Rayman, Saverio Stranges

The potential of some selenoproteins to protect against oxidative stress led to the expectation that selenium would be protective against type 2 diabetes, and indeed in early in vivo and in vitro studies, selenium (as selenate) was shown to have antidiabetic and insulin-mimetic effects. However, more recently, findings from observational cross-sectional studies have raised concern that high selenium exposure may be associated with type 2 diabetes or insulin resistance, at least in well-nourished populations, though trial results have been inconsistent. Moreover, the largest trials that investigated the effects of selenium supplementation on diabetes endpoints have had cancer prevention as their primary outcome, casting doubt on the interpretation of posthoc analyses. Factors affecting serum/plasma selenium are not just location and level of disease-associated inflammation but the fact that higher concentrations of plasma selenoprotein P yet lower concentrations of glutathione peroxidase are found in type 2 diabetic patients than in normal subjects. From a public health perspective, selenium is marketed as a dietary supplement and is commonly added to multivitamin/mineral preparations that are consumed in many Western countries. Based on current evidence, however, the indiscriminate use of selenium supplements in individuals and populations with adequate-to-high selenium status cannot be justified and may increase risk. In conclusion, although there is a clear link between certain selenoproteins and glucose metabolism or insulin resistance, the relationship between selenium and type 2 diabetes is undoubtedly complex. It is possible that the relationship is U-shaped, with possible harm occurring both below and above the physiological range for optimal activity of some or all selenoproteins.