Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis

The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secretory proteins, termed hepatokines. Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance. Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans. Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice. The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate-activated protein kinase (AMPK). In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes. Copyright © 2010 Elsevier Inc. All rights reserved.

The purpose of this study was to examine the relationship between serum selenium levels and the prevalence of diabetes among U.S. adults. We conducted a cross-sectional analysis of 8,876 adults > or =20 years of age who participated in the Third National Health and Nutrition Examination Survey. Diabetes was defined as the presence of a fasting plasma glucose > or =126 mg/dl, a self-report of a physician diagnosis of diabetes, or current use of insulin or oral hypoglycemic medication. Serum selenium was measured by atomic absorption spectrometry. Mean serum selenium levels in participants with and without diabetes were 126.5 and 125.7 ng/ml, respectively. Age-, sex-, race-, and BMI-adjusted mean selenium levels were 126.8 ng/ml in participants with diabetes and 124.7 ng/ml in participants without diabetes (adjusted difference 2.1 ng/ml [95% CI 0.4-3.8]; P = 0.02). The multivariable adjusted odds ratio for diabetes comparing the highest to the lowest quintile of serum selenium was 1.57 [1.16-2.13]. However, the association between high serum selenium and the prevalence of diabetes was nonlinear, with no clear trend in quintiles 2-4. In a probability sample of the U.S. population, high serum selenium levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, selenium intake, including selenium supplementation, should not be recommended for primary or secondary diabetes prevention in populations with adequate selenium status such as the U.S. population.

The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.