Submitted to: New England Journal of Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2007
Publication Date: 6/1/2007
Citation: Stranges, S., Marshall, J.R., Natarajan, R., Donahue, R.P., Trevisan, M., Combs, G.F., Cappuccio, F.P., Ceriello, A., Reid, M.E. 2007. Effects of long-term selenium supplementation on the incidence of Type 2 diabetes. Annals of Internal Medicine. 147:217-223. Interpretive Summary: The manuscript reports the results of an analysis of a clinical trial previously conducted to determine whether daily supplements of selenium could reduce cancer risk. The present analysis evaluated the rates of type 2 diabetes diagnosed in that cohort over more than 7 years of intervention, finding that subjects treated with selenium had comparable rates of the disease as those treated with the placebo. This indicates that selenium supplementation, while effective in reducing cancer risk, did not affect the risk to developing type 2 diabetes.
Technical Abstract: Background: Oxidative stress is associated with insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus (DM). Observational studies have reported a protective role of dietary anti-oxidants in the development of type 2 DM. Moreover, findings from animal models suggest beneficial effects of supplements with the antioxidant selenium on glucose metabolism; however, data in humans are scanty. Methods: The authors examined the effect of a long-term selenium supplementation (200 µg daily) on type 2 DM incidence through the entire blinded phase of the Nutritional Prevention of Cancer Trial (1983-1996) among 1,250 participants who were free of type 2 DM at baseline (randomized to selenium: n = 621; randomized to placebo: n + 629). Results: During an average follow-up of 7.6 years, 100 total new cases of type 2 DM were accrued, 60 in the selenium group and 40 in the placebo group, for an incidence rate of 12.6 and 8.3 per 1,000 person years, respectively [hazard ration (HR) = 1.52, 95% confidence interval (CI) = 1.02-2.27]. The lack of benefits of selenium supplementation on the incidence of type 2 DM persisted when analyses were stratified by age, gender, body mass index, and smoking status. Moreover, an exposure-response gradient (P = 0.026) was found across tertiles of baseline plasma selenium concentrations, with a significantly increased risk of type 2 DM in the top tertile of baseline plasma selenium (HR = 2.55, 95% CI = 1.25-5.20). Conclusion: Overall, these findings indicate no effect of selenium supplementation on the prevention of type 2 DM in this population; moreover, the potential for adverse effects of long-term supplementation with selenium on glucose metabolism warrants further consideration.