Prospective Association of High Dietary Selenium Intake with Increased Risk of Type 2 Diabetes in Women: The Ordet Cohort Study

Background: Growing evidence raises concern about possible associations of high selenium exposure with diabetes in the US, a population with high selenium status. In populations with lower selenium status, such as Italy, there is little data on the association of selenium with cardio-metabolic risk factors in the general population. We therefore examined the prospective association of dietary selenium intake with diabetes risk in the ORDET (HORmones and Diet in the ETiology of Breast Cancer) cohort study, a large sample of women from Northern Italy (n=7,182). Methods: Incident type 2 diabetes was defined as a self-report of a physician diagnosis, a self-report of use of antidiabetic medication, a prescription of antidiabetic medication by linkage with a regional prescription drug database, or a hospitalization discharge with a diabetes code by linkage with discharge records. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire. Participants were divided in quintiles based on their baseline dietary selenium intake. Results: Average selenium intake at baseline was 55.7 /day. After a median follow-up of 16 years, 253 women in the cohort developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of dietary selenium intake was 2.66 (95% CI: 1.48-4.75), with a significant linear trend (p = 0.001). The odds ratio for diabetes associated with an increase in selenium intake of 50 g/d was 3.63 (95% CI: 1.61-8.20). Conclusions: Increased dietary selenium intake was associated with a markedly increased risk of type 2 diabetes in a large sample of Italian women. Consistent with recent studies, these findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 g/day) with diabetes risk and sub-clinical metabolic toxicity.