Background: Increasing evidence suggests that high selenium levels are associated with diabetes and other cardiometabolic risk factors. \ud Objectives: We evaluated the association of serum selenium concentrations with fasting plasma glucose, glycosylated hemoglobin levels, and diabetes in the most recently available representative sample of the U.S. population. \ud Methods: We used a cross-sectional analysis of 917 adults ≥ 40 years of age who had a fasting morning blood sample in the National Health and Nutrition Examination Survey 2003–2004. We evaluated the association of serum selenium, measured by inductively coupled plasma-dynamic reaction cell-mass spectrometry, and diabetes, defined as a self-report of current use of hypoglycemic agents or insulin or as fasting plasma glucose ≥ 126 mg/dL. \ud Results: Mean serum selenium was 137.1 μg/L. The multivariable adjusted odds ratio [95% confidence interval (CI)] for diabetes comparing the highest quartile of serum selenium (≥ 147 μg/L) with the lowest (< 124 μg/L) was 7.64 (3.34–17.46). The corresponding average differences (95% CI) in fasting plasma glucose and glycosylated hemoglobin were 9.5 mg/dL (3.4–15.6 mg/dL) and 0.30% (0.14–0.46%), respectively. In spline regression models, the prevalence of diabetes as well as glucose and glycosylated hemoglobin levels increased with increasing selenium concentrations up to 160 μg/L. \ud Conclusions: In U.S. adults, high serum selenium concentrations were associated with higher prevalence of diabetes and higher fasting plasma glucose and glycosylated hemoglobin levels. Given high selenium intake in the U.S. population, further research is needed to determine the role of excess selenium levels in the development or the progression of diabetes
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