Serum Manganese, Cobalt, Copper, Zinc, Selenium, and Iodine Levels, and the Incidence of Type 2 Diabetes: A Nested Case-control Study.

Although cross-sectional studies have shown that elevated serum manganese, cobalt, copper, zinc, selenium, and iodine are associated with a higher prevalence of type 2 diabetes, prospective evidence remains limited globally. This study aims to examine these associations in Japanese adults. A nested case-control study was performed in a cohort of 4754 health checkup examinees. During a 5-year follow-up, 325 cases of type 2 diabetes were identified by HbA1c, plasma glucose, or self-report. For each case, two controls were randomly matched for sex, age, and checkup date, resulting in 611 controls with measurements of serum trace elements. Serum trace elements were measured using triple quadrupole inductively coupled plasma mass spectrometry. Conditional logistic regression analysis was used to estimate the odds ratio of type 2 diabetes across quartiles of serum trace elements while adjusting for potential confounders. Compared with participants in the lowest quartile of serum manganese, those in the highest quartile had higher odds of type 2 diabetes (odds ratio: 1.95; 95% CI: 1.11, 3.41). Comparison of the highest and the lowest quartiles showed that higher serum zinc levels, albeit not statistically significant, were associated with a higher odds ratio for type 2 diabetes (odds ratio: 1.49; 95% CI: 0.93, 2.41). No association was found between each of the other elements and type 2 diabetes. Although manganese and zinc play a key role in glucose metabolism, our findings suggest that excessive circulating levels of these elements are associated with an increased incidence of type 2 diabetes.