Differential association of selenium exposure with insulin resistance and β-cell function in middle age and older adults

Abstract Objective To assess whether the role of selenium on pre-diabetes is differential by age, given comorbidities and decreased β-cell function in older adults. Research design and methods We evaluated the cross-sectional association of blood selenium with the homeostatic model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) in middle-aged (Aragon Workers Health Study [AWHS], N = 1186), and older (Seniors ENRICA [Study on Nutrition and Cardiovascular Risk in Spain]-2 [SEN-2], N = 915) diabetes-free adults. A subsample of participants from AWHS (N = 571) and SEN-2 (N = 603) had glucose and insulin repeated measurements for longitudinal analysis. We validated the cross-sectional dose–response associations in the 2011–2018 National Health and Nutrition Examination Survey (NHANES, N = 1317 middle age and N = 960 older) participants. Selenium was measured in whole blood with ICP-MS in AWHS, SEN-2 and NHANES. Results The cross-sectional geometric mean ratios (95% confidence intervals) per two-fold selenium increase were 1.09 (1.01, 1.19) for HOMA-IR and 1.15 (1.06, 1.24) for HOMA-β in AWHS; and 1.13 (0.98, 1.31) and 1.03 (0.90, 1.18), in SEN-2. The cross-sectional dose-response associations were consistent in NHANES, with mostly increasingly positive trends for both HOMA endpoints in younger adults and a plateau at levels >~150 μg/L in older adults. The longitudinal dose–response consistently showed positive associations at high selenium dose for both HOMA endpoints in the younger, but not the older, study population. Conclusions Increased blood selenium was associated with increased insulin resistance and β-cell function in middle-aged, but not in older individuals, especially for β-cell function. The results suggest that selenium-associated insulin resistance might induce compensatory increased β-cell function at younger ages, being this compensatory capacity decreased with aging.