Prospective associations of childhood metal mixtures with metabolic health in a Mexico City cohort

Background: Exposures to several metals and metalloids have been linked to impaired fasting glucose and insulin resistance that can progress to type 2 diabetes (T2D), which is increasing in prevalence among children and adolescents. However, the effects of metal mixtures on children’s metabolic health are less well characterized. We examined prospective associations of metals, individually and jointly, with metabolic parameters among children without T2D. Methods: We analyzed data from 422 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort (Mexico City, 2007–2011). Eleven metals (arsenic, cadmium, chromium, cesium, lead, antimony, cobalt, copper, manganese, selenium, zinc) were measured in whole blood at the age 4-year visit. Fasting plasma glucose was measured at the 4-, 6-, 8-, and 10-year visits. Fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were determined at the 8- and 10-year visits. Associations were estimated using generalized additive mixed models, linear mixed models, and quantile g-computation. Results: All metal–outcome associations were linear. Selenium was positively associated with average fasting plasma glucose, insulin, and HOMA-IR; zinc was negatively associated with insulin and HOMA-IR. A quartile increase in the metal mixture was associated with 1.10-fold higher insulin (95% confidence interval [CI] = 1.01, 1.21) and 1.11-fold higher HOMA-IR (95% CI = 1.01, 1.22), with the largest contributions from selenium and arsenic. Conclusion: Early childhood metals, particularly selenium, zinc, and arsenic, were prospectively associated with insulin resistance, consistent with findings in adults. More work is needed to understand how early-life metal mixture exposures may affect metabolic health.