Urinary metal exposure and type 2 diabetes mellitus: the potential mediating role of biological aging in older adults

Abstract The global burden of type 2 diabetes mellitus (T2DM) is increasing, and environmental exposures may contribute to diabetes susceptibility. Metals are widespread environmental contaminants associated with metabolic disorders; however, the role of aging-related processes in this association remains unclear. A total of 843 participants were enrolled. Urinary concentrations of six metals (Pb, Zn, Mn, Cr, As, and Co) were measured, and phenotypic age was calculated based on nine biomarkers. Multivariable logistic regression, restricted cubic spline models, weighted quantile sum regression, and exploratory mediation analysis were performed. Pb, Zn, Mn, and Cr exposures were significantly associated with increased T2DM risk (all P < 0.05). Mixed metal exposure was also associated with higher T2DM risk (OR = 1.515, 95% CI: 1.277–1.884). Additionally, Pb, Zn, Mn, and Cr were positively associated with phenotypic age, and each one-year increase in phenotypic age was associated with a 39.5% higher T2DM risk (OR = 1.395, 95% CI: 1.323–1.471). Phenotypic age may partially explain the associations between metal exposure and T2DM risk, with estimated mediation proportions of 10.9%–22.2%. Urinary metal exposure was associated with increased T2DM risk and higher phenotypic age. Phenotypic aging may represent a potential pathway linking environmental metal exposure with diabetes susceptibility.