Associations between urinary metals and metabolic syndrome, and the mediating role of systemic inflammation: Findings from a longitudinal study in rural China

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Although several studies have linked metal exposure to metabolic syndrome (MetS), prospective evidence for this association remains limited and inconclusive. Based on prospective data from rural Chinese adults, this study was designed to investigate the association of 22 urinary metals with MetS development and to assess whether systemic inflammation mediates this association. Modified Poisson regression and restricted cubic spline regression were applied to evaluate the relationships of urinary metal levels and systemic inflammation markers with MetS. Bayesian kernel machine regression (BKMR) was employed to estimate both the overall and single-metal impacts on MetS. Mediation analysis was further conducted to examine whether systemic inflammation acts as a mediator within the relationship between urinary metal levels and MetS. A total of 1227 participants were included, of whom 194 (15.81 %) developed MetS during follow-up (mean, 4.52 years). In the single-metal models, urinary manganese (Mn), zinc (Zn), and barium (Ba) exhibited positive dose-dependent relationships with MetS risk (all P-trend < 0.05). Compared with the lowest quartile, the RRs (95 % CIs) for MetS in the highest quartiles were 1.083 (1.030, 1.139) for Mn, 1.076 (1.026, 1.129) for Zn, and 1.082 (1.026, 1.142) for Ba. In the multi-metal models and the BKMR models, the positive correlations of urinary Mn, Zn, and Ba with MetS remained significant. BKMR analysis further revealed the interaction between urinary Zn and Ba. Mediation analysis showed that C-reactive protein (CRP) and lymphocyte count mediated 12.95 % and 7.85 % of the association of urinary Mn with MetS, respectively, while CRP and INFLA score explained 18.43 % and 10.56 % of the relationship between urinary Zn and MetS, respectively. White blood cell count, neutrophil count, and INFLA score exhibited negative mediating effects on the association between urinary Ba and MetS, with mediating ratios of - 7.14 %, - 5.23 %, and - 7.68 %, respectively. Our results indicate that elevated urinary Mn, Zn, and Ba levels are associated with increased MetS risk, potentially mediated by systemic inflammation.