Longitudinal Associations of Per- and Polyfluoroalkyl Substances with Metabolic Syndrome from Adolescence to Early Adulthood: A 10-Year Prospective Cohort Study.

Abstract

PER: and polyfluoroalkyl substances (PFAS) have been implicated in metabolic dysregulation; however, longitudinal evidence linking PFAS to metabolic syndrome (MS) across the transition from adolescence or young adulthood into early adulthood is still lacking. We analyzed 516 participants aged 12-30 years in the Young Taiwanese Cohort (YOTA) with baseline examinations in 2006-2008 and follow-up in 2017-2019. Eleven plasma PFAS and MS components were quantified at both time points. We used joint models that simultaneously included baseline PFAS and long-term PFAS changes to evaluate associations with follow-up MS and its components. A PFAS exposure index was derived as the mean of standardized ln-PFAS. The baseline PFAS exposure index was not associated with MS or its components. Among individual baseline PFAS, linear PFOA was inversely associated with impaired fasting glucose, and both linear PFOA and PFHxS were inversely associated with elevated blood pressure. In contrast, the PFAS exposure index change was inversely associated with follow-up MS (OR 0.36, q = 0.050) and follow-up MS waist (OR 0.22, q < 0.001). Among individual PFAS changes, follow-up MS was inversely associated with changes in linear PFOA, PFHxS, and PFDoA, and MS waist was inversely associated with changes in linear PFOA, linear PFOS, PFNA, PFDA, PFUdA, and PFDoA. The associations between PFAS exposure index change with MS and MS waist were robust across sensitivity analyses, including qgcomp. Analyses of continuous metabolic traits showed concordant patterns for waist circumference and HDL-C. Exploratory backward models further suggested that adiposity change may influence measured PFAS change. In this Taiwanese cohort, higher ΔPFAS exposure index was associated with lower odds of MS and abdominal obesity, but the findings are consistent with reciprocal coupling rather than a protective effect of PFAS exposure. Studies with three or more repeated measurements are needed to clarify causal direction and underlying mechanisms.