Relationship between per-fluoroalkyl and polyfluoroalkyl substance exposure and insulin resistance in nondiabetic adults: Evidence from NHANES 2003–2018

• Published in: Ecotoxicology and environmental safety 2024-11, Vol.287, p.117260, Article 117260
• Main Authors: Jia, Peng, Yu, Xinwen, Jin, Yuxin, Wang, Xin, Yang, Aili, Zhang, Li, Jing, Xiaorui, Kang, Weiwei, Zhao, Guohong, Gao, Bin
• Format: Article
• Language: English
• Subjects: Insulin resistance; NHANES; Per-fluoroalkyl substances; Polyfluoroalkyl substances; Triglyceride-glucose index
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.117260

Studies have linked per- and polyfluoroalkyl substances (PFAS) to chronic metabolic diseases. However, the relationship between PFAS exposure and insulin resistance (IR), a key pathophysiological basis of these metabolic diseases, in nondiabetic individuals have yet to be determined. This study analyzed data from 3909 participants (aged ≥20) from the NHANES 2003–2018 to investigate the associations between serum levels of seven PFAS and and IR indicators, including including HOMA-IR, HOMA-β, fasting insulin, QUICKI, and TyG index. Linear and logistic regression models were used, along with a restricted cubic spline to assess dose-response. Weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models were used to assess the association between mixed PFAS exposure and IR. Linear regression revealed that elevated exposure to PFOS [β (95 % CI): 0.04 (0.02, 0.06)], PFOA [0.04 (0.01, 0.06)], and Me_PFOSA_AcOH [0.04 (0.02, 0.06)] was associated with a higher TyG index in adults. Notably, Me_PFOSA_AcOH was negatively associated with IR when assessed by HOMA-IR >2.6 [OR (95 % CI): 0.88 (0.79, 0.98)], although this was not supported by linear regression findings. When IR was defined by a TyG index >8.6, exposure to the highest quartiles of PFOS, PFOA, and Me_PFOSA_AcOH was associated with an increased risk of IR by 63 %, 42 %, and 85 %, respectively [1.63 (1.21, 2.20); 1.42 (1.06, 1.92); 1.85 (1.37, 2.50)]. PFOS, PFOA, and Me_PFOSA_AcOH demonstrated a nonlinear dose-response relationship with IR risk. The WQS and qgcomp models revealed significant positive correlations with the TyG index. Mixed PFAS exposure in US nondiabetic adults was positively associated with IR, as indicated by the TyG index, particularly for PFOS, PFOA, and Me_PFOSA_AcOH. Further research is needed to establish causality, and reinforcing environmental risk mitigation strategies to reduce PFAS exposure is recommended. [Display omitted] •Mixed PFAS exposure are linked to increased TyG index in U.S. nondiabetic adults.•PFOS, PFOA, and Me_PFOSA_AcOH are associated with increased IR by the TyG index.•PFAS exposure shows a significant nonlinear relationship with the TyG index.