Association between polycyclic aromatic hydrocarbons (PAHs) and insulin resistance: A comprehensive study utilizing...

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants with potential endocrine-disrupting effects, yet prior epidemiological research on their association with insulin resistance has yielded inconsistent results. Using data from 3294 participants in the National Health and Nutrition Examination Survey (NHANES) cycles from 2005 to 2016, we applied multivariable linear regression, restricted cubic spline models, weighted quantile sum (WQS) regression, and the g-computation model to examine the relationships between individual and mixed PAH exposures and insulin resistance, with subgroup analyses stratified by sex and age. The analyses revealed that 2-hydroxyfluorene (2-FLU) and 1-hydroxyphenanthrene (1-PHE) were significantly positively associated with the triglyceride-glucose index (TyG), metabolic score for insulin resistance (METS-IR), and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) (P < 0.05). Consistently, both weighted quantile sum regression and quantile g-computation demonstrated significant positive associations between PAH mixture exposure and TyG, MEST-IR, triglyceride-glucose-body mass index (TyG-BMI), and TG/HDL-C (P < 0.05), with 2-FLU and 1-PHE identified as dominant contributors. Stratified analyses suggested that women and non-elderly individuals may represent susceptible subpopulations. Network toxicology and molecular docking further indicated that PAHs may disrupt glucose homeostasis by inducing inflammation, promoting oxidative stress, and interfering with insulin signaling pathways. Together, these findings provide both epidemiological and mechanistic evidence for the impact of PAHs on insulin resistance, underscoring the importance of considering PAHs as potential environmental correlates of insulin resistance and related metabolic disorders.