Comprehensive metabolomics reveals glycolipid metabolic disturbance and potential biomarkers in Chinese diesel exhaust-exposed workers: A cohort study.

Diesel exhaust (DE) is a significant contributor to the traffic-related air pollution (TRAP) and has been linked to multiple adverse health outcomes. However, research on glycolipid metabolic disturbance associated with human exposure to DE remains scarce. Based on the cohort of diesel engine testers (DETs), this study revealed that DE exposure could disrupt liver function and interfere with the glucose and lipid metabolism in humans. By combining targeted analyses of amino acids and fatty acids with untargeted lipidomics approaches, we comprehensively elucidated the altered plasma metabolic profiles induced by DE exposure. A total of 8 amino acids, 3 fatty acids, and 36 lipids were identified as differential metabolites. These perturbed metabolites further indicate the impaired glycolipid metabolism, and furnish evidence of the adverse health risks resulting from DE exposure, primarily encompassing insulin resistance, cardiovascular diseases (CVDs), liver diseases, and neurotoxicity. A machine learning-based regression algorithm identified metabolites that are likely to mediate changes in the clinical indicators related to glycolipid metabolism. Mediation analysis and validation cohort showed that alanine (Ala), AcCa(21:1), and PC(38:1) potentially serve as early predictive biomarkers for DE-induced alterations in glucose levels. This study offers the first metabolic evidence establishing a link between DE exposure and glycolipid metabolic disturbance, highlighting the potential health risks posed by TRAP.