Metabolite profiling of organophosphate ester exposure and type 2 diabetes mellitus risk: A metabolomics study in an epidemiological setting.

Organophosphate esters (OPEs), a class of widespread new environmental contaminants, have garnered increasing attention due to their potential adverse health effects. However, the evidence regarding the association between OPEs and T2DM remains lacking. We conducted a case-control study, serum samples from 144 T2DM-diagnosed individuals and 144 healthy controls were analyzed for the presence of 11 OPEs. Significantly higher levels of each OPE homologue in the T2DM group were observed, with chlorinated OPEs being predominantly present in both groups. Associations between OPEs and T2DM risk were evaluated by conditional Firth logistic regression and BKMR models, suggesting that tris (2-butoxyethyl) phosphate (TBEP), tri[(2 R)-1-chloro-2-propyl] phosphate (TCPP), and tris (1,3-dichloro-2-propyl) phosphate (TDCPP) were significantly associated with higher odds of T2DM. A comprehensive metabolomics analysis combining targeted and non-targeted approaches to obtain broad metabolic profiles of the study participants. This analysis identified 53 metabolites and 8 metabolic pathways significantly correlated with key OPEs and linked to T2DM risk. Alterations in amino acid and lipid metabolism were observed in association with OPE exposure, showing patterns consistent with insulin secretion and glucose dysregulation. LysoPEs, 1,5-AG, and polyunsaturated fatty acids exhibited patterns consistent with potential mediation between TBEP and T2DM. Overall, our findings suggest associations between OPE exposure and T2DM risk, with metabolite profiles suggesting potential biological pathways warranting further investigation.