Association of Serum Organophosphorus Pesticide Levels with T2D Risk and Blood Glucose Changes: A Nested Case–Control Study

Organophosphorus pesticides (OPs) are widely used in agriculture, but prospective studies on their chronic exposure and risk of type 2 diabetes (T2D) and glucose metabolism disorders are scarce. Most previous studies focused on agricultural workers and relied on questionnaires or urinary metabolites for exposure assessment. We conducted a nested case–control study with 1006 pairs of participants based on the Dongfeng–Tongji cohort to investigate the association between serum OP levels, T2D risk, and fasting blood glucose (FBG) changes over a 5-year follow-up. Serum OP concentrations were measured by gas chromatography–triple quadrupole mass spectrometry. Among the 29 types of OPs detected, Chlorpyrifos and Fenitrothion had detection rates of 99.9% and 87.9%, respectively. Etrimfos and Parathion were detected in 75.8% and 64.5% of participants. Four types of OPs—Ethoprophos, Phorate, Diazinon, and Malathion, categorized into ≤LOD and >LOD groups—had detection rates ranging from 20% to 60%. OP exposure was not associated with T2D risk in the overall population. Among participants with baseline FBG ≥ 6.1 mmol/L, OP exposure showed a positive association with incident T2D and with increases in FBG during a 5-year follow-up. In contrast, OP exposure was associated with decreased FBG in the overall population. Moreover, significant interactions were observed between OP exposure and baseline FBG levels (P_interaction < 0.05), suggesting that baseline glucose levels may modify the metabolic effects of chronic OP exposure. These findings highlight the importance of considering basal glucose status when evaluating the long-term metabolic effects of OP exposure.