Potential mechanisms and modifications of dietary antioxidants on the associations between co-exposure to plastic additives and diabetes.

Background: The association of plastic additive mixture exposure with diabetes and the modifying effects of dietary antioxidants are unclear.

Methods: The data from the NHANES 2011-2018 were retrieved, and phthalates and organophosphate esters (OPEs) were selected as exposures. The coexposure effect was analyzed by the environmental risk score (ERS) and quantile g-computation. To mitigate any potential bias caused by using the internal weights, another version of ERS was constructed using the cross-validation approach. The level of dietary antioxidant intake was measured by the composite dietary antioxidant index (CDAI). The biological mechanism underlying the association was studied by the adverse outcome pathway (AOP) framework.

Results: Fifteen chemicals (ten phthalates and five OPEs) were measured in 2824 adult participants. A higher ERS was significantly associated with an increased risk of diabetes (OR per 1-SD increment of ERS: 1.25, 95% CI: 1.13-1.39). This association apparently interacted with the CDAI level (OR_low: 1.83, 95% CI: 1.37-2.55; OR_high: 1.28, 95% CI: 1.15-1.45; P_interaction = 0.038). Moreover, quantile g-computation also revealed higher level of combined exposure was positively associated with diabetes (OR: 1.27, 95% CI: 1.05-2.87), and the addition of dietary antioxidants showed a null association (OR: 1.09, 95% CI: 0.85-2.34). The AOP study identified TCPP and TCEP as key chemicals that cause aberrant glucose metabolism and insulin signaling pathways and result in diabetes.

Conclusions: Coexposure to phthalates and OPEs is positively associated with diabetes, where an antioxidative diet plays a modifying role. Several potential mechanisms have been proposed by AOP framework.