Background

Epidemiological studies concerning whether oxidative stress mediates phthalate exposure–insulin resistance (IR) associations in young adults are limited. Therefore, we investigated this potential mediation by using a cumulative risk approach involving daily intake (DI) and a hazard index (HI_RfD).

Methods

The participants were 391 Taiwanese military personnel. This study measured their IR (as homeostatic model assessment of estimated IR [HOMA-IR]), levels of oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine, 8-nitroguanine, 8-iso-prostaglandin F2α, and N-acetyl-S-[tetrahydro-5-hydroxy-2-pentyl-3-furanyl]-L-cysteine [HNE-MA]), the sum of these four biomarkers (ΣOS), and urinary phthalate metabolite concentrations. The HI_RfD was estimated on the basis of urinary levels of phthalate metabolite, and the DI of five phthalates was determined: dimethyl phthalate, benzyl butyl phthalate (BBzP), diethyl phthalate, dibutyl phthalate (DBP), and di (2-ethylhexyl) phthalate (DEHP). Logistic regression models were employed to explore associations among DI, HI_RfD, oxidative stress biomarkers, and HOMA-IR values. The role played by oxidative stress in the phthalate exposure–HOMA-IR association was determined using mediation analysis.

Results

We discovered positive associations between high DI of DBP, BBzP, and DEHP; high HI_RfD; and high ΣOS. High ΣOS and HNE-MA were associated with a higher likelihood of a high HOMA-IR value. Mediation analysis indicated that high ΣOS and HNE-MA were significant mediators of the associations between phthalates and IR.

Conclusion

Oxidative stress may partially mediate the phthalate–IR relationship in young adults.