邻苯二甲酸酯暴露、氧化应激与青年军人胰岛素抵抗的关系：累积风险评估与中介作用分析。
Relationships among phthalate exposure, oxidative stress, and insulin resistance in young military soldiers: A cumulative risk assessment and mediation approach.
机构信息
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan ROC.
National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan ROC; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ROC; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan ROC.
出版信息
Environ Int. 2022 Jul;165:107316. doi: 10.1016/j.envint.2022.107316. Epub 2022 May 23.
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).
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 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, 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; 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.
背景
关于氧化应激是否介导了年轻人中邻苯二甲酸酯暴露与胰岛素抵抗（IR）之间的关系，流行病学研究有限。因此，我们采用了累积风险方法，通过每日摄入量（DI）和危害指数（HI）来研究这种潜在的中介作用。
方法
研究对象为 391 名台湾军人。本研究测量了他们的 IR（作为稳态模型评估的估计 IR [HOMA-IR]）、氧化应激生物标志物（8-羟基-2-脱氧鸟苷、8-硝基鸟嘌呤、8-异前列腺素 F2α 和 N-乙酰-S-[四氢-5-羟基-2-戊基-3-呋喃基]-L-半胱氨酸[HNE-MA]）、这四种生物标志物的总和（ΣOS）以及尿邻苯二甲酸代谢物浓度。HI 是根据尿中邻苯二甲酸代谢物水平估算的，而 5 种邻苯二甲酸的 DI 则由以下物质决定：邻苯二甲酸二甲酯、邻苯二甲酸丁基苄酯（BBzP）、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯（DBP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）。采用 logistic 回归模型探讨 DI、HI、氧化应激生物标志物和 HOMA-IR 值之间的关联。采用中介分析确定氧化应激在邻苯二甲酸酯暴露与 HOMA-IR 关联中的作用。
结果
我们发现 DBP、BBzP 和 DEHP 的 DI 高、HI 高、ΣOS 高均与 HOMA-IR 值升高呈正相关。高 ΣOS 和 HNE-MA 与 HOMA-IR 值升高的可能性更高有关。中介分析表明，高 ΣOS 和 HNE-MA 是邻苯二甲酸酯与 IR 之间关联的重要中介因素。
结论
氧化应激可能部分介导了年轻人中邻苯二甲酸酯与 IR 之间的关系。
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