The effect of human exposure to phthalates and consequent contribution to the development of cardiometabolic health problems is unknown. However, oxidative stress has been established as playing an important role in the pathogenesis of cardiometabolic outcomes. In this study, we aimed to explore whether exposure to phthalate metabolites could induce cardiometabolic risk by increasing oxidative stress in a diabetic population from Shanghai. We collected paired blood and urine samples from a total of 300 volunteers, and measured 10 phthalate metabolites in urine and biomarkers of oxidative stress from serum including glucose and lipid levels, and liver and kidney damage. The insulin resistance (IR) risk was assessed by the surrogate indices including homeostasis model assessment-insulin resistance (HOMA-IR) and triglyceride glucose (TyG). We used multivariable linear regression to assess the association between phthalates and these physiological parameters. Mediation and modification analyses were performed to identify the role that oxidative stress played in the underlying mechanisms. The results showed that most of the determined phthalate metabolites were positively associated with HOMA-IR, 8‑hydroxy‑2′‑deoxyguanosine (8-OHDG), and malondialdehyde (MDA). In the mediation analysis, only γ‑glutamiltransferase (GGT) was found to be a significant mediator of the association between phthalates and TyG. In the modification analysis, exposure to phthalates strengthened the association between oxidative stress (MDA and 8-OHDG) and HOMA-IR. Our findings demonstrate that exposure to phthalates might be positively associated with elevated IR and oxidative stress. The direct participation (mediation effect) of GGT might play an important mechanism in promoting IR.

人体暴露于邻苯二甲酸盐的影响及其对心脏代谢健康问题发展的影响尚不清楚。然而，已经确定氧化应激在心脏代谢结果的发病机理中起着重要作用。在这项研究中，我们旨在探讨暴露于邻苯二甲酸酯代谢物是否会通过增加上海糖尿病人群的氧化应激而诱发心脏代谢风险。我们从总共300名志愿者那里收集了成对的血液和尿液样本，并测量了尿液中的10种邻苯二甲酸酯代谢物和血清中的氧化应激生物标志物，包括葡萄糖和脂质水平以及肝肾损害。胰岛素抵抗（IR）风险通过替代指标进行评估，包括体内稳态模型评估-胰岛素抵抗（HOMA-IR）和甘油三酸酯葡萄糖（TyG）。我们使用多元线性回归来评估邻苯二甲酸酯与这些生理参数之间的关联。进行了中介和修饰分析，以确定氧化应激在潜在机制中的作用。结果表明，大多数测定的邻苯二甲酸酯代谢物与HOMA-IR，8-羟基-2'-脱氧鸟苷（8-OHDG）和丙二醛（MDA）正相关。在中介分析中，仅γ-谷氨酰胺转移酶（GGT）被发现是邻苯二甲酸酯与TyG之间缔合的重要介体。在改性分析中，邻苯二甲酸盐的暴露加强了氧化应激（MDA和8-OHDG）与HOMA-IR之间的联系。我们的发现表明，邻苯二甲酸盐的暴露可能与IR和氧化应激升高呈正相关。