The role of oxidative stress in cardiometabolic risk related to phthalate exposure in elderly diabetic patients from Shanghai

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.