Phthalate exposure was reported to be associated with diabetes mellitus (DM) and cardiovascular disease (CVD). Yet, reported associations and the potential sex differences are inconsistent. We conducted a cross-sectional study involving 2330 participants in the Fall of 2012. Urinary metabolites of 10 phthalates were measured. The status of having DM and CVD-related outcomes were self-reported. In the overall study population, the logistic regression analyses showed that the urinary levels of mono-2-ethyl-5-oxohexyphthalate (MEOHP), mono-2-ethyl-5-hydroxyhexylphthalate(MEHHP) and mono-2-ethyl-5-carboxypentylphthalate (MECPP) were positively associated with DM. Higher urinary levels of monomethyl phthalate (MMP) and mono-2-carboxymethyl-hexyl phthalate (MCMHP) were associated with increased odds of hyperlipidemia, while mono-2-ethylhexylphthalate (MEHP) was significantly inverse-associated with hyperlipidemia. We did not observe significant associations for other CVD-related outcomes with phthalate metabolites. When stratifying by sex, MEHHP, MEOHP, MECPP, MCMHP and the micromolar sums of the oxidative metabolites of DEHP (ΣDEHPox) were all significantly related to DM in males, but not in females. No significant sex differences were found in CVD-related outcomes, except the sporadic associations between phthalates and hyperlipidemia. These findings highlight the importance of investigating the sex-specific relationship between phthalates exposure and DM.

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.

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Phthalate exposure has been reported to be associated with obesity (measured by body mass index [BMI]) and central obesity (measured by waist circumference [WC]). Yet, reported associations and the potential gender and age differences are inconsistent. We conducted a cross-sectional study involving 2330 participants in the fall of 2012. Urinary metabolites of ten phthalates were measured. Height, body weight, and waist circumference (WC) were measured using standardized methods. We performed logistic regression analyses to estimate the association between each urine phthalate metabolite (categorized into quartiles) and obesity and central obesity and conducted an additional, stratified analysis to explore the gender and age differences. In the overall study population, higher urinary levels of MMP, MEHHP, and MECPP were associated with increased ratios of central obesity. When stratifying by gender and central obesity, higher urinary levels of MMP, MEHHP, and MEOHP were associated with increased odds of central obesity in females, whereas MBP was significantly associated inversely with central obesity in females. In males, it showed no significant P value for trend (P trend). When stratifying by age in females, higher urinary levels of MEHP, MEOHP, MEHHP, and MECPP were associated with increased odds of central obesity in women aged ≤45 years. In females aged >45 years, it showed no significant P trend. In conclusion, we found that association between phthalates and central obesity was stronger than between phthalates and obesity; association between phthalates and central obesity was stronger in females than in males and was stronger in younger females (aged ≤45 years) than in older females (aged >45 years).

Rosmarinic acid ameliorates ethanol-induced lipid accumulation by reducing fatty acid biosynthesis and tumor necrosis factor-α.