Exposure to phthalates in patients with diabetes and its association with oxidative stress, adiponectin, and inflammatory cytokines

Epidemiologic studies have revealed higher concentrations of the metabolites of phthalic acid esters (mPAEs) in patients with type 2 diabetes. On the other hand, oxidative stress, adiponectin, and inflammatory cytokines play important roles in the pathogenesis of diabetes and its complications. However, little information is known about the association between exposure to PAEs and these physiological parameters. Hence, paired urine and blood samples were collected from a total of 329 volunteers, and 11 main mPAEs and malondialdehyde (MDA), as a biomarker of oxidative stress, were measured in the urine samples. Serum adiponectin and tumor necrosis factor-alpha (TNF-alpha), a biomarker of inflammation, were also measured. Multivariable linear regression was used to assess the association between urinary mPAEs and these physiological parameters in the total subjects and subjects stratified by age, sex, and body mass index (BMI) to elucidate their possible interactions. All 11 mPAEs were detected in the urine with detection rates of 42.9%-100% and geometric means of 0.30-54.52 mu g/mL (0.44-79.93 pg/g creatinine). The mPAEs were all positively associated with MDA levels. There were significant positive associations between monomethyl phthalate (mMP) and TNF-alpha, and inverse associations between mMP and adiponectin levels. In the stratified analysis, there were age-, sex-, and BMI-specific differences for these associations. The positive associations between mPAEs and MDA were insignificant in some subgroups, especially in the larger age group. However, in the larger BMI group, summed metabolites of di-(2-ethylhexyl) phthalate (Sigma DEHP) and mono(2-ethylhexyl) phthalate were positively associated with TNF-alpha, and the concentrations of Sigma DEHP were negatively associated with adiponectin. Our findings suggested that PAE exposure is associated with oxidative stress, adiponectin, and inflammatory cytokines in diabetic patients; further studies on toxicology and a comparison with general population are needed.