Association between phthalate exposure and glycosylated hemoglobin, fasting glucose, and type 2 diabetes mellitus: A case-control study in China

Epidemiological studies have shown that exposure to phthalates (PAEs) is associated with type 2 diabetes mellitus (T2DM) and related markers, but limited evidence has been found in Chinese people. Given that China has the highest number of people with DM and Chinese people show relatively higher exposure levels of PAEs, a case-control study was conducted in China to explore the associations of PAE exposure with T2DM and two glycemic indicators, including fasting glucose and glycosylated hemoglobin (HbA1c). Two hundred fifty people with T2DM and 250 controls were recruited in this study. Multivariable logistic regression analyses showed significant positive associations between urinary concentrations of most studied PAE metabolites (mPAEs) and T2DM, with odd ratios comparing extreme mPAEs quartiles ranging from 2.09 to 40.53, whereas two secondary metabolites, mono (2-ethyl-5-carboxypentyl) phthalate and mono [(2-carboxymethyl) hexyl] phthalate showed significant inverse relationships with T2DM. In addition, multivariable linear regression analyses showed that urinary concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate were positively associated with HbA1c levels in controls (β = 0.013; 95% CI: 0.003, 0.023). A significant positive association was also observed for urinary mono (2-ethylhexyl) phthalate and fasting glucose (β = 0.009; 95% CI: 0.002, 0.016). In the stratified analyses, the significant associations of mPAEs with T2DM were more likely to be observed in the younger people, compared to the older people. The significant positive associations between urinary mPAEs and HbA1c levels were more likely to be found in the lower body mass index (BMI) subgroup. Additionally, urinary specific mPAEs were found to be significantly positively related to fasting glucose in males and the older people. The findings suggest that exposure to PAEs is associated with T2DM, fasting glucose, and HbA1c levels in Chinese people and the associations of exposure to PAEs with T2DM, fasting glucose, and HbA1c may differ between sexes, BMIs, or ages.