Phthalate exposure and risk of diabetes mellitus: Implications from a systematic review and meta-analysis

Epidemiologic studies indicated that phthalate exposure might be associated with diabetes mellitus (DM). However, discrepancies existed. The link between phthalate exposure and risk of DM remained unclarified.We conducted a meta-analysis to explore the association between phthalate exposure and risk of DM. Effects of phthalate exposure on insulin resistance were also evaluated by systematic review.Seven studies involving 12,139 participants were included in this meta-analysis. Our results showed that urinary concentrations of phthalates were positively associated with risk of DM. The pooled ORs were 3.11 (95% CI: 1.16-8.37) for monomethyl phthalate (MMP), 1.27 (95% CI: 1.03-1.56) for mono-n-butyl phthalate (MnBP), 2.59 (95% CI: 1.10-6.10) for mono-isobutyl phthalate (MiBP), 1.99 (95% CI: 1.52-2.61) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), 1.90 (95% CI: 1.40-2.57) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 1.55 (95% CI: 1.10-2.20) for mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and 2.39 (95% CI: 1.18-4.85) for mono-(3-carboxypropyl) phthalate (MCPP), respectively. Molar summation of di-2-ethylhexyl phthalate metabolites (∑DEHP) was also found to be correlated with risk of DM (OR 2.15, 95% CI: 1.48-3.13). No significant association with risk of DM was found regarding monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and mono(2-ethylhexyl) phthalate (MEHP). In literature review, most studies showed positive correlations of phthalates, especially ∑DEHP, with homeostasis model assessment of insulin resistance and fasting glucose.Exposure to phthalates, especially MMP, MnBP, MiBP, MCPP and DEHP metabolites, might be a risk factor of DM. Our results should be interpreted with caution due to heterogeneous design of enrolled studies.