Changes in insulin resistance mediate the associations between phthalate exposure and metabolic syndrome

Information on the relationships between phthalate exposure, insulin resistance, and metabolic syndrome (MetS) in younger adults is limited. It is still unclear whether changes in insulin resistance represent an intermediate biological mechanism linking phthalate exposure and MetS. To investigate the associations between cumulative risk of phthalates (such as daily intake [DI] and hazard index [HI]), insulin resistance, and MetS in younger adults and to examine the mediating role of insulin resistance in the associations between phthalate exposure and MetS. Urinary phthalate metabolite levels, insulin resistance (by using the Homeostatic Model Assessment of estimated Insulin Resistance [HOMA-IR]), and MetS status were determined in 435 military personnel in Taiwan. We estimated the DI of five phthalates: dimethyl phthalate (DMP), diethyl phthalate, dibutyl phthalate, benzyl butyl phthalate (BBzP), and di (2-ethylhexyl) phthalate and the HI based on urinary phthalate metabolite levels. Cross-sectional associations between DI and HI, HOMA-IR, and the indicators of MetS were explored using logistic regression models. Mediation analysis was conducted to assess the role of insulin resistance in the associations between phthalate exposure and MetS. Higher DIDMP was associated with an increased odds of high HOMA-IR and MetS (odds ratio [OR], 1.686; 95% confidence interval [CI], 1.079–2.634 for high HOMA-IR; OR, 2.329; 95% CI, 1.263–4.295 for MetS). The mediation analysis indicated that 43% of the association between higher DIDMP and MetS was mediated by HOMA-IR. Higher DIBBzP and HI were associated with an increased odds of abdominal obesity (OR, 1.816; 95% CI, 1.180–2.797 for the high DIBBzP group; OR, 1.700, 95% CI, 1.105–2.614 for the high HI groups). Exposure to environmental phthalates may be positively associated with insulin resistance and MetS. Insulin resistance may mediate these associations between exposure to certain phthalates and MetS.