Association of exposure to Di-2-ethylhexylphthalate replacements with increased insulin resistance in adolescents from NHANES 2009-2012

Context: Di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP) are environmental chemicals increasingly used to replace di-2-ethylhexylphthalate (DEHP) and commonly found in processed foods. Phthalate exposures, in particular DEHP, have been associated with insulin resistance in adolescents, but there are no data regarding the two substitutes, DINP and DIDP. Objective: This study aimed to examine associations of DINP, DIDP, andDEHPwith insulin resistance outcomes. Design, Setting, and Participants: This was a cross-sectional analysis of 2009-2012 National Health and Nutrition Examination Surveys (NHANES) composed of 356 fasting 12-19-year-olds. Main Outcome Measures: Insulin resistance as a categorical outcome expressed as homeostatic model assessment of insulin resistance (HOMA-IR), using a cut point of 4.39 to define insulin resistance. We also examined continuous HOMA-IR as an outcome in secondary analyses. Results: Controlling for demographic and behavioral factors, diet, age, body mass index, and urinary creatinine, for each log increase in DINP metabolite, a 0.08 (P=.001) increase in HOMA-IR wasidentified.Comparedwith the first tertile ofDINP(23.4% adjusted prevalence), the third tertile was associated with a 34.4% prevalence (95% confidence interval [CI], 27.3-41.6%; P=.033) of insulin resistance. Similarly, compared with the first tertile of DEHP (20.5% adjusted prevalence), the third tertile had 37.7% prevalence (95% CI 29.8-45.6%; P=.003). Conclusions: Urinary DINP concentrations were associated with increased insulin resistance in this cross-sectional study of adolescents. The previously identified association of DEHP with insulin resistance was also confirmed. Further, longitudinal studies are needed to confirm these associations, with the possibility to assess opportunities for intervention.