TY - JOUR
T1 - Serum beta-carotene modifies the association between phthalate mixtures and insulin resistance
T2 - The National Health and Nutrition Examination Survey 2003–2006
AU - Li, Ming Chieh
AU - Mínguez-Alarcón, Lidia
AU - Bellavia, Andrea
AU - Williams, Paige L.
AU - James-Todd, Tamarra
AU - Hauser, Russ
AU - Chavarro, Jorge E.
AU - Chiu, Yu Han
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11
Y1 - 2019/11
N2 - Animal models suggest a protective role of antioxidants against the adverse effect of di-2-ethylhexyl phthalate (DEHP) on insulin resistance. However, no epidemiologic study has examined the effects observed in the animal model. We conduct a study to examine associations of urinary concentrations of phthalate metabolites (individually and as a mixture) with insulin resistance, along with potential effect modification by serum antioxidant concentrations. This cross-sectional study included 1605 participants (51% males) aged 12–85 from the National Health and Nutrition Examination Surveys (2003–2006). Urinary concentrations of 9 phthalate metabolites were measured from spot urine samples. Antioxidant (vitamin A, C, E, and carotenoids) concentrations were measured from a fasting serum sample. We used Bayesian Kernel Machine Regression (BKMR) to evaluate associations between phthalate metabolite mixtures and insulin resistance, and examined whether serum antioxidant levels modified these associations, while accounting for the correlations of multiple concurrent exposures. A change in urinary ΣDEHP concentrations from the 25th to the 75th percentile was associated with a higher log HOMA-IR of 0.07 (95% CI = 0.01, 0.14) (4.85% increase in HOMA-IR). In contrast, the same change in urinary monoethyl phthalate (MEP) was associated with a lower HOMA-IR of −0.07 (95% CI = −0.14, −0.02) (6.68% decrease in HOMA-IR). The positive association between ΣDEHP and HOMA-IR became weaker at higher concentrations of serum β-carotene. The relationship between MEP and HOMA-IR, however, was not modified by the serum antioxidants examined. The remaining phthalate metabolites were unrelated to HOMA-IR. In this cross-sectional study, the positive association between DEHP exposure and insulin resistance weakened among participants with higher concentrations of serum β-carotene. As this is the first human report on the protective role of serum β-carotene on DEHP induced insulin resistance, future studies are needed.
AB - Animal models suggest a protective role of antioxidants against the adverse effect of di-2-ethylhexyl phthalate (DEHP) on insulin resistance. However, no epidemiologic study has examined the effects observed in the animal model. We conduct a study to examine associations of urinary concentrations of phthalate metabolites (individually and as a mixture) with insulin resistance, along with potential effect modification by serum antioxidant concentrations. This cross-sectional study included 1605 participants (51% males) aged 12–85 from the National Health and Nutrition Examination Surveys (2003–2006). Urinary concentrations of 9 phthalate metabolites were measured from spot urine samples. Antioxidant (vitamin A, C, E, and carotenoids) concentrations were measured from a fasting serum sample. We used Bayesian Kernel Machine Regression (BKMR) to evaluate associations between phthalate metabolite mixtures and insulin resistance, and examined whether serum antioxidant levels modified these associations, while accounting for the correlations of multiple concurrent exposures. A change in urinary ΣDEHP concentrations from the 25th to the 75th percentile was associated with a higher log HOMA-IR of 0.07 (95% CI = 0.01, 0.14) (4.85% increase in HOMA-IR). In contrast, the same change in urinary monoethyl phthalate (MEP) was associated with a lower HOMA-IR of −0.07 (95% CI = −0.14, −0.02) (6.68% decrease in HOMA-IR). The positive association between ΣDEHP and HOMA-IR became weaker at higher concentrations of serum β-carotene. The relationship between MEP and HOMA-IR, however, was not modified by the serum antioxidants examined. The remaining phthalate metabolites were unrelated to HOMA-IR. In this cross-sectional study, the positive association between DEHP exposure and insulin resistance weakened among participants with higher concentrations of serum β-carotene. As this is the first human report on the protective role of serum β-carotene on DEHP induced insulin resistance, future studies are needed.
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U2 - 10.1016/j.envres.2019.108729
DO - 10.1016/j.envres.2019.108729
M3 - Article
C2 - 31521963
AN - SCOPUS:85072032306
SN - 0013-9351
VL - 178
JO - Environmental Research
JF - Environmental Research
M1 - 108729
ER -
