Relationships among phthalate exposure, oxidative stress, and insulin resistance in young military soldiers: A cumulative risk assessment and mediation approach

Tsu-I Hsia; Po-Chin Huang; Hsin-Chang Chen; Yuan-Ting C Lo; Wan-Ting Chang; Yann-Yuh Jou; Han-Bin Huang

doi:10.1016/j.envint.2022.107316

Relationships among phthalate exposure, oxidative stress, and insulin resistance in young military soldiers: A cumulative risk assessment and mediation approach

Environ Int. 2022 Jul:165:107316. doi: 10.1016/j.envint.2022.107316. Epub 2022 May 23.

Authors

Tsu-I Hsia¹, Po-Chin Huang², Hsin-Chang Chen³, Yuan-Ting C Lo⁴, Wan-Ting Chang⁵, Yann-Yuh Jou⁶, Han-Bin Huang⁷

Affiliations

¹ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan ROC.
² National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan ROC; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ROC; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan ROC.
³ Department of Chemistry, Tunghai University, Taichung City, Taiwan ROC.
⁴ School of Public Health, National Defense Medical Center, Taipei, Taiwan ROC.
⁵ National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan ROC.
⁶ Health Promotion Administration, Ministry of Health and Welfare, Taipei, Taiwan ROC.
⁷ School of Public Health, National Defense Medical Center, Taipei, Taiwan ROC. Electronic address: toly2000@gmail.com.

PMID: 35635958
DOI: 10.1016/j.envint.2022.107316

Abstract

Background: Epidemiological studies concerning whether oxidative stress mediates phthalate exposure-insulin resistance (IR) associations in young adults are limited. Therefore, we investigated this potential mediation by using a cumulative risk approach involving daily intake (DI) and a hazard index (HI_RfD).

Methods: The participants were 391 Taiwanese military personnel. This study measured their IR (as homeostatic model assessment of estimated IR [HOMA-IR]), levels of oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine, 8-nitroguanine, 8-iso-prostaglandin F2α, and N-acetyl-S-[tetrahydro-5-hydroxy-2-pentyl-3-furanyl]-L-cysteine [HNE-MA]), the sum of these four biomarkers (ΣOS), and urinary phthalate metabolite concentrations. The HI_RfD was estimated on the basis of urinary levels of phthalate metabolite, and the DI of five phthalates was determined: dimethyl phthalate, benzyl butyl phthalate (BBzP), diethyl phthalate, dibutyl phthalate (DBP), and di (2-ethylhexyl) phthalate (DEHP). Logistic regression models were employed to explore associations among DI, HI_RfD, oxidative stress biomarkers, and HOMA-IR values. The role played by oxidative stress in the phthalate exposure-HOMA-IR association was determined using mediation analysis.

Results: We discovered positive associations between high DI of DBP, BBzP, and DEHP; high HI_RfD; and high ΣOS. High ΣOS and HNE-MA were associated with a higher likelihood of a high HOMA-IR value. Mediation analysis indicated that high ΣOS and HNE-MA were significant mediators of the associations between phthalates and IR.

Conclusion: Oxidative stress may partially mediate the phthalate-IR relationship in young adults.

Keywords: Cumulative risk; Insulin resistance; Oxidative stress; Phthalate; Young adult.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / urine
Dibutyl Phthalate / urine
Diethylhexyl Phthalate* / metabolism
Environmental Exposure / analysis
Environmental Pollutants* / analysis
Humans
Insulin Resistance*
Military Personnel*
Oxidative Stress
Phthalic Acids* / urine
Risk Assessment
Young Adult

Substances

Biomarkers
Environmental Pollutants
Phthalic Acids
Dibutyl Phthalate
phthalic acid
Diethylhexyl Phthalate