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Environ Int. 2019 Feb 21;126:153-161. doi: 10.1016/j.envint.2019.01.082. [Epub ahead of print]

Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia.

Author information

1
Wadsworth Center, New York State Department of Health, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, United States; Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, United States.
2
Bioactive Natural Products Research Group, and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
3
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
4
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Production of Bioproducts for Industrial Applications Research Group and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
5
Wadsworth Center, New York State Department of Health, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, United States; Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, United States; Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Production of Bioproducts for Industrial Applications Research Group and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: Kurunthachalam.kannan@health.ny.gov.

Abstract

Human exposure to phthalates is ubiquitous and has received considerable attention due to their association with adverse health outcomes, including type 2 diabetes mellitus (T2DM). Nevertheless, earlier studies that link phthalate exposure to T2DM yielded ambiguous results. Furthermore, studies that associate phthalate exposure with oxidative stress and then with T2DM are scant. In this diabetic case-control study, urine samples collected from 101 individuals aged 28-68 years from Jeddah, Saudi Arabia, were analyzed to determine 20 phthalate metabolites (PhMs) and seven oxidative stress biomarkers (OSBs). Unconditional logistic regression was used to estimate odds ratios for the association between diabetes and urinary PhMs and OSBs in participants, stratified by age, gender, nationality, smoking status, occupation, and urinary creatinine. Twelve PhMs and five OSBs were found at detection rates above 50%, with geometric mean concentrations of 0.61-100 and 0.35-10.7 ng/mL (1.04-171 and 0.61-18.6 μg/g creatinine), respectively. Almost all exposures were significantly higher in diabetic cases than in controls. The 12 PhMs were positively associated with higher urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F (8-PGF). Individuals in the 3rd and/or 4th quartile(s) for urinary concentrations of PhMs and OSBs showed 3.7- and 7.3-fold increase, respectively, in the odds of having diabetes compared with those in the 1st quartile. The rank order of association of PhMs/OSBs with diabetes followed the order of: mEP ≈ mBP > mEHP > mCPP > mECPP ≈ mEOHP ≈ mEHHP ≈ mIBP ≈ mMP > mCMHP ≈ mBzP and 8-OHdG > 8-PGF ≈ 15-PGF. The relationship between phthalate exposure and risk of developing T2DM was mediated in part by phthalate-induced oxidative stress, especially 8-OHdG. Our study suggests that human exposure to phthalates is associated with increased oxidative stress which mediates the development of T2DM.

KEYWORDS:

Biomonitoring; Diabetes; Oxidative stress; Phthalate metabolites; Urine

PMID:
30798196
DOI:
10.1016/j.envint.2019.01.082
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