Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones

Jiayu Shi; Dandan Wei; Cuicui Ma; Jintian Geng; Mengzhen Zhao; Jian Hou; Wenqian Huo; Tao Jing; Chongjian Wang; Zhenxing Mao

doi:10.1016/j.envpol.2023.122867

Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones

Environ Pollut. 2024 Jan 15:341:122867. doi: 10.1016/j.envpol.2023.122867. Epub 2023 Nov 7.

Authors

Jiayu Shi¹, Dandan Wei¹, Cuicui Ma¹, Jintian Geng¹, Mengzhen Zhao¹, Jian Hou¹, Wenqian Huo², Tao Jing³, Chongjian Wang¹, Zhenxing Mao⁴

Affiliations

¹ Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China.
² Department of Occupational and Environmental Health Sciences, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China.
³ School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
⁴ Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China. Electronic address: mzx@zzu.edu.cn.

PMID: 37944891
DOI: 10.1016/j.envpol.2023.122867

Abstract

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes.

Keywords: Combined exposure; Methylation; Organochlorine pesticides; Testosterone; Type 2 diabetes mellitus.

MeSH terms

Bayes Theorem
Case-Control Studies
Diabetes Mellitus, Type 2* / chemically induced
Dichlorodiphenyl Dichloroethylene / analysis
Female
Gonadal Steroid Hormones
Humans
Hydrocarbons, Chlorinated* / analysis
Male
Pesticides* / analysis
Testosterone

Substances

Dichlorodiphenyl Dichloroethylene
Hydrocarbons, Chlorinated
Pesticides
Testosterone
Gonadal Steroid Hormones