Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome
Given the well-documented endocrine-disrupting effects of phthalate plasticizers (PAEs) on human health, their use has been subjected to stringent regulatory restrictions, prompting a global shift toward non-phthalate plasticizers (non-PAEs) as alternatives. While epidemiological evidence has establ...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325007419 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849734336563118080 |
|---|---|
| author | Yingying Mao Shuqin Tang Huan Liu Qing Huang Da Chen Yuanyuan Li Fengjiang Sun Wei Huang |
| author_facet | Yingying Mao Shuqin Tang Huan Liu Qing Huang Da Chen Yuanyuan Li Fengjiang Sun Wei Huang |
| author_sort | Yingying Mao |
| collection | DOAJ |
| description | Given the well-documented endocrine-disrupting effects of phthalate plasticizers (PAEs) on human health, their use has been subjected to stringent regulatory restrictions, prompting a global shift toward non-phthalate plasticizers (non-PAEs) as alternatives. While epidemiological evidence has established significant associations between PAE exposure and gestational diabetes mellitus (GDM), the potential role of non-PAEs in GDM pathogenesis represents a critical knowledge gap in environmental epidemiology. To address this, we conducted a case-control study nested within a well-established prospective birth cohort in Wuhan, China, comprising 286 GDM cases and 286 matched healthy controls. Plasma concentrations of 10 non-PAEs were quantified with high detection frequencies (≥ 70 % for six species). Using multivariable conditional logistic regression and restricted cubic spline regression models adjusted for maternal age, pre-pregnancy body mass index, and other covariates, we identified significant positive associations between gestational exposure to dimethyl azelate (DMAZ), trihexyl trimellitate, di(2-ethylhexyl) maleate, and dibutyl fumarate and elevated GDM risk. In addition, the Bayesian kernel machine regression (BKMR) model further revealed a joint effect of the non-PAE mixture exposure on GDM risk, and DMAZ and diisobutyl adipate/dibutyl adipate (DiBA/DnBA) were identified as key contributors to the joint effect. Our results also demonstrated significant mediation effects of selected lipid molecules (especially phosphatidylcholine and lysophosphatidylcholine) on the associations of DMAZ and DiBA/DnBA with GDM risk. These findings contribute to a deeper understanding of the environmental stressors associated with the development of GDM, as well as the underlying biological mechanisms involving lipid metabolism. |
| format | Article |
| id | doaj-art-10b2a5e4354742ab90b9b8ebcbec9fa1 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-10b2a5e4354742ab90b9b8ebcbec9fa12025-08-20T03:07:50ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0129911840510.1016/j.ecoenv.2025.118405Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidomeYingying Mao0Shuqin Tang1Huan Liu2Qing Huang3Da Chen4Yuanyuan Li5Fengjiang Sun6Wei Huang7College of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, ChinaCollege of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, ChinaCollege of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, ChinaCollege of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, ChinaCollege of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, ChinaKey Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Corresponding authors.College of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, China; Corresponding authors.College of Environment and Climate, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, China; Corresponding authors.Given the well-documented endocrine-disrupting effects of phthalate plasticizers (PAEs) on human health, their use has been subjected to stringent regulatory restrictions, prompting a global shift toward non-phthalate plasticizers (non-PAEs) as alternatives. While epidemiological evidence has established significant associations between PAE exposure and gestational diabetes mellitus (GDM), the potential role of non-PAEs in GDM pathogenesis represents a critical knowledge gap in environmental epidemiology. To address this, we conducted a case-control study nested within a well-established prospective birth cohort in Wuhan, China, comprising 286 GDM cases and 286 matched healthy controls. Plasma concentrations of 10 non-PAEs were quantified with high detection frequencies (≥ 70 % for six species). Using multivariable conditional logistic regression and restricted cubic spline regression models adjusted for maternal age, pre-pregnancy body mass index, and other covariates, we identified significant positive associations between gestational exposure to dimethyl azelate (DMAZ), trihexyl trimellitate, di(2-ethylhexyl) maleate, and dibutyl fumarate and elevated GDM risk. In addition, the Bayesian kernel machine regression (BKMR) model further revealed a joint effect of the non-PAE mixture exposure on GDM risk, and DMAZ and diisobutyl adipate/dibutyl adipate (DiBA/DnBA) were identified as key contributors to the joint effect. Our results also demonstrated significant mediation effects of selected lipid molecules (especially phosphatidylcholine and lysophosphatidylcholine) on the associations of DMAZ and DiBA/DnBA with GDM risk. These findings contribute to a deeper understanding of the environmental stressors associated with the development of GDM, as well as the underlying biological mechanisms involving lipid metabolism.http://www.sciencedirect.com/science/article/pii/S0147651325007419Non-phthalate plasticizersGestational diabetes mellitusMixture effectPlasma lipidomeMediation analysis |
| spellingShingle | Yingying Mao Shuqin Tang Huan Liu Qing Huang Da Chen Yuanyuan Li Fengjiang Sun Wei Huang Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome Ecotoxicology and Environmental Safety Non-phthalate plasticizers Gestational diabetes mellitus Mixture effect Plasma lipidome Mediation analysis |
| title | Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome |
| title_full | Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome |
| title_fullStr | Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome |
| title_full_unstemmed | Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome |
| title_short | Association of non-phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus: The potential mediation effect of plasma lipidome |
| title_sort | association of non phthalate plasticizer exposure during early pregnancy with gestational diabetes mellitus the potential mediation effect of plasma lipidome |
| topic | Non-phthalate plasticizers Gestational diabetes mellitus Mixture effect Plasma lipidome Mediation analysis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325007419 |
| work_keys_str_mv | AT yingyingmao associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT shuqintang associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT huanliu associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT qinghuang associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT dachen associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT yuanyuanli associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT fengjiangsun associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome AT weihuang associationofnonphthalateplasticizerexposureduringearlypregnancywithgestationaldiabetesmellitusthepotentialmediationeffectofplasmalipidome |