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Associations of bisphenol exposure with the risk of gestational diabetes mellitus: a nested case–control study in Guangxi, China

  • Challenges in Managing and Risk Assessment of Emerging Environmental Pollutants
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Abstract

A growing number of epidemiologic studies have estimated the associations between endocrine-disrupting chemicals and gestational diabetes mellitus (GDM). However, reports on the association between bisphenol A (BPA) substitutes and GDM are limited. This investigation aimed to explore the associations of maternal serum BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) with the risk of GDM. A nested case–control study was performed among 500 pregnant women. In conditional logistic regression models, the OR for BPS was significantly increased in the medium exposure groups (OR = 1.77; 95% CI: 1.01, 3.13) compared with the reference group, while BPA (OR: 0.38, 95%CI: 0.29, 0.50) and TBBPA (OR: 0.67, 95%CI: 0.54, 0.85) were negatively associated with the risk of GDM. In the Bayesian kernel machine regression (BKMR) analysis, the joint effect of bisphenols was positively associated with the risk of GDM. BPS showed positively relationship, while BPA and TBBPA showed negatively relationship, respectively. The quantile g-computation revealed a statistically significant and negative joint effect of the five bisphenols on the risk of GDM (OR: 0.57; 95% CI: 0.46, 0.72) with BPA (70.2%), TBBPA (21.3%), and BPB (8.5%) had positive contribution to the overall effect. These findings suggested that BPS had a positive effect on the risk of GDM, while BPA and TBBPA had negative effect on the risk of GDM. Moreover, exposure to the mixture of the five bisphenols was negatively associated with the risk of GDM.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Alonso-Magdalena P, Laribi O, Ropero AB, Fuentes E, Ripoll C, Soria B, Nadal A (2005) Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. Environ Health Perspect 113:969–977

    CAS  Google Scholar 

  • American-Diabetes-Association (2013) Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Suppl 1):S67-74

    Google Scholar 

  • Batista TM, Alonso-Magdalena P, Vieira E, Amaral ME, Cederroth CR, Nef S, Quesada I, Carneiro EM, Nadal A (2012) Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice. PLoS One 7:e33814

    CAS  Google Scholar 

  • Bellavia A, Cantonwine DE, Meeker JD, Hauser R, Seely EW, McElrath TF, James-Todd T (2018) Pregnancy urinary bisphenol-A concentrations and glucose levels across BMI categories. Environ Int 113:35–41

    CAS  Google Scholar 

  • Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, Godleski JJ, Coull BA (2015) Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics 16:493–508

    Google Scholar 

  • Bobb JF, Claus Henn B, Valeri L, Coull BA (2018) Statistical software for analyzing the health effects of multiple concurrent exposures via Bayesian kernel machine regression. Environ Health 17:67

    Google Scholar 

  • Burlina S, Dalfrà MG, Lapolla A (2019) Short- and long-term consequences for offspring exposed to maternal diabetes: a review. J Matern Fetal Neonatal Med 32:687–694

    CAS  Google Scholar 

  • Carrico C, Gennings C, Wheeler DC, Factor-Litvak P (2015) Characterization of weighted quantile sum regression for highly correlated data in a risk analysis setting. J Agric Biol Environ Stat 20:100–120

    Google Scholar 

  • Chiu YH, Mínguez-Alarcón L, Ford JB, Keller M, Seely EW, Messerlian C, Petrozza J, Williams PL, Ye X, Calafat AM, Hauser R, James-Todd T (2017) Trimester-Specific urinary bisphenol A concentrations and blood glucose levels among pregnant women from a fertility clinic. J Clin Endocrinol Metab 102:1350–1357

    Google Scholar 

  • Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, Dietz PM (2007) Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care 30:2070–2076

    Google Scholar 

  • Cobellis L, Colacurci N, Trabucco E, Carpentiero C, Grumetto L (2009) Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women. Biomed Chromatogr 23:1186–1190

    CAS  Google Scholar 

  • Covaci A, Voorspoels S, Abdallah MA, Geens T, Harrad S, Law RJ (2009) Analytical and environmental aspects of the flame retardant tetrabromobisphenol-A and its derivatives. J Chromatogr A 1216:346–363

    CAS  Google Scholar 

  • Ding S, Fan Y, Zhao N, Yang H, Ye X, He D, Jin X, Liu J, Tian C, Li H, Xu S, Ying C (2014) High-fat diet aggravates glucose homeostasis disorder caused by chronic exposure to bisphenol A. J Endocrinol 221:167–179

    CAS  Google Scholar 

  • Ehrlich S, Lambers D, Baccarelli A, Khoury J, Macaluso M, Ho SM (2016) Endocrine disruptors: a potential risk factor for gestational diabetes mellitus. Am J Perinatol 33:1313–1318

    Google Scholar 

  • Farahvar S, Walfisch A, Sheiner E (2019) Gestational diabetes risk factors and long-term consequences for both mother and offspring: a literature review. Expert Rev Endocrinol Metab 14:63–74

    CAS  Google Scholar 

  • Filardi T, Panimolle F, Lenzi A, Morano S (2020) Bisphenol A and phthalates in diet: an emerging link with pregnancy complications. Nutrients 12:525

  • Fisher BG, Frederiksen H, Andersson AM, Juul A, Thankamony A, Ong KK, Dunger DB, Hughes IA, Acerini CL (2018) Serum phthalate and triclosan levels have opposing associations with risk factors for gestational diabetes mellitus. Front Endocrinol (lausanne) 9:99

    Google Scholar 

  • Hou Y, Li S, Xia L, Yang Q, Zhang L, Zhang X, Liu H, Huo R, Cao G, Huang C, Tian X, Sun L, Cao D, Zhang M, Zhang Q, Tang N (2021) Associations of urinary phenolic environmental estrogens exposure with blood glucose levels and gestational diabetes mellitus in Chinese pregnant women. Sci Total Environ 754:142085

    CAS  Google Scholar 

  • Jiang S, Miao J, Wang X, Liu P, Pan L (2019) Inhibition of growth in juvenile manila clam Ruditapes philippinarum: potential adverse outcome pathway of TBBPA. Chemosphere 224:588–596

    CAS  Google Scholar 

  • Jin H, Zhu J, Chen Z, Hong Y, Cai Z (2018) Occurrence and partitioning of bisphenol analogues in adults’ blood from China. Environ Sci Technol 52:812–820

    CAS  Google Scholar 

  • Keil AP, Buckley JP, O’Brien KM, Ferguson KK, Zhao S, White AJ (2020) A quantile-based g-computation approach to addressing the effects of exposure mixtures. Environ Health Perspect 128:47004

    Google Scholar 

  • Kitamura S, Suzuki T, Sanoh S, Kohta R, Jinno N, Sugihara K, Yoshihara S, Fujimoto N, Watanabe H, Ohta S (2005) Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds. Toxicol Sci 84:249–259

    CAS  Google Scholar 

  • Kolatorova Sosvorova L, Chlupacova T, Vitku J, Vlk M, Heracek J, Starka L, Saman D, Simkova M, Hampl R (2017) Determination of selected bisphenols, parabens and estrogens in human plasma using LC-MS/MS. Talanta 174:21–28

    CAS  Google Scholar 

  • Konieczna A, Rutkowska A, Rachoń D (2015) Health risk of exposure to Bisphenol A (BPA). Rocz Panstw Zakl Hig 66:5–11

    Google Scholar 

  • Lebeaux RM, Doherty BT, Gallagher LG, Zoeller RT, Hoofnagle AN, Calafat AM, Karagas MR, Yolton K, Chen A, Lanphear BP, Braun JM, Romano ME (2020) Maternal serum perfluoroalkyl substance mixtures and thyroid hormone concentrations in maternal and cord sera: The HOME Study. Environ Res 185:109395

    CAS  Google Scholar 

  • Li A, Zhuang T, Shi W, Liang Y, Liao C, Song M, Jiang G (2020) Serum concentration of bisphenol analogues in pregnant women in China. Sci Total Environ 707:136100

    CAS  Google Scholar 

  • Liang J, Liu S, Liu T, Yang C, Wu Y, Jennifer Tan HJ, Wei B, Ma X, Feng B, Jiang Q, Huang D, Qiu X (2020) Association of prenatal exposure to bisphenols and birth size in Zhuang ethnic newborns. Chemosphere 252:126422

    CAS  Google Scholar 

  • Liu J, Wattar N, Field CJ, Dinu I, Dewey D, Martin JW (2018a) Exposure and dietary sources of bisphenol A (BPA) and BPA-alternatives among mothers in the APrON cohort study. Environ Int 119:319–326

    CAS  Google Scholar 

  • Liu S, Le May C, Wong WP, Ward RD, Clegg DJ, Marcelli M, Korach KS, Mauvais-Jarvis F (2009) Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes 58:2292–2302

    CAS  Google Scholar 

  • Liu X, Zhang L, Li J, Meng G, Chi M, Li T, Zhao Y, Wu Y (2018b) A nested case-control study of the association between exposure to polybrominated diphenyl ethers and the risk of gestational diabetes mellitus. Environ Int 119:232–238

    CAS  Google Scholar 

  • Lu Y, Wang E, Chen Y, Zhou B, Zhao J, Xiang L, Qian Y, Jiang J, Zhao L, Xiong X, Lu Z, Wu D, Liu B, Yan J, Zhang R, Zhang H, Hu C, Li X (2020) Obesity-induced excess of 17-hydroxyprogesterone promotes hyperglycemia through activation of glucocorticoid receptor. J Clin Invest 130:3791–3804

    CAS  Google Scholar 

  • Martínez-Ibarra A, Martínez-Razo LD, Vázquez-Martínez ER, Martínez-Cruz N, Flores-Ramírez R, García-Gómez E, López-López M, Ortega-González C, Camacho-Arroyo I, Cerbón M (2019) Unhealthy levels of phthalates and bisphenol A in Mexican pregnant women with gestational diabetes and its association to altered expression of miRNAs involved with metabolic disease. Int J Mol Sci 20:3343

  • Meng Z, Wang D, Yan S, Li R, Yan J, Teng M, Zhou Z, Zhu W (2018) Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring. Chemosphere 212:297–306

    CAS  Google Scholar 

  • Michałowicz J (2014) Bisphenol A–sources, toxicity and biotransformation. Environ Toxicol Pharmacol 37:738–758

    Google Scholar 

  • Minatoya M, Itoh S, Yamazaki K, Araki A, Miyashita C, Tamura N, Yamamoto J, Onoda Y, Ogasawara K, Matsumura T, Kishi R (2018) Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children’s Health. Environ Health Prev Med 23:43

    Google Scholar 

  • Nadal A, Ropero AB, Fuentes E, Soria B, Ripoll C (2004) Estrogen and xenoestrogen actions on endocrine pancreas: from ion channel modulation to activation of nuclear function. Steroids 69:531–536

    CAS  Google Scholar 

  • Nadal A, Alonso-Magdalena P, Soriano S, Quesada I, Ropero AB (2009) The pancreatic beta-cell as a target of estrogens and xenoestrogens: implications for blood glucose homeostasis and diabetes. Mol Cell Endocrinol 304:63–68

    CAS  Google Scholar 

  • Nelson DB, McIntire DD, McDonald J, Gard J, Turrichi P, Leveno KJ (2017) 17-alpha Hydroxyprogesterone caproate did not reduce the rate of recurrent preterm birth in a prospective cohort study. Am J Obstet Gynecol 216:600.e1-600.e9

    CAS  Google Scholar 

  • Owczarek K, Kubica P, Kudłak B, Rutkowska A, Konieczna A, Rachoń D, Namieśnik J, Wasik A (2018) Determination of trace levels of eleven bisphenol A analogues in human blood serum by high performance liquid chromatography-tandem mass spectrometry. Sci Total Environ 628–629:1362–1368

    Google Scholar 

  • Rancière F, Botton J, Slama R, Lacroix MZ, Debrauwer L, Charles MA, Roussel R, Balkau B, Magliano DJ (2019) Exposure to bisphenol A and bisphenol S and incident type 2 diabetes: a case-cohort study in the french cohort D. E. S. I. R. Environ Health Perspect 127:107013

    Google Scholar 

  • Rebarber A, Istwan NB, Russo-Stieglitz K, Cleary-Goldman J, Rhea DJ, Stanziano GJ, Saltzman DH (2007) Increased incidence of gestational diabetes in women receiving prophylactic 17alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery. Diabetes Care 30:2277–2280

    CAS  Google Scholar 

  • Robledo C, Peck JD, Stoner JA, Carabin H, Cowan L, Koch HM, Goodman JR (2013) Is bisphenol-A exposure during pregnancy associated with blood glucose levels or diagnosis of gestational diabetes? J Toxicol Environ Health A 76:865–873

    CAS  Google Scholar 

  • Rochester JR (2013) Bisphenol A and human health: a review of the literature. Reprod Toxicol 42:132–155

    CAS  Google Scholar 

  • Rochester JR, Bolden AL (2015) Bisphenol S and F: A systematic review and comparison of the hormonal activity of bisphenol a substitutes. Environ Health Perspect 123:643–650

    CAS  Google Scholar 

  • Rosenmai AK, Dybdahl M, Pedersen M, Alice van Vugt-Lussenburg BM, Wedebye EB, Taxvig C, Vinggaard AM (2014) Are structural analogues to bisphenol a safe alternatives? Toxicol Sci 139:35–47

    CAS  Google Scholar 

  • Shapiro GD, Dodds L, Arbuckle TE, Ashley-Martin J, Fraser W, Fisher M, Taback S, Keely E, Bouchard MF, Monnier P, Dallaire R, Morisset A, Ettinger AS (2015) Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study. Environ Int 83:63–71

    CAS  Google Scholar 

  • Shekhar S, Sood S, Showkat S, Lite C, Chandrasekhar A, Vairamani M, Barathi S, Santosh W (2017) Detection of phenolic endocrine disrupting chemicals (EDCs) from maternal blood plasma and amniotic fluid in Indian population. Gen Comp Endocrinol 241:100–107

    CAS  Google Scholar 

  • Soriano S, Alonso-Magdalena P, García-Arévalo M, Novials A, Muhammed SJ, Salehi A, Gustafsson JA, Quesada I, Nadal A (2012) Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor β. PLoS One 7:e31109

    CAS  Google Scholar 

  • Sun Q, Cornelis MC, Townsend MK, Tobias DK, Eliassen AH, Franke AA, Hauser R, Hu FB (2014) Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses’ Health Study (NHS) and NHSII cohorts. Environ Health Perspect 122:616–623

    Google Scholar 

  • Tiano J, Mauvais-Jarvis F (2012) Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes. Islets 4:173–176

    Google Scholar 

  • Tiano JP, Delghingaro-Augusto V, Le May C, Liu S, Kaw MK, Khuder SS, Latour MG, Bhatt SA, Korach KS, Najjar SM, Prentki M, Mauvais-Jarvis F (2011) Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents β cell failure in rodent models of type 2 diabetes. J Clin Invest 121:3331–3342

    CAS  Google Scholar 

  • Valeri L, Mazumdar MM, Bobb JF, Claus Henn B, Rodrigues E, Sharif OIA, Kile ML, Quamruzzaman Q, Afroz S, Golam M, Amarasiriwardena C, Bellinger DC, Christiani DC, Coull BA, Wright RO (2017) The joint effect of prenatal exposure to metal mixtures on neurodevelopmental outcomes at 20–40 months of age: evidence from rural Bangladesh. Environ Health Perspect 125:067015

    Google Scholar 

  • Wan Y, Huo W, Xu S, Zheng T, Zhang B, Li Y, Zhou A, Zhang Y, Hu J, Zhu Y, Chen Z, Lu S, Wu C, Jiang M, Jiang Y, Liu H, Yang X, Xia W (2018) Relationship between maternal exposure to bisphenol S and pregnancy duration. Environ Pollut 238:717–724

    CAS  Google Scholar 

  • Wang X, Wang X, Chen Q, Luo ZC, Zhao S, Wang W, Zhang HJ, Zhang J, Ouyang F (2017) Urinary bisphenol a concentration and gestational diabetes mellitus in Chinese women. Epidemiology 28(Suppl 1):S41-s47

    Google Scholar 

  • Waters TP, Schultz BAH, Mercer BM, Catalano PM (2009) Effect of 17alpha-hydroxyprogesterone caproate on glucose intolerance in pregnancy. Obstet Gynecol 114:45–49

    CAS  Google Scholar 

  • Xu H, Zhou Q, Zhang J, Chen X, Zhao H, Lu H, Ma B, Wang Z, Wu C, Ying C, Xiong Y, Zhou Z, Li X (2020) Exposure to elevated per- and polyfluoroalkyl substances in early pregnancy is related to increased risk of gestational diabetes mellitus: A nested case-control study in Shanghai. China. Environ Int 143:105952

    CAS  Google Scholar 

  • Yang J, Wang H, Du H, Xu L, Liu S, Yi J, Chen Y, Jiang Q, He G (2021) Serum Bisphenol A, glucose homeostasis, and gestational diabetes mellitus in Chinese pregnant women: a prospective study. Environ Sci Pollut Res Int 28:12546–12554

    CAS  Google Scholar 

  • Zeng Q, He Y, Dong S, Zhao X, Chen Z, Song Z, Chang G, Yang F, Wang Y (2014) Optimal cut-off values of BMI, waist circumference and waist:height ratio for defining obesity in Chinese adults. Br J Nutr 112:1735–1744

    CAS  Google Scholar 

  • Zhang T, Sun H, Kannan K (2013) Blood and urinary bisphenol A concentrations in children, adults, and pregnant women from china: partitioning between blood and urine and maternal and fetal cord blood. Environ Sci Technol 47:4686–4694

    CAS  Google Scholar 

  • Zhang W, Xia W, Liu W, Li X, Hu J, Zhang B, Xu S, Zhou Y, Li J, Cai Z, Li Y (2019) Exposure to bisphenol a substitutes and gestational diabetes mellitus: a prospective cohort study in China. Front Endocrinol (lausanne) 10:262

    Google Scholar 

  • Zhao F, Jiang G, Wei P, Wang H, Ru S (2018) Bisphenol S exposure impairs glucose homeostasis in male zebrafish (Danio rerio). Ecotoxicol Environ Saf 147:794–802

    CAS  Google Scholar 

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Acknowledgements

The authors really appreciate all the participants who collaborated with this study and donated serum samples as well as all staff for assisting in collecting the samples and data.

Funding

This research was supported by Guangxi Key Research Program (AB17195012) and the National Natural Science Foundation of China (81860587).

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  1. Peng Tang and Jun Liang contributed equally to this work

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China

    Peng Tang, Jun Liang, Qian Liao, Huishen Huang, Xiaojing Guo, Bihu Liu, Bincai Wei, Xiaoyun Zeng & Xiaoqiang Qiu

  2. Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China

    Mengrui Lin & Dongping Huang

  3. Department of Maternal, Child and Adolescent Health, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China

    Shun Liu

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  1. Peng Tang
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Contributions

Peng Tang: methodology, formal analysis, writing (original draft), visualization. Jun Liang: methodology, investigation, data curation, validation. Qian Liao: methodology, validation, investigation. Huishen Huang: validation, investigation. Xiaojing Guo: validation, investigation. Mengrui Lin: investigation. Bihu Liu: investigation. Bincai Wei: investigation. Xiaoyun Zeng: writing (review and editing), supervision. Shun Liu: writing (review and editing), supervision. Dongping Huang: methodology, writing (review and editing), supervision, funding acquisition. Xiaoqiang Qiu: project administration, resources, data curation, writing (review and editing), supervision, funding acquisition.

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Correspondence to Shun Liu, Dongping Huang or Xiaoqiang Qiu.

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Tang, P., Liang, J., Liao, Q. et al. Associations of bisphenol exposure with the risk of gestational diabetes mellitus: a nested case–control study in Guangxi, China. Environ Sci Pollut Res 30, 25170–25180 (2023). https://doi.org/10.1007/s11356-021-17794-8

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