pp 1–10 | Cite as

Urinary bisphenol A concentration and glucose homeostasis in non-diabetic adults: a repeated-measures, longitudinal study

  • Bin Wang
  • Mian Li
  • Zhiyun Zhao
  • Jieli Lu
  • Yuhong Chen
  • Yu Xu
  • Min Xu
  • Weiqing Wang
  • Tiange WangEmail author
  • Yufang BiEmail author
  • Guang Ning



Bisphenol A (BPA) has been shown to be potentially associated with type 2 diabetes; however, there is little evidence associating BPA exposure with glucose metabolic outcomes prior to diabetes onset. We aimed to examine BPA exposure in relation to glucose homeostasis among non-diabetic individuals.


This longitudinal cohort study comprised 2336 Chinese adults aged 40 years or above (62.8% women) and free of diabetes at baseline in 2009, followed for 4 years. Urinary BPA and glucose metabolic traits including fasting plasma glucose (FPG), 2 h post-load plasma glucose, fasting serum insulin, HOMA-IR and HOMA-B were measured at baseline and follow-up. Repeated-measures analysis was performed to evaluate associations of urinary BPA concentration with markers of glucose homeostasis.


After full adjustment for confounders including BMI, each tenfold increase in urinary BPA concentrations was associated with a 3.39% increase in FPG (95% CI 2.24%, 4.55%) and an 11.6% decrease in HOMA-B (95% CI −15.8%, −7.18%) in women. The inverse association between urinary BPA and HOMA-B was more prominent among overweight or obese individuals (change −13.7%; 95% CI −19.3%, −7.61%) compared with those who were of normal weight (change −6.74%; 95% CI −13.2%, 0.20%) (pinteraction = 0.07). Moreover, the ORs of fasting hyperglycaemia and beta cell dysfunction corresponding to a tenfold increase in urinary BPA concentrations were 1.37 (95% CI 1.10, 1.72) and 1.30 (95% CI 1.02, 1.65) in women, respectively. No significant associations existed between urinary BPA and glucose metabolic markers in men.


Our findings suggest that exposure to BPA was independently associated with impaired glucose homeostasis before the development of diabetes in middle-aged and elderly women.


Bisphenol A Glucose homeostasis HOMA-B Repeated measures Type 2 diabetes 



Bisphenol A


Fasting plasma glucose


Generalised additive mixed models


Interquartile range


Post-load plasma glucose



The investigators are grateful to all participants for their cooperation in the study.

Contribution statement

BW, ML, TW, YB and GN contributed to the study design and concept. BW and ML analysed the data and drafted the manuscript. ZZ, JL, YC, YX, MX, WW and GN contributed to data interpretation and the editing of the manuscript. TW and YB critically revised the manuscript for important intellectual content. All authors have approved the final version to be published. TW, YB and GN guarantee this work and have full access to all of the data and take responsibility for the integrity of the data.


This work was funded by the Chinese Ministry of Finance, the 973 Foundation (grant 2015CB553601), National Key R&D Program of China (grants 2016YFC1305600, 2017YFC1310700, 2016YFC0901200 and 2016YFC1304904), National Natural Science Foundation of China (grants 81622011 and 81621061), Shanghai Pujiang Program (18PJ1409600) and Shanghai Municipal Education Commission–Gaofeng Clinical Medicine and Doctoral Innovation Grant Support from Shanghai Jiao Tong University School of Medicine (grants 20171901, 20161301, 20152508, 20161307 and BXJ201908).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2019_4898_MOESM1_ESM.pdf (180 kb)
ESM (PDF 179 kb)


  1. 1.
    GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388(10053):1545–1602. CrossRefGoogle Scholar
  2. 2.
    Qi L, Hu FB, Hu G (2008) Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes. Curr Mol Med 8(6):519–532. CrossRefPubMedGoogle Scholar
  3. 3.
    Casals-Casas C, Desvergne B (2011) Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol 73(1):135–162. CrossRefPubMedGoogle Scholar
  4. 4.
    Ruiz D, Becerra M, Jagai JS, Ard K, Sargis RM (2018) Disparities in environmental exposures to endocrine-disrupting chemicals and diabetes risk in vulnerable populations. Diabetes Care 41(1):193–205. CrossRefPubMedGoogle Scholar
  5. 5.
    Hao M, Ding L, Xuan L et al (2018) Urinary bisphenol A concentration and the risk of central obesity in Chinese adults: a prospective study. J Diabetes 10(6):442–448. CrossRefPubMedGoogle Scholar
  6. 6.
    Ehrlich S, Calafat AM, Humblet O, Smith T, Hauser R (2014) Handling of thermal receipts as a source of exposure to bisphenol A. JAMA 311(8):859–860. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lakind JS, Naiman DQ (2008) Daily intake of bisphenol A and potential sources of exposure: 2005–2006 National Health and Nutrition Examination Survey. J Expo Sci Environ Epidemiol 21(3):272–279. CrossRefGoogle Scholar
  8. 8.
    Dekant W, Volkel W (2008) Human exposure to bisphenol A by biomonitoring: methods, results and assessment of environmental exposures. Toxicol Appl Pharmacol 228(1):114–134. CrossRefPubMedGoogle Scholar
  9. 9.
    Vandenberg LN, Chahoud I, Heindel JJ, Padmanabhan V, Paumgartten FJ, Schoenfelder G (2010) Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect 118(8):1055–1070. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A (2006) The estrogenic effect of bisphenol A disrupts pancreatic β-cell function in vivo and induces insulin resistance. Environ Health Perspect 114(1):106–112. CrossRefPubMedGoogle Scholar
  11. 11.
    Ben-Jonathan N, Hugo ER, Brandebourg TD (2009) Effects of bisphenol A on adipokine release from human adipose tissue: implications for the metabolic syndrome. Mol Cell Endocrinol 304(1–2):49–54. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bindhumol V, Chitra KC, Mathur PP (2003) Bisphenol A induces reactive oxygen species generation in the liver of male rats. Toxicology 188(2–3):117–124. CrossRefGoogle Scholar
  13. 13.
    Lang IA, Galloway TS, Scarlett A et al (2008) Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 300(11):1303–1310. CrossRefGoogle Scholar
  14. 14.
    LaKind JS, Goodman M, Naiman DQ (2012) Use of NHANES data to link chemical exposures to chronic diseases: a cautionary tale. PLoS One 7(12):e51086. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Shankar A, Teppala S (2011) Relationship between urinary bisphenol A levels and diabetes mellitus. J Clin Endocrinol Metab 96(12):3822–3826. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ning G, Bi Y, Wang T et al (2011) Relationship of urinary bisphenol A concentration to risk for prevalent type 2 diabetes in Chinese adults: a cross-sectional analysis. Ann Intern Med 155(6):368–374. CrossRefPubMedGoogle Scholar
  17. 17.
    Tai X, Chen Y (2016) Urinary bisphenol A concentrations positively associated with glycated hemoglobin and other indicators of diabetes in Canadian men. Environ Res 147:172–178. CrossRefPubMedGoogle Scholar
  18. 18.
    Beydoun HA, Khanal S, Zonderman A, Beydoun MA (2014) Sex differences in the association of urinary bisphenol-A concentration with selected indices of glucose homeostasis among U.S. adults. Ann Epidemiol 24(2):90–97. CrossRefPubMedGoogle Scholar
  19. 19.
    Ye X, Wong LY, Bishop AM, Calafat AM (2011) Variability of urinary concentrations of bisphenol A in spot samples, first morning voids, and 24-hour collections. Environ Health Perspect 119(7):983–988. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Bi Y, Wang W, Xu M et al (2016) Diabetes genetic risk score modifies effect of bisphenol A exposure on deterioration in glucose metabolism. J Clin Endocrinol Metab 101(1):143–150. CrossRefGoogle Scholar
  21. 21.
    He Y, Miao M, Herrinton LJ et al (2009) Bisphenol A levels in blood and urine in a Chinese population and the personal factors affecting the levels. Environ Res 109(5):629–633. CrossRefPubMedGoogle Scholar
  22. 22.
    American Diabetes Association (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care 32(Suppl 1):S62–S67. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhou BF (2002) Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults—study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci 15(1):83–96Google Scholar
  25. 25.
    Sun Q, Cornelis MC, Townsend MK et al (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(6):616–623. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mahalingaiah S, Meeker JD, Pearson KR et al (2008) Temporal variability and predictors of urinary bisphenol A concentrations in men and women. Environ Health Perspect 116(2):173–178. CrossRefPubMedGoogle Scholar
  27. 27.
    Sabanayagam C, Teppala S, Shankar A (2013) Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes. Acta Diabetol 50(4):625–631. CrossRefPubMedGoogle Scholar
  28. 28.
    Ding EL, Song Y, Malik VS, Liu S (2006) Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295(11):1288–1299. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Liu S, Sun Q (2018) Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes. J Diabetes 10(6):428–441. CrossRefPubMedGoogle Scholar
  30. 30.
    Alonso-Magdalena P, Ropero AB, Carrera MP et al (2008) Pancreatic insulin content regulation by the estrogen receptor ERα. PLoS One 3(4):e2069. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ropero AB, Alonso-Magdalena P, García-García E, Ripoll C, Fuentes E, Nadal A (2008) Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl 31(2):194–200. CrossRefPubMedGoogle Scholar
  32. 32.
    Lin Y, Sun X, Qiu L et al (2013) Exposure to bisphenol A induces dysfunction of insulin secretion and apoptosis through the damage of mitochondria in rat insulinoma (INS-1) cells. Cell Death Dis 4(1):e460. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Song L, Xia W, Zhou Z et al (2012) Low-level phenolic estrogen pollutants impair islets morphology and β-cells function in isolated rat islets. J Endocrinol 215(2):303–311. CrossRefPubMedGoogle Scholar
  34. 34.
    Bansal A, Rashid C, Xin F et al (2017) Sex- and dose-specific effects of maternal bisphenol A exposure on pancreatic islets of first- and second-generation adult mice offspring. Environ Health Perspect 125(9):097022. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Rhodes CJ (2005) Type 2 diabetes—a matter of beta-cell life and death? Science 307(5708):380–384. CrossRefPubMedGoogle Scholar
  36. 36.
    Dales RE, Kauri LM, Cakmak S (2018) The associations between phthalate exposure and insulin resistance, β-cell function and blood glucose control in a population-based sample. Sci Total Environ 612:1287–1292. CrossRefPubMedGoogle Scholar
  37. 37.
    Lind PM, Zethelius B, Lind L (2012) Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly. Diabetes Care 35(7):1519–1524. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zota AR, Calafat AM, Woodruff TJ (2014) Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ Health Perspect 122(3):235–241. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Bin Wang
    • 1
    • 2
    • 3
  • Mian Li
    • 1
    • 2
    • 3
  • Zhiyun Zhao
    • 1
    • 2
    • 3
  • Jieli Lu
    • 1
    • 2
    • 3
  • Yuhong Chen
    • 1
    • 2
    • 3
  • Yu Xu
    • 1
    • 2
    • 3
  • Min Xu
    • 1
    • 2
    • 3
  • Weiqing Wang
    • 1
    • 2
    • 3
  • Tiange Wang
    • 1
    • 2
    • 3
    Email author
  • Yufang Bi
    • 1
    • 2
    • 3
    Email author
  • Guang Ning
    • 1
    • 2
    • 3
  1. 1.State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic DiseasesRui-Jin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Department of Endocrine and Metabolic DiseasesRui-Jin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  3. 3.Shanghai Institute of Endocrine and Metabolic DiseasesRui-Jin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina

Personalised recommendations