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Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes

Abstract

Bisphenol A (BPA) is a high volume production chemical used in the manufacture of polycarbonate plastics and epoxy resins. Recent experimental studies have suggested that BPA affects glucose metabolism through diverse mechanisms including insulin resistance, pancreatic β-cell dysfunction, adipogenesis, inflammation and oxidative stress. Prediabetes is a stage earlier in the hyperglycemia continuum associated with increased future risk of developing diabetes. Therefore, we examined the association between BPA exposure and prediabetes among subjects free of diabetes. We examined the association between urinary BPA levels and prediabetes in 3,516 subjects from the National Health and Nutritional Examination Survey 2003–2008. Urinary BPA levels were examined in tertiles. Prediabetes was defined as fasting glucose concentration 100–125 mg/dL or 2-h glucose concentration of 140–199 mg/dL or an A1C value of 5.7–6.4 %. Overall, we observed a positive association between higher levels of urinary BPA and prediabetes, independent of potential confounders including body mass index, alcohol intake, blood pressure and serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95 % confidence interval) of prediabetes associated with tertile 3 of BPA was 1.34 (1.03–1.73), p-trend = 0.02. In subgroup analysis, this association was stronger among women and obese subjects. Higher urinary BPA levels are found to be associated with prediabetes independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.

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References

  1. 1.

    Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL (2005) Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect 113:391–395

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV (2007) Human exposure to bisphenol A (BPA). Reprod Toxicol 24:139–177

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Adachi T, Yasuda K, Mori C et al (2005) Promoting insulin secretion in pancreatic islets by means of bisphenol A and nonylphenol via intracellular estrogen receptors. Food Chem Toxicol 43:713–719

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Sakurai K, Kawazuma M, Adachi T et al (2004) Bisphenol A affects glucose transport in mouse 3T3-F442A adipocytes. Br J Pharmacol 141:209–214

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A (2006) The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect 114:106–112

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Gerich JE (2003) Contributions of insulin-resistance and insulin-secretory defects to the pathogenesis of type 2 diabetes mellitus. Mayo Clin Proc 78:447–456

    PubMed  Article  Google Scholar 

  7. 7.

    Ropero AB, Alonso-Magdalena P, Garcia-Garcia E, Ripoll C, Fuentes E, Nadal A (2008) Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl 31:194–200

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Kawasaki T, Igarashi K, Ogata N, Oka Y, Ichiyanagi K, Yamanouchi T (2010) Markedly increased serum and urinary fructose concentrations in diabetic patients with ketoacidosis or ketosis. Acta Diabetol 49:119–123

    Google Scholar 

  9. 9.

    Lang IA, Galloway TS, Scarlett A et al (2008) Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 300:1303–1310

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Melzer D, Rice NE, Lewis C, Henley WE, Galloway TS (2010) Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 2003/06. PLoS ONE 5:e8673

    PubMed  Article  Google Scholar 

  11. 11.

    American Diabetes Association (2010) Standards of medical care in diabetes–2010. Diabetes 413 Care 33 (suppl 1):S11–S61

    Google Scholar 

  12. 12.

    Leiter LA (2006) From hyperglycemia to the risk of cardiovascular disease. Rev Cardiovasc Med 7(Suppl 2):S3–S9

    PubMed  Google Scholar 

  13. 13.

    Gabir MM, Hanson RL, Dabelea D et al (2000) Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes. Diabetes Care 23:1113–1118

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Schaefer C, Biermann T, Schroeder M et al (2010) Early microvascular complications of prediabetes in mice with impaired glucose tolerance and dyslipidemia. Acta Diabetol 47:19–27

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Zheng X, Ren W, Zhang S et al (2010) Serum levels of proamylin and amylin in normal subjects and patients with impaired glucose regulation and type 2 diabetes mellitus. Acta Diabetol 47:265–270

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Abdul-Ghani MA, Tripathy D, DeFronzo RA (2006) Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 29:1130–1139

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    National Center for Health Statistics (2010) 2003–2004 National Health and Nutrition Examination Survey: survey operations manuals (Article online)

  18. 18.

    National Center for Health Statistics (2010) 2005–2006 National Health and Nutrition Examination Survey: survey operations manuals (Article online)

  19. 19.

    National Center for Health Statistics (2010) 2007–2008 National Health and Nutrition Examination Survey: survey operations manuals (Article online)

  20. 20.

    National Center for Health Statistics (2010) 2003–2004 National Health and Nutrition Examination Survey: survey operations manuals (Article online). Available at: http://www.cdc.gov/nchs/nhanes/nhanes2003-2004/current_nhanes_03_04.htm. Accessed 22 April 2011

  21. 21.

    National Center for Health Statistics (2010) 2005–2006 National Health and Nutrition Examination Survey: survey operations manuals (Article online). Available at: http://www.cdc.gov/nchs/nhanes/nhanes2005-2006/current_nhanes_05_06.htm. Accessed 22 April 2011

  22. 22.

    National Center for Health Statistics (2010) 2007–2008 National Health and Nutrition Examination Survey: survey operations manuals (Article online). Available at: http://www.cdc.gov/nchs/nhanes/nhanes2007-2008/current_nhanes_07_08.htm. Accessed 22 April 2011

  23. 23.

    National Center for Health Statistics (2010) 2003–2004 National Health and Nutrition Examination Survey: Laboratory procedures (Article online). Available at: http://www.cdc.gov/nchs/nhanes/nhanes2003-2004/L24EPH_C.htm. Accessed 4 May 2011

  24. 24.

    National Center for Health Statistics (2009) 2005–2006 National Health and Nutrition Examination Survey: Environmental phenols and parabens (EPH_D). Available at: http://www.cdc.gov/nchs/nhanes/nhanes2005-2006/EPH_D.htm. Accessed 24 October 2011

  25. 25.

    Ye X, Kuklenyik Z, Needham LL, Calafat AM (2005) Automated on-line column-switching HPLC-MS/MS method with peak focusing for the determination of nine environmental phenols in urine. Anal Chem 77:5407–5413

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    National Center for Health Statistics (2010) 2003–2004 National Health and Nutrition Examination Survey: laboratory procedures (Article online)

  27. 27.

    Diagnosis and classification of diabetes mellitus. Diabetes Care 2011;34(suppl 1):S62–S69

  28. 28.

    Kehoe R, Wu SY, Leske MC, Chylack LT Jr (1994) Comparing self-reported and physician-reported medical history. Am J Epidemiol 139:813–818

    PubMed  CAS  Google Scholar 

  29. 29.

    Szklo M, Nieto FJ (2007) Epidemiology: beyond the basics

  30. 30.

    Rubin BS, Soto AM, Bisphenol A (2009) Perinatal exposure and body weight. Mol Cell Endocrinol 304:55–62

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Guo L, Cheng Y, Wang X et al (2010) Association between microalbuminuria and cardiovascular disease in type 2 diabetes mellitus of the Beijing Han nationality. Acta Diabetol 49:S65–S71

    Google Scholar 

  32. 32.

    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 304:49–54

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Bindhumol V, Chitra KC, Mathur PP (2003) Bisphenol A induces reactive oxygen species generation in the liver of male rats. Toxicology 188:117–124

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Kim MJ, Jung HS, Hwang-Bo Y et al (2011) Evaluation of 1,5-anhydroglucitol as a marker for glycemic variability in patients with type 2 diabetes mellitus. Acta Diabetol [Epub ahead of print]

  35. 35.

    Wada K, Sakamoto H, Nishikawa K et al (2007) Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome. J Pharmacol Sci 105:133–137

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Sargis RM, Johnson DN, Choudhury RA, Brady MJ (2010) Environmental endocrine disruptors promote adipogenesis in the 3T3-L1 cell line through glucocorticoid receptor activation. Obesity (Silver Spring) 18:1283–1288

    Article  CAS  Google Scholar 

  37. 37.

    Moriyama K, Tagami T, Akamizu T et al (2002) Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab 87:5185–5190

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Teeguarden JG, Calafat AM, Ye X et al (2011) Twenty-four hour human urine and serum profiles of bisphenol a during high-dietary exposure. Toxicol Sci 123:48–57

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Hengstler JG, Foth H, Gebel T et al (2011) Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A. Crit Rev Toxicol 41:263–291

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Tsukioka T, Terasawa J, Sato S, Hatayama Y, Makino T, Nakazawa H (2004) Development of analytical method for determining trace amounts of BPA in urine samples and estimation of exposure to BPA. J Environ Chem 14:57–63

    Article  CAS  Google Scholar 

  41. 41.

    Fernandez MF, Arrebola JP, Taoufiki J et al (2007) Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reprod Toxicol 24:259–264

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Nunez AA, Kannan K, Giesy JP, Fang J, Clemens LG (2001) Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats. Chemosphere 42:917–922

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Carwile JL, Michels KB (2011) Urinary bisphenol A and obesity: NHANES 2003–2006. Environ Res 111:825–830

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Thorand B, Baumert J, Kolb H et al (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30:854–860

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    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 295:1288–1299

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL (2008) Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect 116:39–44

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    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 116:173–178

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Braun JM, Kalkbrenner AE, Calafat AM et al (2011) Variability and predictors of urinary bisphenol A concentrations during pregnancy. Environ Health Perspect 119:131–137

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Pottenger LH, Domoradzki JY, Markham DA, Hansen SC, Cagen SZ, Waechter JM Jr (2000) The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration. Toxicol Sci 54:3–18

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    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 119:983–988

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    WHO/FAO Expert Panel (2011) Toxicological and Health Aspects of Bisphenol A. Available at: http://whqlibdoc.who.int/publications/2011/97892141564274_eng.pdf. Accessed 26 Sep 2011

  52. 52.

    Schulze MB, Manson JE, Ludwig DS et al (2004) Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA 292:927–934

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

This study was funded by an American Heart Association National Clinical Research Program grant (AS).

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There are no conflicts of interest related to this manuscript.

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Correspondence to Charumathi Sabanayagam.

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Sabanayagam, C., Teppala, S. & Shankar, A. Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes. Acta Diabetol 50, 625–631 (2013). https://doi.org/10.1007/s00592-013-0472-z

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Keywords

  • Bisphenol A
  • BMI
  • Gender
  • Prediabetes
  • NHANES