Abstract
Purpose
Environmental pollutant Bisphenol A (BPA) strongly interacts with insulin resistance, which leads to type 2 diabetes mellitus (T2DM). Uncontrolled glucose levels in both blood and urine develops vascular complications in T2DM patients. However, glucose-controlled diabetic patients are also affected by vascular complications due to vascular calcification, and there is a lack of clinically relevant data on BPA levels available in patients with T2DM-associated vascular complications due to vascular calcification. Therefore, we measured BPA levels in T2DM-associated vascular complications and correlated systemic BPA levels with vascular calcification-related gene expression.
Methods
This study included 120 participants with T2DM and its associated vascular complications. Serum and urinary BPA were estimated using an ELISA kit, and gene expression of the study participants in peripheral blood mononuclear cells (PBMCs) was studied with quantitative real-time PCR.
Results
Serum and urinary BPA levels were higher in T2DM and its associated vascular complications with CVD and DN patients compared to control. Both Serum and urinary BPA had higher significance with Sirt1 (p < 0.001, p < 0.001), Runx2 (p < 0.01, p < 0.001) and IL-1beta (p < 0.001, p < 0.02) gene expression in the study groups, but, TNF-alpha significant with Serum BPA (p < 0.04), not urinary BPA (p < 0.31).
Conclusion
BPA levels were positively correlated with lower Sirt1 and increased Runx2 in T2DM-associated vascular complications patients. Also, higher expression of IL-1beta and TNF-alpha was observed in T2DM-associated vascular complications patients. Our study is the first to associate BPA levels with vascular calcification in patients with T2DM and its associated vascular complications.
Similar content being viewed by others
Data availability statement
The data that support the findings of this study are available from the corresponding author, P.V., upon reasonable request.
References
Awadallah EA, Hasan NS, Awad MA, Kamel SA, Yousef RN, Musa NI, Hassan EM (2020) Associations of GCKR, TCF7L2, SLC30A8 and IGFB polymorphisms with Type 2 diabetes mellitus in Egyptian populations. Jordan J Biol Sci 13(3):383–389
Balestrieri ML, Servillo L, Esposito A, D’onofrio N, Giovane A, Casale R, Marfella R (2013) Poor glycaemic control in type 2 diabetes patients reduces endothelial progenitor cell number by influencing SIRT1 signalling via platelet-activating factor receptor activation. Diabetologia 56:162–172. https://doi.org/10.1007/s00125-012-2749-0
Baralić K, Živančević K, Jorgovanović D, Javorac D, Radovanović J, Gojković T, Đukić-Ćosić D (2021) Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: Merging bioinformatics with in vivo analysis. Food Chem Toxicol 154:112325. https://doi.org/10.1016/j.fct.2021.112325
Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, Chen Y (2008) Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem 283(22):15319–15327. https://doi.org/10.1074/jbc.M800021200
Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O, Beulens JW (2019) Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications. Eur J Prevent Cardiol 26(2):25–32. https://doi.org/10.1177/2047487319878371
Cheng YJ, Imperatore G, Geiss LS, Saydah SH, Albright AL, Ali MK, Gregg EW (2018) Trends and disparities in cardiovascular mortality among US adults with and without self-reported diabetes, 1988–2015. Diabetes Care 41(11):2306–2315. https://doi.org/10.2337/dc18-0831
Chianese R, Viggiano A, Urbanek K, Cappetta D, Troisi J, Scafuro M, Meccariello R (2018) Chronic exposure to low dose of bisphenol A impacts on the first round of spermatogenesis via SIRT1 modulation. Sci Rep 8(1):2961. https://doi.org/10.1038/s41598-018-21076-8
Cimmino I, Fiory F, Perruolo G, Miele C, Beguinot F, Formisano P, Oriente F (2020) Potential mechanisms of bisphenol A (BPA) contributing to human disease. Int J Mol Sci 21(16):5761. https://doi.org/10.3390/ijms21165761
Corkum CP, Ings DP, Burgess C, Karwowska S, Kroll W, Michalak TI (2015) Immune cell subsets and their gene expression profiles from human PBMC isolated by vacutainer cell preparation tube (CPT™) and standard density gradient. BMC Immunol 16(1):1–18. https://doi.org/10.1186/s12865-015-0113-0
González-González JG, Violante-Cumpa JR, Zambrano-Lucio M, Burciaga-Jimenez E, Castillo-Morales PL, Garcia-Campa M, Rodríguez-Gutiérrez R (2022) HOMA-IR as a predictor of health outcomes in patients with metabolic risk factors: a systematic review and meta-analysis. High Blood Press Cardiovasc Prev 29(6):547–564. https://doi.org/10.1007/s40292-022-00542-5
Hoogeveen EK (2022) The epidemiology of diabetic kidney disease. Kidney Dial 2(3):433–442. https://doi.org/10.3390/kidneydial2030038
Htay T, Soe K, Lopez-Perez A, Doan AH, Romagosa MA, Aung K (2019) Mortality and cardiovascular disease in type 1 and type 2 diabetes. Curr Cardiol Rep 21:1–7. https://doi.org/10.1007/s11886-019-1133-9
Hwang S, Lim JE, Choi Y, Jee SH (2018) Bisphenol A exposure and type 2 diabetes mellitus risk: a meta-analysis. BMC Endocr Disord 18(1):1–10. https://doi.org/10.1186/s12902-018-0310-y
Jalgaonkar MP, Parmar UM, Kulkarni YA, Oza MJ (2022) SIRT1-FOXOs activity regulates diabetic complications. Pharmacol Res 175:106014. https://doi.org/10.1016/j.phrs.2021.106014
Jia Y, Zheng Z, Wang Y, Zhou Q, Cai W, Jia W, Hu D (2015) SIRT1 is a regulator in high glucose-induced inflammatory response in RAW264. 7 cells. PLoS One 10(3):e0120849. https://doi.org/10.1371/journal.pone.0120849
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85(7):2402–2410. https://doi.org/10.1210/jcem.85.7.6661
Keshavarz-Maleki R, Kaviani A, Omranipour R, Gholami M, Khoshayand MR, Ostad SN, Sabzevari O (2021) Bisphenol-A in biological samples of breast cancer mastectomy and mammoplasty patients and correlation with levels measured in urine and tissue. Sci Rep 11(1):18411. https://doi.org/10.1038/s41598-021-97864-6
Lin ME, Chen T, Leaf EM, Speer MY, Giachelli CM (2015) Runx2 expression in smooth muscle cells is required for arterial medial calcification in mice. Am J Pathol 185(7):1958–1969. https://doi.org/10.1016/ajpath.2015.03.020
Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M (2016) Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokine 86:100–109. https://doi.org/10.1016/j.cyto.2016.06.028
Meng T, Qin W, Liu B (2020) SIRT1 antagonizes oxidative stress in diabetic vascular complication. Front Endocrinol 11:568861. https://doi.org/10.3389/fendo.2020.568861
Mihanfar A, Akbarzadeh M, Ghazizadeh Darband S, Sadighparvar S (2021) Majidinia, M (2021) SIRT1: A promising therapeutic target in type 2 diabetes mellitus. Arch Physiol Biochem. https://doi.org/10.1080/13813455.2021.1956976
Oladipe TT, Uadia PO (2022) Occupational exposure to bisphenol A (BPA) is a risk factor for coronary heart disease. J Health Sci 12(1):1–6. https://doi.org/10.5923/j.health.20221201.01
Papalou O, Kandaraki EA, Papadakis G, Diamanti-Kandarakis E (2019) Endocrine disrupting chemicals: an occult mediator of metabolic disease. Front Endocrinol 10:112. https://doi.org/10.3389/fendo.2019.00112
Phadwal K, Koo E, Jones RA, Forsythe RO, Tang K, Tang Q, MacRae VE (2022) Metformin protects against vascular calcification through the selective degradation of Runx2 by the p62 autophagy receptor. J Cell Physiol 237(11):4303–4316. https://doi.org/10.1002/jcp.30887
Shankar A, Teppala S, Sabanayagam C (2012) Bisphenol A and peripheral arterial disease: results from the NHANES. Environ Health Perspect 120(9):1297–1300. https://doi.org/10.1289/ehp.1104114
Sun Y, Byon CH, Yuan K, Chen J, Mao X, Heath JM, Chen Y (2012) Smooth muscle cell–specific Runx2 deficiency inhibits vascular calcification. Circul Res 111(5):543–552. https://doi.org/10.1161/CIRCRESAHA.112.267237
Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Magliano DJ (2022) IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 183:109119. https://doi.org/10.1016/j.diabres.2021.109119
Wade M, Delawder V, Reneau P, Dos Santos JM (2020) The effect of BPA exposure on insulin resistance and type 2 diabetes–The impact of muscle contraction. Medl Hypotheses 140:109675. https://doi.org/10.1016/j.mehy.2020.109675
Xu H, Jia Y, Sun Z, Su J, Liu QS, Zhou Q, Jiang G (2022) Environmental pollution, a hidden culprit for health issues. Eco-Environ Health. https://doi.org/10.1016/j.eehl.2022.04.003
Yin DQ, Hu SQ, Ying GU, Li WEI, Liu SS, Zhang AQ (2007) Immunotoxicity of bisphenol A to Carassius auratus lymphocytes and macrophages following in vitro exposure. J Environ Sci 19(2):232–237. https://doi.org/10.1016/S1001-0742(07)60038-2
Zainabadi K, Liu CJ, Guarente L (2017) SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2. PLoS One 12(5):e0178520
Zhu D, Mackenzie NC, Farquharson C, MacRae VE (2012) Mechanisms and clinical consequences of vascular calcification. Front Endocrinol 3:95. https://doi.org/10.3389/fendo.2012.00095
Acknowledgements
The authors express our sincere gratitude to SRM institute for financial support in our project.
Author information
Authors and Affiliations
Contributions
NM: Conceptualization, Resources, Writing the original draft, Writing-review & editing, and Visualization. SP: Methodology, Data curation. PR: Methodology, Investigation. GV: Visualization. VMV: Draft editing. JR: Formal analysis. PV: Supervision, Project administration, Visualization.
Corresponding author
Ethics declarations
Conflict of interest
No potential conflict of interest was reported by the author(s).
Ethical approval
The SRM institutional ethical committee was approved this study (2364/IEC/2021).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Mohanraj, N., Prasanth, S., Rajapriya, P. et al. Bisphenol A accelerates the vascular complications in patients with Type 2 diabetes mellitus through vascular calcification—a molecular approach. Int Arch Occup Environ Health 96, 1291–1299 (2023). https://doi.org/10.1007/s00420-023-02007-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00420-023-02007-1