Skip to main content
SpringerLink
Log in

Effect of glycemic control and duration of type 2 diabetes on circulatory miR-146a in middle-aged Indians

  • Original Article
  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Background

Early onset of type 2 diabetes mellitus (T2DM) may increase the risk of accelerated diabetes complications and age-related pathologies among relatively young Indians. Inflamm-miR-146a exerts a pivotal role in ageing and diabetes-associated complexities. Hence, we aimed to determine the expression of circulatory miR-146a in the plasma samples of the middle-aged (31–50 years) Indians with T2DM.

Methods

The serological markers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte-chemoattractant protein-1 (MCP-1) were measured in T2DM patients (n = 30) and healthy controls (n = 30). MiR-146a expression was determined by quantitative PCR (qPCR).

Results

Among the serological inflammatory markers, hs-CRP and IL-6 differed significantly between T2DM patients and controls. MiR-146a was found to upregulate significantly (p = 0.041) in T2DM patients than controls. Overexpression of plasma miR-146a was also observed with poor glycemia and with the longer duration of T2DM.

Conclusion

Significant upregulation of plasma miR-146a indicated the increased risk of age-related pathologies in the middle-aged T2DM patients, which might allow taking effective therapeutic or lifestyle modification measures at an early stage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data will be made available on request.

Code availability

Not applicable.

References

  1. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl_1):S4-9. https://doi.org/10.1093/gerona/glu057.

    Article  PubMed  Google Scholar 

  2. Fulop T, Witkowski JM, Olivieri F, Larbi A. The integration of inflammaging in age-related diseases. Semin Immunol. 2018;40:17–35. https://doi.org/10.1016/j.smim.2018.09.003.

    Article  CAS  PubMed  Google Scholar 

  3. Panahi G, Pasalar P, Zare M, Rizzuto R, Meshkani R. High glucose induces inflammatory responses in HepG2 cells via the oxidative stress-mediated activation of NF-κB, and MAPK pathways in HepG2 cells. Arch Physiol Biochem. 2018;124(5):468–74. https://doi.org/10.1080/13813455.2018.1427764.

    Article  CAS  PubMed  Google Scholar 

  4. Aguayo-Mazzucato C, van Haaren M, Mruk M, Lee TB Jr, Crawford C, Hollister-Lock J, Sullivan BA, Johnson JW, Ebrahimi A, Dreyfuss JM, Van Deursen J. β cell aging markers have heterogeneous distribution and are induced by insulin resistance. Cell Metab. 2017;25(4):898–910. https://doi.org/10.1016/j.cmet.2017.03.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Banerjee J, Dhas Y, Mishra N. Middle-aged Indians with type 2 diabetes are at higher risk of biological ageing with special reference to serum CDKN2A. J Diabetes Res. 2020;2020. https://doi.org/10.1155/2020/7569259

  6. Banerjee J, Roy S, Dhas Y, Mishra N. Senescence-associated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes. Clin Exp Med. 2020;20(1):149–58. https://doi.org/10.1007/s10238-019-00593-4.

    Article  CAS  PubMed  Google Scholar 

  7. Williams J, Smith F, Kumar S, Vijayan M, Reddy PH. Are microRNAs true sensors of ageing and cellular senescence? Ageing Res Rev. 2017;35:350–63. https://doi.org/10.1016/j.arr.2016.11.008.

    Article  CAS  PubMed  Google Scholar 

  8. Li J, Jiang X, Wang K. Exosomal miRNA: an alternative mediator of cell-to-cell communication. ExRNA. 2019;1(1):1–6. https://doi.org/10.1186/s41544-019-0025-x.

    Article  Google Scholar 

  9. Weber JA, Baxter DH, Zhang S, Huang DY, How Huang K, Jen Lee M, Galas DJ, Wang K. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41. https://doi.org/10.1373/clinchem.2010.147405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Olivieri F, Rippo MR, Procopio AD, Fazioli F. Circulating inflamma-miRs in aging and age-related diseases. Front Genet. 2013;4:121. https://doi.org/10.3389/fgene.2013.00121.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci. 2006;103(33):12481–6. https://doi.org/10.1073/pnas.0605298103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mensà E, Giuliani A, Matacchione G, Gurău F, Bonfigli AR, Romagnoli F, De Luca M, Sabbatinelli J, Olivieri F. Circulating miR-146a in healthy aging and type 2 diabetes: age-and gender-specific trajectories. Mech Ageing Dev. 2019;180:1–10. https://doi.org/10.1016/j.mad.2019.03.001.

    Article  CAS  PubMed  Google Scholar 

  13. Sosale B, Sosale AR, Mohan AR, Kumar PM, Saboo B, Kandula S. Cardiovascular risk factors, micro and macrovascular complications at diagnosis in patients with young onset type 2 diabetes in India: CINDI 2. Indian J Endocrinol Metab. 2016;20(1):114. https://doi.org/10.4103/2230-8210.172277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Supplement 1):S11-24. https://doi.org/10.2337/dc17-S005.

    Article  Google Scholar 

  15. Banerjee J, Mishra N, Damle G, Dhas Y. Beyond LDL-c: The importance of serum oxidized LDL in predicting risk for type 2 diabetes in the middle-aged Asian Indians. Diabetes Metab Syndr: Clin Res Rev. 2019;13(1):206–13. https://doi.org/10.1016/j.dsx.2018.08.036.

    Article  Google Scholar 

  16. Li X, Khanna A, Li N, Wang E. Circulatory miR-34a as an RNA-based, noninvasive biomarker for brain aging. Aging (Albany NY). 2011;3(10):985. https://doi.org/10.18632/aging.100371.

    Article  CAS  PubMed  Google Scholar 

  17. Smith-Vikos T, Liu Z, Parsons C, Gorospe M, Ferrucci L, Gill TM, Slack FJ. A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA). Aging (Albany NY). 2016;8(11):2971. https://doi.org/10.18632/aging.101106.

    Article  CAS  PubMed  Google Scholar 

  18. Rong Y, Bao W, Shan Z, Liu J, Yu X, Xia S, Gao H, Wang X, Yao P, Hu FB, Liu L. Increased microRNA-146a levels in plasma of patients with newly diagnosed type 2 diabetes mellitus. PLoS ONE. 2013;8(9):e73272. https://doi.org/10.1371/journal.pone.0073272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Seyhan AA, Lopez YO, Xie H, Yi F, Mathews C, Pasarica M, Pratley RE. Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study. Sci Rep. 2016;6(1):1–5. https://doi.org/10.1038/srep31479.

    Article  CAS  Google Scholar 

  20. Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, Dong Q, Pang Z, Guan Q, Gao L, Zhao J. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61–9. https://doi.org/10.1007/s00592-010-0226-0.

    Article  CAS  PubMed  Google Scholar 

  21. McMillan DH, Woeller CF, Thatcher TH, Spinelli SL, Maggirwar SB, Sime PJ, Phipps RP. Attenuation of inflammatory mediator production by the NF-κB member RelB is mediated by microRNA-146a in lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2013;304(11):L774–81. https://doi.org/10.1152/ajplung.00352.2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, Soufi FG. Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep. 2013;40(11):6477–83. https://doi.org/10.1007/s11033-013-2763-4.

    Article  CAS  PubMed  Google Scholar 

  23. Roggli E, Britan A, Gattesco S, Lin-Marq N, Abderrahmani A, Meda P, Regazzi R. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic β-cells. Diabetes. 2010;59(4):978–86. https://doi.org/10.2337/db09-0881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V. Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes. Mol Cell Biochem. 2011;351(1):197–205. https://doi.org/10.1007/s11010-011-0727-3.

    Article  CAS  PubMed  Google Scholar 

  25. Wang G, Huang Y, Wang LL, Zhang YF, Xu J, Zhou Y, Lourenco GF, Zhang B, Wang Y, Ren RJ, Halliday GM. MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer’s disease. Sci Rep. 2016;6(1):1–2. https://doi.org/10.1038/srep26697.

    Article  CAS  Google Scholar 

  26. Huang W, Tian SS, Hang PZ, Sun C, Guo J, Du ZM. Combination of microRNA-21 and microRNA-146a attenuates cardiac dysfunction and apoptosis during acute myocardial infarction in mice. Mol Ther Nucleic Acids. 2016;5:e296. https://doi.org/10.1038/mtna.2016.12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Olivieri F, Lazzarini R, Recchioni R, Marcheselli F, Rippo MR, Di Nuzzo S, Albertini MC, Graciotti L, Babini L, Mariotti S, Spada G. MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling. Age. 2013;35(4):1157–72. https://doi.org/10.1007/s11357-012-9440-8.

    Article  CAS  PubMed  Google Scholar 

  28. Guo W, Li XN, Li J, Lu J, Wu J, Zhu WF, Qin P, Xu NZ, Zhang Q. Increased plasma miR-146a levels are associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus. J Diabetes Complications. 2020;34(12):107725. https://doi.org/10.1016/j.jdiacomp.2020.107725.

    Article  PubMed  Google Scholar 

  29. Baldeón RL, Weigelt K, De Wit H, Ozcan B, van Oudenaren A, Sempertegui F, Sijbrands E, Grosse L, Freire W, Drexhage HA, Leenen PJ. Decreased serum level of miR-146a as sign of chronic inflammation in type 2 diabetic patients. PLoS ONE. 2014;9(12):e115209. https://doi.org/10.1371/journal.pone.0115209.

    Article  CAS  Google Scholar 

  30. Yan ST, Li CL, Tian H, Li J, Pei Y, Liu Y, Gong YP, Fang FS, Sun BR. MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4. Mol Cellular Biochem. 2014;397(1):45–51. https://doi.org/10.1007/s11010-014-2170-8.

    Article  CAS  Google Scholar 

  31. Kanigur Sultuybek G, Soydas T, Yenmis G. NF-κB as the mediator of metformin’s effect on ageing and ageing-related diseases. Clin Exp Pharmacol Physiol. 2019;46(5):413–22. https://doi.org/10.1111/1440-1681.13073.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We extend our thanks to Dr. Vinaykumar Rale, Director, Symbiosis School of Biological Sciences, for supporting throughout this work. We extend our gratitude to Symbiosis Centre for Research and Innovation for providing with necessary financial assistance. We also extend our sincere thanks to Symbiosis Centre for Health Care and Symbiosis Community Outreach Programme and Extension for helping in sample collection. However, this research work did not receive any specific grant from funding agencies including public, commercial or not-for-profit sectors.

Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, India

    Joyita Banerjee, Yogita Dhas, Swagata Roy & Neetu Mishra

Authors
  1. Joyita Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yogita Dhas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Swagata Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Neetu Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neetu Mishra.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Independent Ethics Committee of Symbiosis International (Deemed University), Pune.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Banerjee, J., Dhas, Y., Roy, S. et al. Effect of glycemic control and duration of type 2 diabetes on circulatory miR-146a in middle-aged Indians. Int J Diabetes Dev Ctries 43, 829–834 (2023). https://doi.org/10.1007/s13410-022-01157-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-022-01157-1

Keywords

Search

Navigation