Abstract
Objectives
Hyperglycaemia-induced inflammation plays a vital role in the development of diabetic peripheral neuropathy (DPN). Recent evidences had reported the involvement of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) in diabetic experimental models. So, this pilot study aimed to evaluate serum NF-κB levels in DPN patients.
Methods
We recruited 50 T2DM patients, of which 25 were T2DM with neuropathy and 25 were T2DM without neuropathy. In all the participants peripheral neuropathy was diagnosed based on Total neuropathy score (TNS). Serum NF-κB levels were measured by ELISA.
Results
We observed that the serum NF-κB levels were higher in DPN patients in comparison to T2DM patients without neuropathy. On spearman correlation, a positive correlation was found between serum NF-κB levels and TNS in the DPN group (r=0.741, p<0.001). The regression model shows the TNS to be an independent determinant of serum NF-κB levels after adjustment for potential confounders like age, duration of diabetes, and HbA1C (B=81.34; p<0.001).
Conclusions
NF-κB activation plays a key role in promoting inflammation which is associated with the progression of DPN. In this respect, the study of NF-κB levels in serum may be an additional diagnostic marker for DPN.
Funding source: All India Institute of Medical Sciences, Bhubaneswar
Award Identifier / Grant number: IMF/37/2018
Acknowledgments
We thank our technical staff for extending their support throughout the project. We sincerely express our gratitude to All India Institute of Medical Sciences, Bhubaneswar for funding our project.
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Research ethics: The approval was obtained from Institute Ethics Committee for human studies with reference no. T/IM-F/18-19/16 before the commencement of the study.
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References.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Research funding: This study was funded by All India Institute of Medical Sciences, Bhubaneswar funding agency with project code No. IMF/37/2018.
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Data availability: The raw data can be obtained on request from the correspondoing author.
References
1. Guariguata, L, Whiting, DR, Hambleton, I, Beagley, J, Linnenkamp, U, Shaw, JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103:137–49. https://doi.org/10.1016/j.diabres.2013.11.002.Search in Google Scholar PubMed
2. Nathan, DM. Long-term complications of diabetes mellitus. N Engl J Med 1993;328:1676–85. https://doi.org/10.1056/nejm199306103282306.Search in Google Scholar PubMed
3. Bansal, V, Kalita, J, Misra, UK. Diabetic neuropathy. Postgrad Med 2006;82:95–100. https://doi.org/10.1136/pgmj.2005.036137.Search in Google Scholar PubMed PubMed Central
4. Tesfaye, S, Selvarajah, D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev 2012;28:8–14. https://doi.org/10.1002/dmrr.2239.Search in Google Scholar PubMed
5. Hansen, S, Ballantyne, JP. Axonal dysfunction in the neuropathy of diabetes mellitus: a quantitative electrophysiological study. J Neurol Neurosurg Psychiatry 1977;40:555–64. https://doi.org/10.1136/jnnp.40.6.555.Search in Google Scholar PubMed PubMed Central
6. Allen, MD, Kimpinski, K, Doherty, TJ, Rice, CL. Length dependent loss of motor axons and altered motor unit properties in human diabetic polyneuropathy. Clin Neurophysiol 2014;125:836–43. https://doi.org/10.1016/j.clinph.2013.09.037.Search in Google Scholar PubMed
7. King, P, Peacock, I, Donnelly, R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol 1999;48:643–8. https://doi.org/10.1046/j.1365-2125.1999.00092.x.Search in Google Scholar PubMed PubMed Central
8. Edwards, JL, Vincent, AM, Cheng, HT, Feldman, EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther 2008;120:1–34. https://doi.org/10.1016/j.pharmthera.2008.05.005.Search in Google Scholar PubMed PubMed Central
9. Jin, HY, Park, TS. Role of inflammatory biomarkers in diabetic peripheral neuropathy. J Diabetes Investig 2018;9:1016–8. https://doi.org/10.1111/jdi.12794.Search in Google Scholar PubMed PubMed Central
10. Ganesh Yerra, V, Negi, G, Sharma, SS, Kumar, A. Potential therapeutic effects of the simultaneous targeting of the Nrf2 and NF-κB pathways in diabetic neuropathy. Redox Biol 2013;1:394–7. https://doi.org/10.1016/j.redox.2013.07.005.Search in Google Scholar PubMed PubMed Central
11. Javed, S, Alam, U, Malik, RA. Treating diabetic neuropathy: present strategies and emerging solutions. Rev Diabet Stud 2015;12:63–83. https://doi.org/10.1900/rds.2015.12.63.Search in Google Scholar
12. Yousefzadeh, N, Alipour, MR, Ghadiri Soufi, F. Deregulation of NF-кB–miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. J Physiol Biochem 2015;71:51–8. https://doi.org/10.1007/s13105-014-0378-4.Search in Google Scholar PubMed
13. Seyit, D, Degirmenci, E, Oguzhanoglu, A. Evaluation of electrophysiological effects of melatonin and alpha lipoic acid in rats with streptozotocine induced diabetic neuropathy. Exp Clin Endocrinol Diabetes 2016;124:300–6. https://doi.org/10.1055/s-0042-103750.Search in Google Scholar PubMed
14. Negi, G, Kumar, AS, Sharma, S. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. Curr Neurovascular Res 2011;8:294–304. https://doi.org/10.2174/156720211798120972.Search in Google Scholar PubMed
15. Park, H, Lee, J-H, Sim, JH, Park, J, Choi, S-S, Leem, JG. Effects of curcumin treatment in a diabetic neuropathic pain model of rats: involvement of c-jun N-terminal kinase located in the astrocytes and neurons of the dorsal root ganglion. In: Valença, MM, editor. Pain Res Manag, vol 2021; 2021:1–9 pp.10.1155/2021/8787231Search in Google Scholar PubMed PubMed Central
16. Issar, T, Arnold, R, Kwai, NCG, Pussell, BA, Endre, ZH, Poynten, AM, et al.. The utility of the Total Neuropathy Score as an instrument to assess neuropathy severity in chronic kidney disease: a validation study. Clin Neurophysiol 2018;129:889–94. https://doi.org/10.1016/j.clinph.2018.02.120.Search in Google Scholar PubMed
17. Tavee, J. Nerve conduction studies: basic concepts. Handb Clin Neurol 2019;160:217–24. https://doi.org/10.1016/B978-0-444-64032-1.00014-X.Search in Google Scholar PubMed
18. Cox, AA, Sagot, Y, Hedou, G, Grek, C, Wilkes, T, Vinik, AI, et al.. Low-dose pulsatile interleukin-6 as a treatment option for diabetic peripheral neuropathy. Front Endocrinol 2017;8:89. https://doi.org/10.3389/fendo.2017.00089.Search in Google Scholar PubMed PubMed Central
19. Baum, P, Toyka, KV, Blüher, M, Kosacka, J, Nowicki, M. Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy (DN)—new aspects. Int J Mol Sci 2021;22:10835. https://doi.org/10.3390/ijms221910835.Search in Google Scholar PubMed PubMed Central
20. Lawrence, T. The nuclear factor NF- B pathway in inflammation. Cold Spring Harbor Perspect Biol 2009;1:a001651. https://doi.org/10.1101/cshperspect.a001651.Search in Google Scholar PubMed PubMed Central
21. Liu, T, Zhang, L, Joo, D, Sun, S-C. NF-κB signaling in inflammation. Signal Transduct Targeted Ther 2017;2:17023. https://doi.org/10.1038/sigtrans.2017.23.Search in Google Scholar PubMed PubMed Central
22. Feng, Y, Chen, L, Luo, Q, Wu, M, Chen, Y, Shi, X. Involvement of microRNA-146a in diabetic peripheral neuropathy through the regulation of inflammation. Drug Des Dev Ther 2018;12:171–7. https://doi.org/10.2147/dddt.s157109.Search in Google Scholar
23. Oeckinghaus, A, Ghosh, S. The NF- B family of transcription factors and its regulation. Cold Spring Harbor Perspect Biol 2009;1:a000034.10.1101/cshperspect.a000034Search in Google Scholar PubMed PubMed Central
24. Nowotny, K, Jung, T, Höhn, A, Weber, D, Grune, T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules 2015;5:194–222. https://doi.org/10.3390/biom5010194.Search in Google Scholar PubMed PubMed Central
25. Cornblath, DR, Chaudhry, V, Carter, K, Lee, D, Seysedadr, M, Miernicki, M, et al.. Total neuropathy score: validation and reliability study. Neurology 1999;53:1660–4. https://doi.org/10.1212/wnl.53.8.1660.Search in Google Scholar PubMed
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Articles in the same Issue
- Frontmatter
- Original Articles
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- Comparative study of radioprotective effects of endurance training in irradiation-induced nephropathy of rat model
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