Skip to main content

Fas-mediated apoptosis and peripheral polyneuropathy in type 2 diabetes mellitus

Abstract

Objective

To evaluate the role of soluble Fas (sFas) and soluble Fas ligand (sFasL) in the pathogenesis of distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus, and to analyze the relationship between these apoptotic markers with clinical parameters and electrophysiologic profile of DSPN, as well as with different diabetic factors among those patients.

Patients and methods

The study included 60 Egyptians with type 2 diabetes mellitus. All patients were evaluated clinically for DSPN by using Michigan Neuropathy Screening Instrument. Electrophysiological diagnosis of DSPN was based on the criteria suggested by the European Standardized Telematic tool to Evaluate Electrodiagnostic Methods group. Diabetic patients were divided into two groups according to the electrophysiological findings: group A included patients with DSPN (N=42), and group B included patients without DSPN (N=18). The severity of DSPN among group A patients was assessed clinically using Toronto Clinical Neuropathy Score and electrophysiologically by the severity score proposed by Hidasi and colleagues. The study also included 30 healthy volunteers as a control group. Serum levels of sFas and sFasL were assessed in all the studied groups.

Results

Serum level of sFas was significantly elevated in diabetic patients with DSPN compared with diabetics without DSPN and nondiabetic control (P=0.029 and 0.000). Receiver operating characteristic (ROC) curve analysis detected that sFas was statistically significant in discriminating between diabetic patients with DSPN from those patients without DSPN with an accuracy of 66%. The cutoff point that has the highest sensitivity (61%) and specificity (62%) was 33.3 ng/ml. Serum level of sFas showed a positive significant correlation with the electrophysiological severity of DSPN (P=0.020). Serum level of sFasL did not show statistically significant difference between all the studied groups.

Conclusion

Fas-mediated apoptosis has an important role in the development of diabetic DSPN and is correlated with its electrophysiological severity.

References

  1. Maruthur NM. The growing prevalence of type 2 diabetes: increased incidence or improved survival? Curr Diab Rep 2013; 13:786–794.

    Article  CAS  Google Scholar 

  2. World Health Organization (WHO). Global status report on non-communicable diseases 2010. Geneva: WHO; 2011.

    Google Scholar 

  3. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87:4–14.

    Article  CAS  Google Scholar 

  4. Seung HK, Yun Cha B. Diabetic peripheral neuropathy in type 2 diabetes mellitus in Korea. Diabetes Metab J 2012; 36:6–12.

    Article  Google Scholar 

  5. Manouk B, Charles A. Prevalence and complications of diabetes mellitus in Northern Africa, a systematic review. BMC Public Health 2013; 13:387.

    Article  Google Scholar 

  6. Smith SC, Lamping DL, Maclaine GD. Measuring health-related quality of life in diabetic peripheral neuropathy: a systematic review. Diabetes Res Clin Pract 2012; 96:261–270.

    Article  CAS  Google Scholar 

  7. Shi X, Chen Y, Nadeem L, Xu G. Beneficial effect of TNF-α inhibition on diabetic peripheral neuropathy. J Neuroinflammation 2013; 10:69.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Hinder LM, Vincent AM, Burant CF, Pennathur S, Feldman EL. Bioenergetics in diabetic neuropathy: what we need to know. J Peripher Nerv Syst 2012; 17:10–14.

    Article  CAS  Google Scholar 

  9. Cosson E, Bringuier AF, Paries J, Guillot R, Vaysse J, Attali JR, et al. Fas/ Fas-ligand pathway is impaired in patients with type 2 diabetes.Influence of hypertension and insulin resistance. Diabetes Metab 2005; 31:47–54.

    Article  CAS  Google Scholar 

  10. Nat R, Radu E, Regalia T, Popescu LM. Apoptosis in human embryo development: Fas induced apoptosis in brain primary cultures. J Cell Mol Med 2001; 5:417–428.

    Article  CAS  Google Scholar 

  11. Toyozaki T, Hiroe M, Saito T. Levels of soluble Fas in patients with myocarditis, heart failure of unknown origin, and in healthy volunteers. Am J Cardiol 1998; 81:798–800.

    Article  CAS  Google Scholar 

  12. Al-Rouq F. Nerve conduction study and Fas mediated apoptosis of nerve cells in peripheral neuropathy in type 2 diabetes. Int J Diab Mellitus 2009; 1:38–39.

    Article  Google Scholar 

  13. Wernig F, XuQ. Mechanical stress-induced apoptosis in the cardiovascular system. Prog Biophys Mol Biol 2002; 78:105–137.

    Article  CAS  Google Scholar 

  14. Diagnosis and Classification of Diabetes Mellitus. American Diabetes Association. Diabetes Care 2014; 37:81–90.

    Article  Google Scholar 

  15. Mete T, Aydin Y, Saka M, Yavuz HC, Bilen S, Yalcin Y, et al. comparison of efficiencies of Michigan neuropathy screening instrument, neurothesiometer, and electromyography for diagnosis of diabetic neuropathy. Int J Endocrinol 2013; 2013:821745.

    Article  Google Scholar 

  16. Oh SJ. Clinical electromyography: nerve conduction studies. Balitmore: University Park Press; 1984.

    Google Scholar 

  17. Tankisi H, Pugdahl K, Fuglsang-Frederiksen A, Johnsen B, de Carvalho M, Fawcett PR, et al. Pathophysiology inferred from electrodiagnostic nerve tests and classification of polyneuropathies. Suggested guidelines. Clin Neurophysiol 2005; 116:1571–1580.

    Article  Google Scholar 

  18. Bril V, Perkins BA. Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care 2002; 25:2048–2052.

    Article  Google Scholar 

  19. Hidasi E, Dioszeghy P, Fulesdi B, Mechler F. Electroneurographic examinations in insulin- and non-insulin dependent diabetes mellitus. Electroencephalogr Clin Neurophysiol 1996; 99:303.

    Article  Google Scholar 

  20. Knowles WJ, Haigh WB. Amonoclonal antibody-based immunoassay for HbA1c. Diabetes 1986; 35:94.

    Google Scholar 

  21. Guillot R, Bringuier AF, Porokhov B, Guillausseau PJ, Feldmann G. Increased levels of soluble Fas in serum from diabetic patients with neuropathy. Diabetes Metab 2001; 27:315–321.

    CAS  PubMed  Google Scholar 

  22. Nisar M, Asad A, Waqas A, Ali N, Nisar A, Qayyum MA, et al. Association of diabetic neuropathy with duration of type 2 diabetes and glycemic control. Cureus 2015; 7:e302.

    PubMed  PubMed Central  Google Scholar 

  23. Kasim K, Amar M, ElSadek AA, Abdel Gawad S. Peripheral neuropathy in type-II diabetic patients attending diabetic clinics in Al-Azhar University Hospitals, Egypt. Int J Diab Mellitus 2009; 2:20–23.

    Article  Google Scholar 

  24. Abougalambou SS, Abougalambou AS. Explorative study on diabetes neuropathy among type II diabetic patients in Universiti Sains Malaysia Hospital. Diab Metab Syndr 2012; 6:167–172.

    Article  Google Scholar 

  25. Kamel SR, Hamdy M, Abo Omar HA, Kamal A, Ali LH, Abd Elkarim AH. Clinical diagnosis of distal diabetic polyneuropathy using neurological examination scores: correlation with nerve conduction studies. Egypt Rheumatol Rehabil 2015; 42:128–136.

    Article  Google Scholar 

  26. Kovac B, Emedi SM, Svalina S, Demarin V. Clinical and electrophysiological signs of diabetic polyneuropathy, the effect of glycemia and duration of diabetes mellitus. Acta Clin Croat 2011; 50:149–157.

    PubMed  Google Scholar 

  27. Zakareia FA. Electrophysiological changes, plasma vascular endothelial growth factor, fatty acid synthase, and adhesion molecules in diabetic neuropathy. Neurosciences 2008; 13:374–379.

    PubMed  Google Scholar 

  28. Smith D, Sieg S, Kaplan D. Technical note: aberrant detection of cell surface Fas ligand with anti-peptide antibodies. J Immunol. 1998; 160:4159–4600.

    CAS  PubMed  Google Scholar 

  29. Faubion WA, Guicciardi ME, Miyoshi H,Bronk SF, Roberts PJ, Svingen PA, et al. Toxic bile alts induce rodent hepatocyte apoptosis via direct activation of Fas. J Clin Invest. 1999; 103:137–145.

    Article  CAS  Google Scholar 

  30. Mondal A, Sen S, Chanda D, Kundu S, Chatterjee M, Mukherjee S. Evaluation of diabetic polyneuropathy in type 2 diabetes mellitus by nerve conduction study and association of severity of neuropathy with serum sFasL level. Indian J Endocrinol Metab 2012; 16:465–467.

    Google Scholar 

  31. Hamid SM, Shani WS. Association of sFas and sFas ligand with progression of type 2 diabetes mellitus in Basrah province. Med J Babylon 2018; 15:135–138.

    Google Scholar 

  32. Maedler K, Spinas G, Lehmann R, Sergeev P, Weber M, Fontana A, et al. Glucose induces b-cell apoptosis via upregulation of the fas receptor in human islets. Diabetes 2001; 50:1683–1690.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marwa R. Abd Elfadeel Master Degree of Physical Medicine.

Additional information

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abd Elhameed, M.M., Elsawy, N.A., Mgalaa, M.H.Z. et al. Fas-mediated apoptosis and peripheral polyneuropathy in type 2 diabetes mellitus. Egypt Rheumatol Rehabil 46, 321–326 (2019). https://doi.org/10.4103/err.err_37_19

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/err.err_37_19

Keywords