The advantage of using complex therapy for diabetic polyneuropathy in patients with type 2 diabetes mellitus

• Alexander S. Ametov
• Anyuta A. Kosyan
• Evgeniya Yu. Pashkova
• Olga P. P'yanykh

Abstract

Aim. To assess the effect of complex therapy (combination of alpha-lipoic acid, cocarboxylase, cyanoco-balamin, triphosphadenine disodium trihydrate and nicotinamid) on the severity of diabetic neuropathy (DN) for patients with type 2 diabetes mellitus (T2DM).

Material and methods. 54 patients with T2DM and DN were divided into 2 groups by a random method. At the start of the study, the groups were comparable in terms of glycohemoglobin and duration of diabetes mellitus. The main group (1^st; n=33) for 10 days with a 6-month interval was prescribed complex therapy (alpha-lipoic acid, cocarboxylase, triphosphadenine, cyancobalamin, nicotinamide) and the comparison group (2^nd; n=21) was prescribed alpha-lipoic acid. In both groups, the state of the peripheral nervous system was assessed (TSS and NIS-LL scales were used, stimulating electroneuromyography), as well as levels of homocysteine (HC) and antioxidant system enzymes in the blood: superoxidеdismutase (SOD) and glutathioneperoxidase (GPO) before and after therapy.

Results and discussion. In the 1^st group, during therapy, a decreas e in the level of HC and a significant increase in the level of GPO were observed compared with the 2^nd group (p<0.05), the average scores on the TSS and NIS-LL scale in the 1^st group decreased more significantly than in the 2 ^nd group (p<0.05). In addition, at the end of therapy, according to electroneuromyography, in the 1^st group there was a significant positive dynamics of the electrophysiological parameters of the examined nerves (p<0.05), and in the 2^nd group no significant changeswere observed.

Conclusion. The course of complex therapy lasting 10 days with a 6-month interval, includingalpha-lipoic acid, cocarboxylase, triphosphadenine disodium trihydrate, cyancobalamin, nicotinamide, more effectively reduces the severity of DN in patients with T2DM.

Keywords:hyperhomocysteinemia, antioxidant enzymes, diabetic neuropathy, oxidative stress, type 2 diabetes mellitus, alpha-lipoic acid, cocarboxylase, cyanocobalamin

References

1. Global Report on Diabetes of WHO. 2016.

2. Tesfaye S., Boulton A.J., Dickenson A.H. Mechanisms and management of diabetic painful distal symmetrical polyneuropathy. Diabetes Care. 2013; 36: 2456-5.

3. Pop-Busui R., Boulton A.J.M., Feldman E.L., Bril V., et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017; 40 (1): 136-54.

4. Boulton A.J., Kirsner R.S., Vileikyte L. Clinical practice. Neuropathic diabetic foot ulcers. N Engl J Med. 2004; 351: 48-55.

5. Singh N., Armstrong D.G., Lipsky B.A. Preventing foot ulcers in patients with diabetes. JAMA. 2005; 293: 217-28.

6. Gore M., Brandenburg N.A., Dukes E., Hoffman D.L., et al. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005; 30: 374-85.

7. Ametov A.S., Chernikova N.A. Modern aspects of the treatment of diabetic polyneuropathy in patients with diabetes mellitus. Meditsinskiy sovet [Medical Council]. 2016; 8: 54-7. (in Russian)

8. Giacco F., Brownlee M., Schmidt A.M. Oxidative stress and diabetic complications. Circ Res. 2010; 107: 1058-70.

9. Baynes J.W., Thorpe S.R. Oxidative Stress in Diabetes. Antioxidants in Diabetes Management. In: L. Packer. New York: Marcel Dekker, 2000: 77-92.

10. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005; 54: 1615-25.

11. Ametov A.S., Kamynina L.L., Rozhdestvenskaya O.A., Pashko-va E.Yu. The positive metabolic and antioxidative properties of the testosterone replacement therapy at the combination of the type 2 diabetes mellitus and the hypogonadism. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2016; (3): 83-93. (in Russian)

12. Matsunami T., Sato Y., Sato T., Ariga S., et al. Oxidative stress and gene expression of antioxidant enzymes in the streptozotocin-induced diabetic rats under hyperbaric oxygen exposure. Int J Clin Exp Pathol. 2009; 3 (2): 177-88.

13. Kono Y., Fridovich I. Superoxide radical inhibits catalase. J Biol Chem. 1982; 257: 5751-4.

14. Sadi G., Eryilmaz N., TQtdncdoglu E., Cingir §., et al. Changes in expression profiles of antioxidant enzymes in diabetic rat kidneys. Diabetes Metab Res Rev. 2012; 28 (3): 228-35.

15. Strokov I.A., Bursa T.R., Drepa O., et al. Predisposing genetic factors for diabetic polyneuropathy in patients with type 1 diabetes: a population-based case-control study. Acta Diabetol. 2003; 40 (2): 375-9.

16. Srinivasan S., Stevens M., Wiley J.W. Diabetic peripheral neuropathy: evidence for apoptosis associated mitochondrial dysfunction. Diabetes. 2000; 11: 1932-8.

17. Creager M.A., Luscher T.F., Cosentino F., Beckman J.A. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Circulation. 2003; 108: 1527-32.

18. Cao Y., Chai J.G., Chen Y.C., Zhao J., et al. Beneficial effects of danshensu, an active component of salvia miltiorrhiza, on homocysteine metabolism via the trans-sulphuration pathway in rats. Br J Pharmacol 2009; 157: 482-90.

19. Weiss N., Zhang Y.Y., Heydrick S., Bierl C., et al. Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. Proc Natl Acad Sci USA. 2001; 98 (22): 12 503-8.

20. Jacobsen D.W. Hyperhomocysteinemia and oxidative stress. Arte-rioscler Thromb Vasc Biol. 2000; 20: 1182-4.

21. Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006; 580 (13): 2994-3005.

22. Ametov A.S., Kosyan A.A. The role of homocysteine in the development of diabetic polyneuropathy and endothelial dysfunction. Endokri-nologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2019; 8 (1): 32-9. (in Russian)

23. Wang H., Cui K., Xu K., Xu S. Association between plasma homocysteine and progression of early nephropathy in type 2 diabetic patients. Int J Clin Exp Med. 2015; 8 (7): 11 174-80.

24. Li J., Shi M., Zhang H., Yan L., et al. Relation of homocysteine to early nephropathy in patients with Type 2 diabetes. Clin Nephrol. 2012; 77 (4): 305-10.

25. Brazionis L., Rowley K., Itsiopoulos C., Harper C.A., et al. Homocysteine and diabetic retinopathy. Diabetes Care. 2008; 31 (1): 50-6.

26. Rudy A., Kowalska I., Strqczkowski M., Kinalska I. Homocysteine concentrations and vascular complications in patients with type 2 diabetes. Diabetes Metab. 2005; 31 (2): 112-7.

27. Hoogeveen E.K., Kostense P.J., Jakobs C., et al. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation. 2000; 101: 1506-11.

28. The DCCT Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995: 122: 561-8.

29. Ametov A.S., Strokov I.A., Barinov A.N. Alpha-lipoic acid in the treatment of symptomatic diabetic polyneuropathy: a symptomatic diabetic neuropathy (SYDNEY) trial. Farmateka [Pharmateca]. 2004; 11 (88): 69-73. (in Russian)

30. Ziegler D., Nowak H., Kempler P., et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alphalipoic acid: a meta-analysis. Diabet Med. 2004; 21 (2): 114-21.

31. Gurieva I.V., Marchenkova E.S. Combined pain therapy in patients with diabetic polyneuropathy. Russkiy meditsinskiy zhurnal [Russian Medical Journal]. 2015; (27): 1649-52. (in Russian)

32. Haupt E., Ledermann H., KopckeW. Benfotiamine in the treatment of diabetic polyneuropathy - a three-week randomized controlled pilot-study (BEDIP study). Int J Clin Pharmacol Ther. 2005; 43 (2): 71-7.

33. Stracke H., Gaus W., Achenbach U., Federlin K., et al. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008; 116 (10): 600-5.

34. Stracke H., Lindemann A., Federlin K. A benfotiamine - vitamin B combination in the treatment of diabetic polyneuropathy . Exp Clin Endocrinol Diabetes. 1996; 104: 311-6.

35. Jacobs A.M, Cheng D. Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5’-phosphate. Rev Neurol Dis. 2011; 8: 39-47.

36. Ametov A.S., Kosyan A.A., Pashkova E.Yu. The effect of hyperhomocysteinemia on the level of the antioxidant enzymes in the blood and on the severity of diabetic neuropathy for patients with type 2 diabetes mellitus. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2019; 8 (2): 9-15. (in Russian)

37. Wile D.J., Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care. 2010; 33 (1): 156-61.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)