The role of disorders of the endothelial function in the development and progression of diabetic distal symmetric polyneuropathy depending on genetic factors


  • I.A. Zoriy Bukovinian State Medical University, Chernivtsi, Ukraine
  • N.V. Pashkovska Bukovinian State Medical University, Chernivtsi, Ukraine



type 2 diabetes mellitus, distal symmetric polyneuropathy, endothelial dysfunction, G894T polymorphism


Background. The purpose was to examine indicators of endothelial functional status in patients with diabetic distal symmetric polyneuropathy (DDSP) on the background of type 2 diabetes mellitus (DM), which depends on the polymorphism of the endothelial nitric oxide synthase gene (eNOS). Materials and methods. One-hundred and ten patients with DDSP on the background of type 2 DM were examined and composed the basic group. The average age of patients was 54.2 years (from 38 to 72 years). The patients were distributed according to DDSP severity: the first group consisted of 32 (29.1 %) patients with the initial manifestations of DDSP; the se­cond group included 58 (52.7 %) patients with moderate degree; the third group consisted of 20 (18.2 %) patients with severe DDSP. All patients underwent neurological examination using the scale of neuropathic symptomatic and neuropathic functional counting. The endothelial function was investigated by the content of stable metabolites of NO in the blood and the number of circulating endothelial cells in the blood. G894T polymorphism in eNOS gene was detected by polymerase chain reaction. Results. According to the data, most patients (78.5 %) presented with decreased amount of NO2-NO3.The number of desquamated endothelial cells was significantly increased in all examined patients compared to control. Comparing endothelial function parameters depending on G894T polymorphism in the eNOS gene, 43.6 % patients with a homozygous genotype for rare T allele were found to have a significant reduction of NO2-NO3content compared to control group (p < 0.05). Conclusions. There were significantly more pronounced disorders of the endothelial function in patients with moderate to severe DDSP on the background of type 2 DM. The results of the investigation showed the probable effect of G894T polymorphism of eNOS gene on the formation of a phenotype predisposing to the development of microangiopathies.


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Shakeel M. Recent advances in understanding the role of oxidative stress in diabetic neuropathy. Diabetes Metab Syndr. 2015;9(4):373-8. doi: 10.1016/j.dsx.2014.04.029.

Hosseini A, Abdollahi M. Diabetic neuropathy and oxidative stress: therapeutic perspectives. Oxid Med Cell Longev. 2013;2013:168039. doi: 10.1155/2013/168039.

Ziegler D. Current concepts in the management of diabetic polyneuropathy. Curr Diabetes Rev. 2011;7(3):208-20.

Krushinska ZG, Yuzvenko TYu, Pankiv VI. Frequency of cardiovascular complications in patients with type 2 diabetes mellitus depending on antihyperglycemic therapy. Mìžnarodnij endokrinologìčnij žurnal. 2018;14(6):570-578. doi: 10.22141/2224-0721.14.6.2018.146067. (in Ukrainian).

Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:8-14. doi: 10.1002/dmrr.2239.

Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005 Apr;28(4):956-62.

He Y, Fan Z, Zhang, et al. Polymorphisms of eNOS gene are associated with diabetic nephropathy: a meta-analysis. Mutagenesis. 2011 Mar;26(2):339-49. doi: 10.1093/mutage/geq100.

Vinik A, Ullal J, Parson HK, Casellini CM. Diabetic neuropathies: clinical manifestations and current treatment options. Nat Clin Pract Endocrinol Metab. 2006 May;2(5):269-81. doi: 10.1038/ncpendmet0142.

Min BW, Na JY, Juhng SW, et al. A polymorphism (T894G) in eNOS increases the risk of coronary atherosclerosis rather than intracranial atherosclerosis in Koreans. Acta Neurol Belg. 2010 Sep;110(3):255-62.

Forstermann U, Sessa W. Nitric oxide synthases: regulation and function. Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d. doi: 10.1093/eurheartj/ehr304.

Liatis S, Marinou K, Tentolouris N, Pagoni S, Katsilambros N. Usefulness of a new indicator test for the diagnosis of peripheral and autonomic neuropathy in patients with diabetes mellitus. Diabet Med. 2007 Dec;24(12):1375-80. doi: 10.1111/j.1464-5491.2007.02280.x.

Quattrini C, Tavakoli M, Jeziorska M, et al. Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes. 2007 Aug;56(8):2148-54. doi: 10.2337/db07-0285.

Bandeira SDM, da Fonseca LJS, Guedes GDS, Rabelo LA, Goulart MOF, Vasconcelos SML. Oxidative stress as an underlying contributor in the development of chronic complications in diabetes mellitus. Int J Mol Sci. 2013 Feb 5;14(2):3265-84. doi: 10.3390/ijms14023265.

Ziegler D, Papanas N, Vinik AI, Shaw JE. Epidemiology of polyneuropathy in diabetes and prediabetes. Handb Clin Neurol. 2014;126:3-22. doi: 10.1016/B978-0-444-53480-4.00001-1.

Soheilykhah S, Rashidi M, Dehghan F. Prevalence of peripheral neuropathy in diabetic patients. Iranian Journal of Diabetes and Obesity.2013;5(3):107-113.

Ibarra RCT, Rocha LJJ, Hernández OR, Nieves RRE, Leyva JR. Prevalence of peripheral neuropathy among primary care type 2 diabetic patients. Rev Med Chil. 2012 Sep;140(9):1126-31. doi: 10.4067/S0034-98872012000900004. (in Spanish).

Salvotelli L, Stoico V, Perrone F, et al. Prevalence of neuropathy in type 2 diabetic patients and its association with other diabetes complications: the Verona Diabetic Foot Screening Program. J Diabetes Complications. 2015 Nov-Dec;29(8):1066-70. doi: 10.1016/j.jdiacomp.2015.06.014.




How to Cite

Zoriy, I., & Pashkovska, N. (2021). The role of disorders of the endothelial function in the development and progression of diabetic distal symmetric polyneuropathy depending on genetic factors. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 15(2), 88–92.



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