Clinical and laboratory markers of early diagnosis of diabetic polyneuropathy

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Abstract

Objective. To study the content of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor of type B kinase (TrkB) in patients at an early stage of diabetic polyneuropathy. Late diagnosis of diabetic polyneuropathy (DPN) is largely due to the presence of a subclinical stage, at which damage to the nervous system develops in the absence of complaints from the patient.

Materials and methods. 64 patients with type 2 diabetes mellitus and 11 persons of the control group were examined with an assessment of the pain status and the degree of peripheral neuropathy using PainDetect, TSS, NSS, NDS scales. Disturbance of nerve conduction along the nerves of the lower extremities was studied using electroneuromyography (ENMG). The study of the quantitative content of BDNF and TrkB in the serum was carried out with enzyme immunoassay.

Results. The increased serum concentrations of BDNF (p = 0.001) and TrkB (p = 0.007) were found with the development of clinically evident DPN as compared to patients without DPN. In patients with diabetes mellitus with subclinical DPN, there was established a statistically significant increase in serum BDNF expression (2.97 [2.44; 3.37] ng/ml in comparison with the values both in the control group (p = 0.022) and in diabetic patients without DPN (p = 0.017). The mean TrkB level in this group was 4.29 [3.48; 5.62] ng/ml, that is also higher than the corresponding values for patients without DPN (p = 0.032) and the control group (p = 0.025). The serum BDNF level correlates with the duration of diabetes mellitus (R = 0.524; p = 0.02), the intensity of neuropathic pain (R = 0.402; p = 0.001), the degree of axonal damage according to ENMG data (R = -0.242; p = 0.03). Correlations between the serum TrkB content and the severity of diabetes mellitus course (R = 0.482; p = 0.01), pain intensity (R = –0.383; p = 0.001), and impaired nerve conduction (R = –0.359; p = 0.003) were found.

Conclusions. The elevated expression and increased serum concentrations of BDNF and TrkB occur at the initial stage of the damage of peripheral nerve fibers and correlate with the degree of compensation for carbohydrate metabolism, the duration of diabetes and the severity of neural conduction disorders. The data obtained allow us to consider the increased serum levels of BDNF and TrkB as the markers of subclinical stage of diabetic polyneuropathy.

About the authors

Yu. V. Karakulova

E.A. Vagner Perm State Medical University

Author for correspondence.
Email: julia.karakulova@mail.ru
ORCID iD: 0000-0002-7536-2060
SPIN-code: 5066-6556

MD, PhD, Professor, Head of Department of Neurology and Medical Genetics

Russian Federation, Perm

D. Yu. Sosnin

E.A. Vagner Perm State Medical University

Email: julia.karakulova@mail.ru
ORCID iD: 0000-0002-1232-8826
SPIN-code: 4204-6796
Scopus Author ID: 36020670100

MD, PhD, Professor, Department of Faculty Therapy № 2, Occupational Pathology and Clinical Laboratory Diagnostics

Russian Federation, Perm

T. A. Filimonova

E.A. Vagner Perm State Medical University

Email: julia.karakulova@mail.ru

Candidate of Medical Sciences, Assistant, Department of Neurology and Medical Genetics

Russian Federation, Perm

I. V. Nekrasova

Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Acad-emy of Sciences

Email: julia.karakulova@mail.ru
ORCID iD: 0000-0002-6706-5912

Candidate of Biological Sciences, researcher, Laboratory of Immunoregulation, Institute of Ecology and Genetics of Microorganisms, Ural Branch of RAS

Russian Federation, Perm

References

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Supplementary files

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2. Figure. Serum content of the studied subgroups: a - BDNF, ng / ml: diagram of the range of the quantitative content of cerebral neurotrophin in the serum of the studied subgroups. Plots include the median (bitmap), upper and lower quartiles (25–75%), upper and lower bounds of the obtained values ​​(min – max). The X-axis indicates the ordinal numbers of the studied groups. The Y-axis is quantitative indicators of serum BDNF levels; b - TrkB, ng / ml: diagram of the range of the quantitative content of the cerebral neurotrophin receptor in the serum of the studied subgroups. Plots include the median (bitmap), upper and lower quartiles (25–75%), upper and lower bounds of the obtained values ​​(min – max). The X-axis indicates the ordinal numbers of the studied groups. The Y-axis is quantitative indicators of serum TrkB level.

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Copyright (c) 2021 Karakulova Y.V., Sosnin D.Y., Filimonova T.A., Nekrasova I.V.

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