THE RELATIONSHIP BETWEEN CARDIOVASCULAR AUTONOMIC NEUROPATHY AND BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) GENE EXPRESSION IN PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS
DOI:
https://doi.org/10.21856/j-PEP.2024.2.05Keywords:
diabetes mellitus, brain derived neurotrophic factor, cardiac autonomic neuropathy, diabetic polyneuropathy, cardiac autonomic reflex testsAbstract
Cardiovascular autonomic neuropathy (CAN) is a serious risk factor for cardiovascular morbidity and mortality in patients with diabetes mellitus (DM) and prediabetes. On the other hand, gene brain-derived neurotrophic factor (BDNF) promotes synthesis of nerve growth factors. Degeneration of autonomic nerves is a common feature of autonomic neuropathy.
The aim of the study was to determine the frequency of cardiac autonomic neuropathy detection and the relationship between the presence of this complication and the level of BDNF gene expression in patients with newly diagnosed type 2 diabetes.
Materials and methods. We examined 52 patients with newly diagnosed type 2 DM, 16 males and 36 females (aged 60,9±1,55 years, BMI – 32,98±0,73 kg/m2, systolic blood pressure – 148,27±3,3 mmHg, diastolic blood pressure – 90,08±2,14 mmHg, HbA1c – 7,77±0,18%, fasting glucose – 8,72±0,36 mmol/L, GFR – 78,98±2,19 ml/min/1.73m2) (data are presented everywhere as mean±SEM). All patients were performed five cardiovascular autonomic reflex tests (CARTs) by Ewing with assessment of heart rate variability, diagnostic diabetic polyneuropathy by Toronto scale and real-time PCR analysis for quantitative evaluation of BDNF gene. The diagnosis of CAN was confirmed in patients with 2 positive tests. The statistical analysis was performed using SPSS statistical package version 23.0 for Windows.
Results. CAN with 2 pathological tests was diagnosed in 50% patients, 3 pathological tests –34,6%. Mild diabetic polyneuropathy was detected in 28,8% patients, moderate – 19,2%, severe – 19,2%. We found negative correlation between levels of BDNF gene expression and the total score of CARTs, В (95% CІ) -28,5 (-55,79/-1,21), р=0,01), and negative correlation between levels of BDNF gene expression and the total score of Toronto scale, В (95% CI) -0,007 (-0,013/-0,002), р=0,011.
Conclusion. We investigated the relationship between the level of BDNF gene expression and the total score of the five cardiovascular autonomic reflex tests by D. Ewing as the "gold standard" for the detection of cardiac autonomic neuropathy, which indicates the probable role of the influence of the BDNF gene on the development and progression of cardiac autonomic neuropathy in patients with newly diagnosed type 2 diabetes.
References
International Diabetes Federation. Diabetes Atlas. 9th ed. 2021, available at: https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.
International Diabetes Federation. Diabetes Atlas. 8th ed. 2019, available at: https://diabetesatlas.org/key-messages.html.
Selvarajah D, et al. Lancet Diabetes Endocrinol 2019; 7(12): 938-948. http://doi.org/10.1016/S2213-8587(19)30081-6.
Feldman E, et al. Nat Rew Dis Primers 2019;5(1): 42. http://doi.org/10.1038/s41572-019-0097-9.
Pafili K, Papanas N, Ziegler D. Angiology 2018;69(9): 752-754. http://doi.org/10.1177/0003319717751759.
Man'kovs'kyj B.N. Diabetychna polinejropatija: vid golovy do kinchykiv pal'civ. 2021, available at: http://lib.inmeds.com.ua:8080/jspui/handle/lib/3758
Motatajana A, Maier S, Baiko Z, et al. BMC Neurol 2018;18(1): 126. http://doi.org/10.1186/s12883-018-1125-1.
Oros MM, Savyc'ka NO. Zdorov’ja Ukrai'ny 2018;15-16: 436-437.
Zakin E, Abrams R, Simpson D. Semin Neurol 2019;39(5): 560-569. http://doi.org/10.1055/s-0039-1688978.
Sergijenko VO. Zhurn NAMN Ukrai'ny 2015;21(2): 142-157.
Agashe S, Petak S. Methodist Debakey Cardiovascular J 2018;14(4): 251-256. http://doi.org/10.14797/mdcj-14-4-251.
Pop-Busui R, Boulton A, Feldman E, et al. Diabetes Care 2017;40(1): 136-154. http://doi.org/10.2337/dc16-2042.
Andersen ST, Witte DR, Fleischer J, et al. Diabetes Care 2018;4(12): 2586- 2594. http://doi.org/10.2337/dc18-1411.
Stepura OA, Shekera OG, Man'kovs'kyj BM. Probl Endokryn Patologii' 2019;2: 60-65. https://doi.org/10.21856/j-PEP.2019.2.09
Dimova R, Tankova T, Groseva D, et al. J Diabetes Compl 2017;31(3): 537-543. http://doi.org/10.1016/j.jdiacomp.2016.11.002.
Ziegler D, Voss A, Rathmann W, et al. Diabetologia 2015;58: 1118-1128. http://doi.org/10.1007/s00125-015-3534-7.
Bax G, Bellavere F. Acta Diabetol 2019;56(5): 603. http://doi.org/10.1007/s00592-018-01281-7.
Breder IS, Sposito AC. Rev Assoc Med Bras 2019;65(1): 56-60. http://doi.org/10.1590/1806-9282.65.1.56.
Azoulay D, Abed S, Sfadi A, et al. Acta Diabetol 2020;57(7): 891-898. http://doi.org/10.1007/s00592-020-01508-6.
Fudalei E, et al. Ophtalmic Res 2021;64(3) : 345-355. http://doi.org/10.1159/000514441.
Mankovsky B, Zherdova N, Dalhuisen I, et al. Diabetic Med 2018;35(12): 1663-1670. http://doi.org/10.1111/dme.13800.
Zherdova NM, Stepura OA, Drevyc'ka TI, Kostic'ka IM. Probl Endokryn Patologii' 2023;2: 14-21. https://doi.org/10.21856/j-PEP.2023.2.02.
Circulation 1996;93(5): 1043-1065, available at: https://pubmed.ncbi.nlm.nih.gov/8598068/
Kakavand Hamidi A, Radfar M, Amoli MM. Pharmacol Rep 2018;70: 1-5. http://doi.org/10.1016/j.pharep.2017.04.017.
Yehya A, Altaany Z, Beni-Yonis O. Eur Rev Med Pharmocol Sci 2023;27(14): 6682-6690. http://doi.org/10.26355/eurrev_202307_33138.
Zhen YF, Liu XY, Li YK, et al. Psychosom Med 2019;81(6) : 488-494. http://doi.org/10.1097/PSY.0000000000000709.
Hu L, Qi S, Zhang K, Fu Q. Andrologia 2018;50(3). http://doi.org/10.1111/and.12924.
ISSN 
ISSN 
