Correlation between vitamin D deficiency, VDR receptor levels and apoptosis markers in comorbid patients with type 2 diabetes mellitus and arterial hypertension
Abstract. Vitamin D plays a significant role in the organism, participating in regulation of the immune response, inflammation, apoptosis and cell proliferation. Particularly important is the effect of vitamin D at the course of type 2 diabetes mellitus (T2DM), when chronic inflammation and pancreatic β-cells dysfunction are taking place. Hypovitaminosis D can also worsen the course of arterial hypertension (AH) and contribute to the development of cardiovascular diseases, the leading cause of death in many countries. Vitamin D deficiency and genetic features of its receptor (VDR) can worsen the course of these diseases.Dugusheva V.A., Kotova Yu.A., Shevtsova V.I., Shchegoleva V.E.
The aim: to evaluate the correlation between vitamin D deficiency, VDR levels, and apoptosis markers in patients with T2DM and AH.
Material and methods. The study involved 160 individuals (130 with T2DM and AH and 30 healthy persons). Patients with T2DM and AH were divided into 4 groups depending on the vitamin D level. Levels of vitamin D, glucose, netrin-1, heat shock protein 70 (HSP-70), and VDR were analyzed.
Results. The study revealed changes in netrin-1 and HSP-70 levels in comorbid patients with T2DM and AH having vitamin D deficiency, which confirms its association with impaired regulation of apoptosis and oxidative stress. A decrease in HSP-70 can contribute to the progression of atherosclerosis, and changes in netrin-1 are associated with inflammatory processes and complications of T2DM and AH. Insulin resistance disrupts the circulation of netrin-1, which contributes to chronic inflammation and insulin resistance. In patients with optimal vitamin D levels in the present study, VDR was significantly higher comparatively to other groups. After correction of vitamin D deficiency, normalization of inflammation and apoptosis biomarkers was observed.
Conclusion. Achieving target levels of vitamin D can improve clinical outcomes in case of T2DM and AH, which requires further research.
Keywords
vitamin D
VDR
type 2 diabetes mellitus
arterial hypertension
netrin-1
heat shock protein 70
References
1. Булгакова С.В., Башинская С.А., Захарова Н.О., Тренева Е.В., Николаева А.В. Витамин D: роль в развитии ожирения, инсулинорезистентности, сахарного диабета типа 2 у лиц пожилого и старческого возраста. Клиническая геронтология. 2021;27(9–10):16–22. (Bulgakova SV, Bashinskaya SA, Zakharova NO, Treneva EV, Nikolaeva AV. Vitamin D: Role in the development of obesity, insulin resistance, type 2 diabetes mellitus in the elderly. Klinicheskaya gerontologiya = Clinical Gerontology. 2021;27(9–10):16–22 (In Russ.)).
EDN: WKSAWE. https://doi.org/10.26347/1607-2499202109-10016-022
2. Громова О.А., Торшин И.Ю. Витамин D – смена парадигмы. Под ред. акад. РАН Е.И. Гусева, проф. И.Н. Захаровой. М.: ГЕОТАР-Медиа. 2018; 576 c. (Gromova OA, Torshin IYu. Vitamin D – a paradigm shift. Edited by academician of RAS E.I. Guseva, professor I.N. Zakharova. Moscow: GEOTAR-Media. 2018; 576 pp. (In Russ.)). ISBN: 978-5-9704-4730-7.
3. Gulseth HL, Wium C, Angel K, Eriksen EF, Birkeland KI. Effects of vitamin D supplementation on insulin sensitivity and insulin secretion in subjects with type 2 diabetes and vitamin D deficiency: A randomized controlled trial. Diabetes Care. 2017;40(7):872–78.
PMID: 28468770. https://doi.org/10.2337/dc16-2302
4. Giri D, Pintus D, Burnside G, Ghatak A, Mehta F, Paul P, Senniappan S. Treating vitamin D deficiency in children with type I diabetes could improve their glycaemic control. BMC Res Notes. 2017;10(1):465.
PMID: 28882195. PMCID: PMC5590233. https://doi.org/10.1186/s13104-017-2794-3
5. Komisarenko YI, Bobryk MI. Vitamin D deficiency and immune disorders in combined endocrine pathology. Front Endocrinol (Lausanne). 2018;9:600.
PMID: 30356853. PMCID: PMC6190873. https://doi.org/10.3389/fendo.2018.00600
6. Степанова А.П., Каронова Т.Л., Быстрова А.А., Бреговский В.Б. Роль дефицита витамина D в развитии сахарного диабета 2 типа и диабетической нейропатии. Сахарный диабет. 2018;21(4):301–306. (Stepanova AP, Karonova TL, Bystrova AA, Bregovsky VB. Role of vitamin D deficiency in type 2 diabetes mellitus and diabetic neuropathy development. Sakharnyy diabet = Diabetes Mellitus. 2018;21(4):301–306 (In Russ.)).
EDN: YKXEFF. https://doi.org/10.14341/DM9583
7. Arneth B, Arneth R, Shams M. Metabolomics of type 1 and type 2 diabetes. Int J Mol Sci. 2019;20(10):2467.
PMID: 31109071. PMCID: PMC6566263. https://doi.org/10.3390/ijms20102467
8. Renke G, Starling-Soares B, Baesso T, Petronio R, Aguiar D, Paes R. Effects of vitamin D on cardiovascular risk and oxidative stress. Nutrients. 2023;15(3):769.
PMID: 36771474. PMCID: PMC9920542. https://doi.org/10.3390/nu15030769
9. Khanijou V, Zafari N, Coughlan MT, MacIsaac RJ, Ekinci EI. Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease. Diabetes Metab Res Rev. 2022;38(6):e3556.
PMID: 35708187. PMCID: PMC9541229. https://doi.org/10.1002/dmrr.3556
10. Дугушева В.А., Котова Ю.А., Антакова Л.Н. Взаимосвязь риска развития сахарного диабета 2 типа и гиповитаминоза D (обзор литературы). Вестник новых медицинских технологий. Электронное издание. 2024;18(5):22–27. (Dugusheva VA, Kotova YuA, Antakova LN. The relationship between the risk of type 2 diabetes mellitus and hypovitaminosis D (literature review). Vestnik novykh meditsinskikh tekhnologiy. Elektronnoe izdanie = Journal of New Medical Technologies. eEdition. 2024;18(5):22–27 (In Russ.)).
EDN: EPQQIR. https://doi.org/10.24412/2075-4094-2024-5-1-3
11. Некрасова Е.В., Машкина В.В., Орлов С.В. Нетрин-1 и окисленные липопротеины низкой плотности независимо увеличивают уровень мембранного белка APOA1 в первичной культуре макрофагов человека. Актуальные проблемы биомедицины – 2024. Материалы XXX Всероссийской конференции молодых ученых с международным участием. 2024:151. (Nekrasova EV, Mashkina VV, Orlov SV. Netrin-1 and oxidized low-density lipoproteins independently increase the level of the membrane protein APOA1 in the primary culture of human macrophages. Actual problems of biomedicine – 2024. Proceedings of the XXX All-Russian Conference of Young Scientists with International Participation. 2024:151 (In Russ.)). EDN: VDJIOC.
12. Калинченко С.Ю., Самбурская О.В., Ворслов Л.О., Свидерская Т.А., Смыкалова А.С. Сахарный диабет 2-го типа и витамин D: механизмы воздействия на углеводный обмен. Вопросы диетологии. 2022;12(3):45–52. (Kalinchenko SYu, Samburskaya OV, Vorslov LO, Sviderskaya TA, Smykalova AS. Type 2 diabetes and vitamin D: Mechanism of action on carbohydrate metabolism. Voprosy dietologii = Nutrition. 2022;12(3):45–52 (In Russ.)).
EDN: NPINQW. https://doi.org/10.20953/2224-5448-2022-3-45-52
13. Пигарова Е.А., Рожинская Л.Я., Белая Ж.Е., Дзеранова Л.К., Каронова Т.Л., Ильин А.В. с соавт. Клинические рекомендации Российской ассоциации эндокринологов по диагностике, лечению и профилактике дефицита витамина D у взрослых. Проблемы эндокринологии. 2016;62(4):60–84. (Pigarova EA, Rozhinskaya LYa, Belaya ZhE, Dzeranova LK, Karonova TL, Ilyin AV et al. Russian association of endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults. Problemy endokrinologii = Problems of Endocrinology. 2016;62(4):60–84 (In Russ.)).
EDN: WMZICF. https://doi.org/10.14341/probl201662460-84
14. Котова Ю.А., Зуйкова А.А., Пашков А.Н. Диагностическое значение шаперонной активности белков теплового шока 70 при коронарном атеросклероз. CardioСоматика. 2019;10(3):60–64. (Kotova YuA, Zuikova AA, Pashkov AN. Diagnostic value of chaperone activity of heat shock proteins 70 in coronary atherosclerosis. CardioSomatika = CardioSomatics. 2019;10(3):60–64 (In Russ.)).
EDN: HSXEDC. https://doi.org/10.26442/22217185.2019.3.190400
15. Liu C, Ke X, Wang Y, Feng X, Li Q, Zhang Y et al. The level of netrin-1 is decreased in newly diagnosed type 2 diabetes mellitus patients. BMC Endocr Disord. 2016;16(1):33.
PMID: 27255377. PMCID: PMC4890509. https://doi.org/10.1186/s12902-016-0112-z
16. Ramkhelawon B, Hennessy EJ, Ménager M, Ray TD, Sheedy FJ, Hutchison S et al. Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med. 2014;20(4):377–84.
PMID: 24584118. PMCID: PMC3981930. https://doi.org/10.1038/nm.3467
About the Authors
Valeria A. Dugusheva, MD, assistant at the Department of clinical laboratory diagnostics, N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia. Address: 394036, Voronezh, 10 Studencheskaya St.E-mail: semikolenovaval@yandex.ru
ORCID: https://orcid.org/0000-0002-7342-2218. eLibrary SPIN: 7689-6456
Yulia A. Kotova, MD, Dr. Sci. (Medicine), associate professor, head of the Department of clinical laboratory diagnostics, N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia. Address: 394036, Voronezh, 10 Studencheskaya St.
E-mail: kotova_u@inbox.ru
ORCID: https://orcid.org/0000-0003-0236-2411. Scopus ID: 57222073532. eLibrary SPIN: 8518-0355
Veronika I. Shevtsova, MD, associate professor of the Department of infectious diseases and clinical immunology, N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia. Address: 394036, Voronezh, 10 Studencheskaya St.
E-mail: shevvi@yandex.ru
ORCID: https://orcid.org/0000-0002-1707-436X. Scopus ID: 57222071746. eLibrary SPIN: 1393-7808
Victoria E. Shchegoleva, 3rd year student of the Faculty of general medicine, N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia. Address: 394036, Voronezh, 10 Studencheskaya St.
E-mail: vikaut0vaz@list.ru
ORCID: https://orcid.org/0009-0008-3336-5758. eLibrary SPIN: 2078-9210
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