Glutathione peroxidase and superoxide dismutase as markers of brain dysfunction in adolescents with diabetic ketoacidosis
https://doi.org/10.52420/2071-5943-2023-22-4-77-84
Abstract
Introduction. Diabetic ketoacidosis (DKA) is the most prevalent and severe acute complication of type 1 diabetes mellitus (DM) in children and adolescents. Oxidative stress (OS) is viewed on the one hand as a possible pathophysiological element in the development of this complication, and on the other, as an important factor that triggers the development of cerebral insufficiency in patients with type 1 DM.
Aim: to study the content of antioxidant enzymes in adolescents with type 1 DM in the setting of DKA and determine the correlation between the concentration of glutathione peroxidase (GP) and superoxide dismutase (SOD) and brain dysfunction after the manifestation of DKA.
Materials and methods. The study involved 52 adolescents (mean age − (16.7±1.25) years), of whom 26 were patients with type 1 DM complicated by DKA (study group; duration of disease − (6.5±0.46) years) and 26 were apparently healthy adolescents (control group). Cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA) test. Concentration of GP and SOD was assessed in serum samples by ELISA. Mann-Whitney test was used to assess differences between means, and Spearman’s coefficient was used to calculate correlations.
Results. Assessment using the MoCA tool showed a statistically significant cognitive decline in adolescents who had an episode of DKA (p = 0.0001). Another statistically significant finding in DKA was the lower mean levels of both GP (p = 0.0031) and SOD (p = 0.0173). Negative correlation was discovered between values obtained in the MoCA test and duration of disease and number of hospital admissions with DKA, and between GP levels and number of admissions with DKA, as reflected in patient history. Positive correlation was discovered between GP and SOD levels and values obtained in the MoCA test.
Discussion. Patients were found to have decreased antioxidant defense, along with brain dysfunction, after the manifestation of DKA. DKAassociated impairment of antioxidant defense is one of the pathophysiological mechanisms underpinning the development of cognitive dysfunction in adolescents with type 1 DM. Conclusion GP and SOD can be viewed as markers of DKA-associated brain dysfunction in patients with type 1 DM.
About the Author
Yu. B. Bykov
Stavropol State Medical University;
City Children’s Clinical Hospital named after G. K. Filippsky
Russian Federation
Russian Federation
Yuri V. Bykov, Ph.D. in medicine,
Stavropol
References
1. Dovi KS, Bajinka O, Conteh I. Evidence and possible mechanisms of probiotics in the management of type 1 diabetes mellitus. J Diabetes Metab Disord. 2022;21(1):1081−1094. https://doi.org/10.1007/s40200-022-01006-2.
2. Grabia M, Socha K, Soroczyńska J et al. Determinants related to oxidative stress parameters in pediatric patients with Type 1 diabetes mellitus. Nutrients. 2023;15(9):2084. https://doi.org/10.3390/nu15092084.
3. Qi X, Lu XT, Sun XH et al. The regulatory effect of total flavonoids of Sedum aizoon L. on oxidative stress in type 1 diabetic mice. Curr Res Food Sci. 2022;5:1140−1147. https://doi.org/10.1016/j.crfs.2022.06.010.
4. El Sayed NA, Aleppo G, Aroda VR et al. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 2022;46:S19−S40.
5. Otal Y, Kahraman FA, Haydar FG et al. Dynamic thiol/disulfide homeostasis as oxidative stress marker in diabetic ketoacidosis. Turk J Med Sci. 2021;51(2):743−748. https://doi.org/10.3906/sag-1904-55
6. Frontino G, Di Tonno R, Castorani V et al. Non-occlusive mesenteric ischemia in children with diabetic ketoacidosis: case report and review of literature. Front Endocrinol (Lausanne). 2022;13:900325. https://doi.org/10.3389/ fendo.2022.900325ж
7. Bykov YuV. Diabetic ketoacidosis in children and adolescents: from pathophysiology to prevention. Zabajkal’skij medicinskij vestnik = Zabaikalsky Medical Bulletin. 2021;2;85−95. (In Russ.).
8. Aldhaeefi M, Aldardeer NF, Alkhani N et al. Updates in the Management of Hyperglycemic Crisis. Front Clin Diabetes Healthc. 2022;2:820728. https://doi.org/10.3389/fcdhc.2021.820728.
9. Yaribeygi H, Sathyapalan T, Atkin SL et al. Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. Oxid Med Cell Longev. 2020;2020:8609213. https://doi.org/10.1155/2020/8609213.
10. Hoffman WH, Whelan SA, Lee N. Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes. PLoS One. 2021;16(7):e0254116. https://doi.org/10.1371/journal.pone.0254116.
11. Sies H. Oxidative stress: Concept and some practical aspects. Antioxidants (Basel). 2020;9:852. https://doi.org/10.3390/antiox9090852.
12. Olufunmilayo EO, Gerke-Duncan MB, Holsinger RMD. Oxidative Stress and Antioxidants in Neurodegenerative Disorders. Antioxidants (Basel). 2023;12(2):517. https://doi.org/10.3390/antiox12020517.
13. Bourgonje AR, Feelisch M, Faber KN et al. Oxidative stress and redox-modulating therapeutics in inflammatory bowel disease. Trends Mol Med. 2020;26:1034–1046. https://doi.org/10.1016/j.molmed.2020.06.00.
14. Ionescu-Tucker A, Cotman CW. Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiol Aging. 2021;107:86−95. https://doi.org/10.1016/j.neurobiolaging.2021.07.014.
15. Algorithms of specialized medical care for patients with diabetes mellitus. Edited by II Dedov, MV Shestakova, AYu Mayorov. Moscow. 2021;10. (In Russ.).
16. Vásquez KA, Valverde EM, Aguilar DV et al. Montreal Cognitive Assessment scale in patients with Parkinson Disease with normal scores in the Mini-Mental State Examination. Dement Neuropsychol. 2019;13(1):78-81. https://doi.org/10.1590/1980-57642018dn13-010008.
17. Li J, Shen X. Leptin concentration and oxidative stress in diabetic ketoacidosis. Eur J Clin Invest. 2018;48(10):e13006. https://doi.org/10.1111/eci.13006.
18. Murunga AN, Owira PMO. Diabetic ketoacidosis: an overlooked child killer in sub-Saharan Africa? Trop Med Int Health. 2013;18(11):1357–1364. https://doi.org/10.1111/tmi.12195.
19. Bykov YuV. Oxidative stress and diabetic encephalopathy: pathophysiological mechanisms. Sovremennye problemy nauki i obrazovaniya = Modern problems of science and education. 2022;6(2):39. (In Russ.).
20. Morella IM, Brambilla R, Morè L. Emerging roles of brain metabolism in cognitive impairment and neuropsychiatric disorders. Neurosci Biobehav Rev. 2022;142:104892. https://doi.org/10.1016/j.neubiorev.2022.104892.
21. Li H, Ren J, Li Y et al. Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes. Front Endocrinol (Lausanne). 2023;14:1134025. https://doi.org/10.3389/fendo.2023.1134025.
22. Yin F, Sancheti H, Patil I, Cadenas E. Energy metabolism and inflammation in brain aging and alzheimer’s disease. Free Radic Biol Med. 2016;100:108–122. https://doi.org/10.1016/j.freeradbiomed.2016.04.200.
23. Zhao Y, Wang H, Zhou J, Shao Q. Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer. Cancers (Basel). 2022;14(10):2560. https://doi.org/10.3390/cancers14102560.
24. Mohammedi K, Patente TA, Bellili-Muñoz N et al. Glutathione peroxidase-1 gene (GPX1) variants, oxidative stress and risk of kidney complications in people with type 1 diabetes. Metabolism. 2016;65(2):12−19. https://doi.org/10.1016/j.metabol.2015.10.004
25. Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress − A concise review. Saudi Pharm J. 2016;24(5):547– 553. https://doi.org/10.1016/j.jsps.2015.03.013.
26. Ghetti S, Kuppermann N, Rewers A et al. Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed Type 1 diabetes. Diabetes Care. 2020;43(11):2768−2775. https://doi.org/10.2337/dc20-0187.
27. Cameron FJ, Scratch SE, Nadebaum C et al. Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children. Diabetes Care. 2014;37(6):1554−1562. https://doi.org/10.2337/dc13-1904.
28. Varvarovská J, Racek J, Stozický F et al. Parameters of oxidative stress in children with Type 1 diabetes mellitus and their relatives. J Diabetes Complications. 2003;17(1):7−10. https://doi.org/10.1016/s1056-8727(01)00228-8.
29. Litvinenko LA, Chaika NA, Danilova LA. Features of the antioxidant status in children with diabetes mellitus. Medicina: teoriya i praktika = Medicine: Theory and Practice 2019;4(S):315–316. (In Russ.).
30. ЩеShcherbacheva LN, Lebedev NB, Knyazeva AP et al. Activity of antioxidant protection enzymes in insulin-dependent diabetes mellitus in children. Problemy endokrinologii = Problems of endocrinology. 1994;(5):7–9. (In Russ.).
31. Likidlilid A, Patchanans N, Poldee S, Peerapatdit T. Glutathione and glutathione peroxidase in type 1 diabetic patients. J Med Assoc Thai. 2007;90(9):1759−1767.
32. Faure P, Corticelli P, Richard MJ et al. Lipid peroxidation and trace element status in diabetic ketotic patients: influence of insulin therapy. Clin Chem. 1993;39(5):789−793.
Review
For citations:
Bykov YB. Glutathione peroxidase and superoxide dismutase as markers of brain dysfunction in adolescents with diabetic ketoacidosis. Ural Medical Journal. 2023;22(4):77-84. (In Russ.) https://doi.org/10.52420/2071-5943-2023-22-4-77-84
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