Type 2 diabetes mellitus in patients with acute ischemiс stroke is associated with a decrease in plasma glutathione levels
https://doi.org/10.30629/2658-7947-2020-25-5-29-35
Abstract
Ischemic stroke (IS) and type 2 diabetes mellitus are factors that affect the homeostasis of low-molecularweight aminothiols (cysteine, homocysteine, glutathione etc.). It has already been shown that IS in the acute period led to a decrease a level of reduced forms of aminothiols, but it is not clear whether type 2 diabetes mellitus has a noticeable effect there.
Objective: to reveal the features of homeostasis of aminothiols in patients with type 2 diabetes mellitus in acute IS.
Material and methods. The study involved 76 patients with primary middle cerebral artery IS in the first 10–24 hours after development of neurological symptoms. Group 1 included 15 patients with IS and type 2 diabetes mellitus, group 2 — 61 patients with IS and stress hyperglycemia. Their total plasma levels of cysteine, homocysteine, and glutathione, their reduced forms, and redox status were determined at admission (in the first 24 hours after IS).
Results. There was a decrease in the level of total glutathione level (1.27 vs. 1.65 μM, p = 0.021), as well as its reduced form (0.03 vs. 0.04 μM, p = 0.007) in patients with IS and type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who had a low redox status of homocysteine (0.65–1.2%) and glutathione (0.7–2.0%) were also characterized by a decrease in total glutathione level (p = 0.02; p = 0.03).
Conclusion. Thus, type 2 diabetes mellitus is associated with a decrease in the level of total glutathione in acute IS. Probably, type 2 diabetes mellitus is characterized by a particular relationship between the metabolism of homocysteine, glutathione and glucose. Therefore, the search for homocysteine-dependent approaches to correct glutathione metabolism in type 2 diabetes mellitus may be of interest as an adjuvant therapy for IS.
About the Authors
M. Yu. MaksimovaRussian Federation
Moscow
A. V. Ivanov
Russian Federation
Department of Molecular and Cell Pathophysiology
Moscow
K. A. Nikiforova
Russian Federation
Department of Molecular and Cell Pathophysiology
Moscow
F. R. Ochtova
Russian Federation
Department of Nervous Diseases
Moscow
E. T. Suanova
Russian Federation
Department of Nervous Diseases
Moscow
E. D. Virus
Russian Federation
Department of Molecular and Cell Pathophysiology
Moscow
I. S. Zimina
Russian Federation
Department of Molecular and Cell Pathophysiology
Moscow
M. A. Piradov
Russian Federation
Moscow
A. A. Kubatiev
Russian Federation
Department of Molecular and Cell Pathophysiology
Moscow
References
1. Chen R., Ovbiagele B., Feng W. Diabetes and Stroke: Epidemiology, Pathophysiology, Pharmaceuticals and Outcomes. Am. J. Med. Sci. 2016;351(4):380–386. https://doi.org/10.1016/j.amjms.2016.01.011
2. Ivanov A.V., Alexandrin V.V., Paltsyn A.A., Nikiforova K.A., Virus E.D., Luzyanin B.P. et al. Plasma low-molecular-weight thiol/disulphide homeostasis as an early indicator of global and focal cerebral ischaemia. Redox Rep. 2017;22:460–466. DOI: 10.1080/13510002.2017.1311464
3. Maksimova M.Y., Ivanov A.V., Virus E.D., Alexandrin V.V., Nikiforova K.A., Bulgakova P.O. et al. Disturbance of thiol/disulfide aminothiols homeostasis in patients with acute ischemic stroke stroke: Preliminary findings. Clin. Neurol. Neurosurg. 2019;183:105393. https://doi.org/10.1016/j.clineuro.2019.105393
4. Duman B.S., Oztürk M., Yilmazeri S., Hatemi H. Thiols, malonaldehyde and total antioxidant status in the Turkish patients with type 2 diabetes mellitus. Tohoku J. Exp. Med. 2003;201:147–155. https://doi.org/10.1620/tjem.201.147
5. Tessier D., Khalil A., Fülöp T. Effects of an oral glucose challenge on free radicals/antioxidants balance in an older population with type 2 diabetes. J. Gerontol. A Biol. Sci. Med. Sci. 1999;54:541–545. https://doi.org/10.1093/gerona/54.11.m541
6. Karolczak K., Kubalczyk P., Głowacki R., Pietruszyński R, Watała C. An inverse relationship between plasma glutathione concentration and fasting glycemia in patients with coronary artery disease and concomitant type 2 diabetes: A pilot study. Adv. Clin. Exp. Med. 2017;26:1359–1366. https://doi.org/10.17219/acem/65441
7. Lutchmansingh F.K., Hsu J.W., Bennett F.I., Badaloo A.V., McFarlane-Anderson N., Gordon-Strachan G.M. et al. Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia. PLoS One. 2018;13:e0198626. https://doi.org/10.1371/journal.pone.0198626
8. Brott T., Adams H.P.Jr., Olinger C.P., Marler J.R., Barsan W.G., Biller J. et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864–870. https://doi.org/10.1161/01.str.20.7.864
9. Sulter G., Steen C., De Keyser J. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke. 1999;30:1538–1541. https://doi.org/10.1161/01.str.30.8.1538
10. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2019;42(1):S1–193.
11. Cerielo A., Motz E., Cavarape A., Lizzio S., Russo A., Quatraro A. et al. Hyperglycemia counterbalances the antihypertensive effect of glutathione in diabetic patients: evidence linking hypertension and glycemia through the oxidative stress in diabetes mellitus. J. Diabetes Complications. 1997;11:250–255. https://doi.org/10.1016/s1056-8727(97)00021-4
12. Etemad A., Vasudevan R., Aziz A.F., Yusof A.K., Khazaei S., Fawzi N. et al. Analysis of selected glutathione S-transferase gene polymorphisms in Malaysian type 2 diabetes mellitus patients with and without cardiovascular disease. Genet. Mol. Res. 2016;15. https://doi.org/10.4238/gmr.15025845
13. Lu S.C. Glutathione synthesis. Biochim. Biophys. Acta. 2013;1830(5):3143–3153. https://doi.org/10.1016/j.bbagen.2012.09.008
14. Guo J.M., Liu A.J., Zang P., Dong W.Z., Ying L., Wang W. et al. ALDH2 protects against stroke by clearing 4-HNE. Cell. Res. 2013;23(7):915–30. https://doi.org/10.1038/cr.2013.69
15. Jotic A., Covickovic S.N., Kostic V.S., Lalic K., Milicic T., Mijajlovic M. et al. Type 2 diabetic patients with ischemic stroke: decreased insulin sensitivity and decreases in antioxidant enzyme activity are related to different stroke subtypes, Int. J. Endocrinol. 2013;2013:401609. https://doi.org/10.1155/2013/401609
16. Venkat P., Chopp M., Chen J. Blood-Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke. J. Am. Heart. Assoc. 2017;6(6):e005819. https://doi.org/10.1161/JAHA.117.005819
17. Poulsen R.C., Knowles H.J., Carr A.J., Hulley P.A. Cell differentiation versus cell death: extracellular glucose is a key determinant of cell fate following oxidative stress exposure. Cell Death Dis. 2014;5:e1074. https://doi.org/10.1038/cddis.2014.52
18. Bruno A., Kent T.A., Coull B.M., Shankar R.R., Saha C., Becker K.J. et al. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008;39(2):384–389. https://doi.org/10.1161/STROKEAHA.107.493544
19. Avgerinos K., Tziomalos K. Effects of glucose-lowering agents on ischemic stroke. World J. Diabetes. 2017;8:270–277. https://doi.org/10.4239/wjd.v8.i6.270
20. Robbins M.A., Elias M.F., Budge M.M., Brennan S.L., Elias P.K. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study. Clin. Chem. Lab. Med. 2005;43:1101–1106. https://doi.org/10.1515/CCLM.2005.192
21. Das S., Reynolds T., Patnaik A., Rais N., Fink L.M., Fonseca V.A. Plasma homocysteine concentrations in type 2 diabetic patients in India: relationship to body weight. J. Diabetes Complications. 1999;13:200–203. https://doi.org/10.1016/s10568727(99)00045-8
22. Gunawardena H.P., Silva R., Sivakanesan R., Ranasinghe P., Katulanda P. Poor Glycaemic Control Is Associated with Increased Lipid Peroxidation and Glutathione Peroxidase Activity in Type 2 Diabetes Patients. Oxid. Med. Cell. Longev. 2019;9471697. https://doi.org/10.1155/2019/9471697
23. Li G., Liu Y., Li X., Ning Z., Sun Z., Zhang M. et al. Association of PAI-1 4G/5G Polymorphism with Ischemic Stroke in Chinese Patients with Type 2 Diabetes Mellitus. Genet. Test Mol. Biomarkers. 2018;22:554–560. https://doi.org/10.1089/gtmb.2018.0130
24. Nguyen D., Hsu J.W., Jahoor F., Sekhar R.V. Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIVinfected patients. J. Clin. Endocrinol. Metab. 2014;99:169–177. https://doi.org/10.1210/jc.2013-2376
Review
For citations:
Maksimova M.Yu., Ivanov A.V., Nikiforova K.A., Ochtova F.R., Suanova E.T., Virus E.D., Zimina I.S., Piradov M.A., Kubatiev A.A. Type 2 diabetes mellitus in patients with acute ischemiс stroke is associated with a decrease in plasma glutathione levels. Russian neurological journal. 2020;25(5):29-35. (In Russ.) https://doi.org/10.30629/2658-7947-2020-25-5-29-35