The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Mkrtumyan A.M.

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Bulgakova S.V.

Samara State Medical University

Sharonova L.A.

Samara State Medical University, Health Ministry of Russia, Samara, Russia

Dolgikh Ya.A.

Samara State Medical University

Merzlova P.Ya.

Samara State Medical University

Kosareva O.V.

Samara State Medical University, Health Ministry of Russia, Samara, Russia

Arguments and facts

Authors:

Mkrtumyan A.M., Bulgakova S.V., Sharonova L.A., Dolgikh Ya.A., Merzlova P.Ya., Kosareva O.V.

More about the authors

Journal: Non Nocere. New Therapeutic Journal. 2025;(5‑6): 98‑107

Read: 158 times

To cite this article:

Mkrtumyan AM, Bulgakova SV, Sharonova LA, Dolgikh YaA, Merzlova PYa, Kosareva OV. Arguments and facts. Non Nocere. New Therapeutic Journal. 2025;(5‑6):98‑107. (In Russ.)

References:

  1. Muromtseva G.A., Kontsevaya A.V., Konstantinov V.V., et al. The Prevalence of Non-Infectious Diseases Risk Factors in Russian Population in 2012-2013 Years. The Results of ECVD-RF. Cardiovascular Therapy and Prevention. 2014;13(6):4-11. (In Russ.) https://doi.org/10.15829/1728-8800-2014-6-4-11
  2. Mkrtumyan AM. Obesity: a contemporary world issue. An overview of possible therapeutic approaches to therapy. Meditsinskiy sovet = Medical Council. 2018;(4):81-85. (In Russ.) https://doi.org/10.21518/2079-701X-2018-4-81-85
  3. Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C. Obesity as a Disease. Med Clin North Am. 2018 Jan;102(1):13-33.  https://doi.org/10.1016/j.mcna.2017.08.004
  4. Shestakova E.A., Lunina E.Y., Galstyan G.R., Shestakova M.V., Dedov I.I. Type 2 diabetes and prediabetes prevalence in patients with different risk factor combinations in the NATION study. Diabetes mellitus. 2020;23(1):4-11. (In Russ.) https://doi.org/10.14341/DM12286
  5. Schnurr TM, Jakupović H, Carrasquilla GD, et al. Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: a case-cohort study. Diabetologia. 2020 Jul;63(7):1324-1332. https://doi.org/10.1007/s00125-020-05140-5
  6. Magliano DJ, Boyko EJ; IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS [Internet]. 10th ed. Brussels: International Di-abetes Federation; 2021. PMID: 35914061 
  7. GBD2021 Forecasting Collaborators. Burden of disease scenarios for 204 countries and territories, 2022-2050: a forecasting analysis for the Global Bur-den of Disease Study 2021. Lancet. 2024 May 18;403(10440):2204-2256. https://doi.org/10.1016/S0140-6736(24)00685-8
  8. Richter B, Hemmingsen B, Metzendorf MI, Takwoingi Y. Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia. Cochrane Database Syst Rev. 2018 Oct 29;10(10): CD012661. https://doi.org/10.1002/14651858.CD012661.pub2
  9. Demidova T.Yu., Izmailova M.Ya. The structure of the prevalence of cardiovascular diseases and chronic kidney disease in patients with type 2 diabetes mellitus in the stationary care. Therapy. 2022;8:20-31.  https://doi.org/10.18565/therapy.2022.8.20-31
  10. Gastaldelli A, Gaggini M, DeFronzo RA. Role of Adipose Tissue Insulin Resistance in the Natural History of Type 2 Diabetes: Results From the San An-tonio Metabolism Study. Diabetes. 2017 Apr;66(4):815-822.  https://doi.org/10.2337/db16-1167
  11. Dedov I.I., Tkachuk V.A., Gusev N.B., et al. Type 2 diabetes and metabolic syndrome: identification of the molecular mechanisms, key signaling pathways and transcription factors aimed to reveal new therapeutical targets. Diabetes mellitus. 2018;21(5):364-375. (In Russ.) https://doi.org/10.14341/DM9730
  12. Nesic J, Ljujic B, Rosic V, et al. Adiponectin and Interleukin 33: Possible Early Markers of Metabolic Syndrome. J Clin Med. 2022 Dec 24;12(1):132.  https://doi.org/10.3390/jcm12010132
  13. Kaneva A.M., Bojko E.R. Lipid accumulation product or lap as an up-to-date clinical biochemical marker of human obesity. Health Risk Analysis. 2019, No. 2, Pp. 164–174.  https://doi.org/10.21668/health.risk/2019.2.18.eng
  14. Egorova, I.E. Role of inflammation in the pathogenesis of insulin resistance / I.E. Egorova, V.I. Bakhtairova, A.I. Suslova // Innovative technologies in pharmacy: Proceedings of the All-Russian scientific and practical conference with international participation, dedicated to the memory of Associate Professor Peshkova V.A., Irkutsk, June 20, 2018 / Ministry of Health of the Russian Federation, Irkutsk State Medical University. Volume Issue 5. – Irkutsk: Irkutsk State Medical University, 2018. – Pp. 69-72. – EDN XSSQHB. Innovative technologies in pharmacy. Irkutsk, 2018. Issue 5. (elibrary.ru)
  15. Yermolova T.V. , Yermolov S.Yu., Belyayeva Ye.L. Non-Alcoholic Fatty Liver Disease: a Modern Approach to the Problem. Effective Pharmacotherapy. Gastroenterology. 2016;5:26-35.  https://umedp.ru/upload/iblock/38d/specgepat_2016.pdf
  16. Petrov IM, Medvedeva IV, Sholomov IF, Chesnokovaet LV. Biomarkers of cardiovascular risk in patients with non-alcoholic fatty liver disease. Journal of the Grodno State Medical University. 2020;18(3):236-242.  https://doi.org/10.25298/2221-8785-2020-18-3-236-242
  17. Ajith TA, Jayakumar TG. Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases. World J Cardi-ol. 2014 Oct 26;6(10):1091-1099. https://doi.org/10.4330/wjc.v6.i10.1091
  18. Belskikh E.S., Zvyagina V.I., Uryasiev O.M. Modern ideas about the pathogenesis and approaches to the correction of mitochondrial dysfunction. Science of the Young (Eruditio Juvenium). 2016;1:104-112. Date of access: 28.03.2025. https://cyberleninka.ru/article/n/sovremennye-predstavleniya-o-patogeneze-i-podhodah-k-korrektsii-mitohondrialnoy-disfunktsii
  19. DiBona GF. Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens. 2002 Mar;11(2):197-200.  https://doi.org/10.1097/00041552-200203000-00011
  20. Wang ZV, Scherer PE. Adiponectin, the past two decades. J Mol Cell Biol. 2016 Apr;8(2):93-100.  https://doi.org/10.1093/jmcb/mjw011
  21. Ortega Moreno L, Copetti M, Fontana A, et al. Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes. Cardiovasc Diabetol. 2016 Jan 27;15:17.  https://doi.org/10.1186/s12933-016-0339-z
  22. Shishkova Yu.N., Minyailova N.N., Rovda Yu.I., Kazakova L.M. Mechanisms of kidney damage in obesity and metabolic syndrome (literature review). Mother and Child in Kuzbass. 2018;2(73):9-15.  https://cyberleninka.ru/article/n/mehanizmy-porazheniya-pochek-pri-ozhirenii-i-metabolicheskom-sindrome-obzor-literatury
  23. Kurkin D.V., Abrosimova E.E., Bakulin D.A., et al. The Role of the NO-Ergic System in the Regulation of Carbohydrate Metabolism and the Development of Diabetes Mellitus. Progress in Physiological Science. 2022;53(1):88-104. (In Russ.) https://doi.org/10.31857/S0301179822010052
  24. Golivets T.P., Likrizon S.V., Dubonosova D.G. Insulin resistance as a predictor of polymorbidity (review). Pathogenetic therapy. Challenges in Modern Medicine. 2022. 45(1): 5–19 (in Russ.). https://doi.org/10.52575/2687-0940-2022-45-1-5-19
  25. Ladeiras-Lopes R, Moreira HT, Bettencourt N, et al. Metabolic Syndrome Is Associated With Impaired Diastolic Function Independently of MRI-Derived Myocardial Extracellular Volume: The MESA Study. Diabetes. 2018 May;67(5):1007-1012. https://doi.org/10.2337/db17-1496
  26. Scuteri A, Franco OH, Majiid A, et al. The relationship between the metabolic syndrome and arterial wall thickness: A mosaic still to be interpreted. Atherosclerosis. 2016 Dec;255:11-16.  https://doi.org/10.1016/j.atherosclerosis.2016.10.032
  27. Algorithms of specialized medical care for patients with diabetes mellitus / Edited by I.I. Dedov, M.V. Shestakova, O.Y. Sukhareva. – 12th issue. – M.; 2025.
  28. Jacob S, Krentz AJ, Deanfield J, Rydén L. Evolution of Type 2 Diabetes Management from a Glucocentric Approach to Cardio-Renal Risk Reduction: The New Paradigm of Care. Drugs. 2021 Aug;81(12):1373-1379. https://doi.org/10.1007/s40265-021-01554-6
  29. Shishkova V.N, Kapustina L.A. Rational approach to the solution of cardiometabolic problems in the therapy of comorbid patients. Vrach. 2018; 29(11): 3–11. (In Russ.) https://doi.org/10.29296/25877305-2018-11-01
  30. Schobersberger W, Dünnwald T, Gmeiner G, Blank C. Story behind meldonium-from pharmacology to performance enhancement: a narrative review. Br J Sports Med. 2017 Jan;51(1):22-25.  https://doi.org/10.1136/bjsports-2016-096357
  31. Jaudzems K, Kuka J, Gutsaits A, Zinovjevs K, Kalvinsh I, Liepinsh E, Liepinsh E, Dambrova M. Inhibition of carnitine acetyltransferase by mildronate, a regulator of energy metabolism. J Enzyme Inhib Med Chem. 2009 Dec;24(6):1269-1275. https://doi.org/10.3109/14756360902829527
  32. Lippi G, Mattiuzzi C. Misuse of the metabolic modulator meldonium in sports. J Sport Health Sci. 2017 Mar;6(1):49-51.  https://doi.org/10.1016/j.jshs.2016.06.008
  33. Dambrova M, Makrecka-Kuka M, Vilskersts R, Makarova E, Kuka J, Liepinsh E. Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity. Pharmacol Res. 2016 Nov;113(Pt B):771-780.  https://doi.org/10.1016/j.phrs.2016.01.019
  34. Liepinsh E, Makarova E, Sevostjanovs E, et al. Carnitine and γ-Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2-mediated Transport. Basic Clin Pharmacol Toxicol. 2017 May;120(5):450-456.  https://doi.org/10.1111/bcpt.12729
  35. Liepinsh E, Skapare E, Kuka J, et al. Activated peroxisomal fatty acid metabolism improves cardiac recovery in ischemia-reperfusion. Naunyn Schmiedebergs Arch Pharmacol. 2013 Jun;386(6):541-550.  https://doi.org/10.1007/s00210-013-0849-0
  36. Dambrova M, Chlopicki S, Liepinsh E, et al. The methylester of gamma-butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):533-539.  https://doi.org/10.1007/s00210-004-0925-6
  37. Sjakste N, Gutcaits A, Kalvinsh I. Mildronate: an antiischemic drug for neurological indications. CNS Drug Rev. 2005 Summer;11(2):151-168.  https://doi.org/10.1111/j.1527-3458.2005.tb00267.x
  38. Antonova K.V., Tanashyan M.M., Raskurazhev A.A., et al. Obesity and the nervous system. Obesity and metabolism. 2024;21(1):68-78. (In Russ.) https://doi.org/10.14341/omet13019
  39. Statsenko M.E., Poletaeva L.V., Gurkina S.V. et al. Clinical efficacy of mildronate in the complex treatment of diabetic peripheral (sensorimotor) neuropathy. Clinical Medicine. 2008;86(9):67-71. 
  40. Zhu Y, Zhang G, Zhao J, et al. Efficacy and safety of mildronate for acute ischemic stroke: a randomized, double-blind, active-controlled phase II multicenter trial. Clin Drug Investig. 2013 Oct;33(10):755-60.  https://doi.org/10.1007/s40261-013-0121-x
  41. Tuo QZ, Zhang ST, Lei P. Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Med Res Rev. 2022 Jan;42(1):259-305.  https://doi.org/10.1002/med.21817
  42. Yang W, Lei X, Liu F, et al. Meldonium, as a potential neuroprotective agent, promotes neuronal survival by protecting mitochondria in cerebral ischemia-reperfusion injury. J Transl Med. 2024 Aug 15;22(1):771.  https://doi.org/10.1186/s12967-024-05222-7
  43. Dambrova M, Liepinsh E, Kalvinsh I. Mildronate: cardioprotective action through carnitine-lowering effect. Trends Cardiovasc Med. 2002 Aug;12(6):275-279.  https://doi.org/10.1016/s1050-1738(02)00175-5
  44. Sokolovska J, Isajevs S, Sugoka O, et al. Correction of glycaemia and GLUT1 level by mildronate in rat streptozotocin diabetes mellitus model. Cell Biochem Funct. 2011 Jan–Feb;29(1):55-63.  https://doi.org/10.1002/cbf.1719
  45. Dzerve V, Matisone D, Kukulis I, et al. Mildronate improves peripheral circulation in patients with chronic heart failure: results of clinical trial (the first report). Seminars in Cardiology. 2005;11(2):56-64. 
  46. Statsenko M.E., Shilina N.N., Turkina S.V. Application of meldonium in complex treatment of patients with heart failure in the early postinfarction period. Therapeutic Archive. 2014;86(4):30-35. 
  47. Statsenko ME, Turkina SV, Lopushkova YE. Are there any benefits from prescribing a cardiac cytoprotector to enhance the quality of life in patients with coronary heart disease and chronic heart failure? Meditsinskiy sovet = Medical Council. 2024;(13):24-32. (In Russ.) https://doi.org/10.21518/ms2024-264
  48. Bergman HM, Lindfors L, Palm F, Kihlberg J, Lanekoff I. Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging. Anal Bioanal Chem. 2019 May;411(13):2809-2816. https://doi.org/10.1007/s00216-019-01721-5
  49. Guasch-Ferr´e M, Ruiz-Canela M, Li J, et al. Plasma Acylcarnitines and Risk of Type 2 Diabetes in a Mediterranean Population at High Cardiovascular Risk. J Clin Endocrinol Metab. 2019 May 1;104(5):1508-1519. https://doi.org/10.1210/jc.2018-01000
  50. Liepinsh E, Konrade I, Skapare E, et al. Mildronate treatment alters γ-butyrobetaine and l-carnitine concentrations in healthy volunteers. J Pharm Pharmacol. 2011 Sep;63(9):1195-1201. https://doi.org/10.1111/j.2042-7158.2011.01325.x
  51. Degrace P, Demizieux L, Du ZY, et al. Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats. J Biol Chem. 2007 Jul 20;282(29):20816-20826. https://doi.org/10.1074/jbc.M611391200
  52. Sokolovska J, Rumaks J, Karajeva N, Grīnvalde D, Shapirova J, Kluša V, Kalvinsh I, Sjakste N. The influence of mildronate on peripheral neuropathy and some characteristics of glucose and lipid metabolism in rat streptozotocin-induced diabetes mellitus model. Biomed Khim. 2011 Sep–Oct;57(5):490-500. Russian. https://doi.org/10.18097/pbmc20115705490
  53. Liepinsh E, Skapare E, Svalbe B, Makrecka M, Cirule H, Dambrova M. Anti-diabetic effects of mildronate alone or in combination with metformin in obese Zucker rats. Eur J Pharmacol. 2011 May 11;658(2-3):277-283.  https://doi.org/10.1016/j.ejphar.2011.02.019
  54. Dambrova M, Skapare-Makarova E, Konrade I, et al. Meldonium decreases the diet-increased plasma levels of trimethylamine N oxide, a metabolite associated with atherosclerosis. J Clin Pharmacol. 2013 Oct;53(10):1095-1098. https://doi.org/10.1002/jcph.135
  55. Velasquez MT, Ramezani A, Manal A, Raj DS. Trimethylamine N-Oxide: The Good, the Bad and the Unknown. Toxins (Basel). 2016 Nov 8;8(11):326.  https://doi.org/10.3390/toxins8110326
  56. Subramaniam S, Fletcher C. Trimethylamine N oxide: breathe new life. Br J Pharmacol. 2018 Apr;175(8):1344-1353. https://doi.org/10.1111/bph.13959
  57. Geng J, Yang C, Wang B, et al. Trimethylamine N oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed Pharmacother. 2018 Jan;97:941-947.  https://doi.org/10.1016/j.biopha.2017.11.016
  58. Cheng X, Qiu X, Liu Y, Yuan C, Yang X. Trimethylamine N oxide promotes tissue factor expression and activity in vascular endothelial cells: A new link between trimethylamine N oxide and atherosclerotic thrombosis. Thromb Res. 2019 May;177:110-116.  https://doi.org/10.1016/j.thromres.2019.02.028
  59. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-585.  https://doi.org/10.1038/nm.3145
  60. Ussher JR, Lopaschuk GD, Arduini A. Gut microbiota metabolism of L carnitine and cardiovascular risk. Atherosclerosis. 2013 Dec;231(2):456-461.  https://doi.org/10.1016/j.atherosclerosis.2013.10.013
  61. Tilg H. A Gut Feeling about Thrombosis. N Engl J Med. 2016 Jun 23;374(25):2494-2496. https://doi.org/10.1056/NEJMcibr1604458
  62. Shah PK. Biomarkers of plaque instability. Curr Cardiol Rep. 2014 Dec;16(12):547.  https://doi.org/10.1007/s11886-014-0547-7
  63. Tsuboi N, Okabayashi Y. The Renal Pathology of Obesity: Structure-Function Correlations. Semin Nephrol. 2021 Jul;41(4):296-306.  https://doi.org/10.1016/j.semnephrol.2021.06.002
  64. Statsenko M.E., Belenkova S.V., Sporova O.E., Shilina N.N. Application of Mildronate in the combined therapy of chronic heart failure in the postinfarction period in patients with type 2 diabetes mellitus. Clinical Medicine. 2007;7:39-42. 
  65. Statsenko M.E., Turkina S.V., Tolstov S.N. Place of p-fox-inhibitors of free fatty acids in the combined therapy of cardiovascular complications in patients with type 2 diabetes mellitus. Russian Cardiology Journal. 2011;2(88):102-110. 
  66. Erpicum P, Rowart P, Defraigne JO, Krzesinski JM, Jouret F. What we need to know about lipid-associated injury in case of renal ischemia-reperfusion. Am J Physiol Renal Physiol. 2018 Dec 1;315(6): F1714–F1719. https://doi.org/10.1152/ajprenal.00322.2018
  67. Bagchi AK, Surendran A, Malik A, Jassal DS, Ravandi A, Singal PK. IL 10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury. Sci Rep. 2020 Jul 21;10(1):12120. https://doi.org/10.1038/s41598-020-68995-z
  68. Todorović Z, Đurašević S, Stojković M, et al. Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia-Reperfusion Injury. Int J Mol Sci. 2021 Mar 10;22(6):2798. https://doi.org/10.3390/ijms22062798
  69. Đurašević S, Stojković M, Bogdanović L, et al. The Effects of Meldonium on the Renal Acute Ischemia/Reperfusion Injury in Rats. Int J Mol Sci. 2019 Nov 15;20(22):5747. https://doi.org/10.3390/ijms20225747

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.