Keywords
lactic acid
lactic acidosis
diagnostics
treatment
Abstract
Abstract Lactic acidosis is a nonspecific syndrome that develops in a number of severe diseases, when prerequisites are created for increased formation and accumulation of lactic acid in the blood and peripheral tissues. It can occur due to increased production or decreased excretion of lactate, as well as in the case of a combination of both reasons.
The aim of this review is to highlight current knowledge about the epidemiology, pathophysiology, clinical picture and recommendations for the diagnosis and treatment of lactic acidosis in patients with diabetes mellitus (DM).
Material and methods To achieve the goal, a search and analysis of full-text articles was conducted using the PubMed, Web of Science and Scopus databases using the key terms “lactic acidosis” and “diabetic patients”. It included randomized controlled trials, meta-analyses and individual book editions and covered English- and Ukrainian-language publications over the past 25 years (from January 2001 to February 2026).
Results Lactic acidosis is divided into types depending on the presence or absence of hypoxia. There are various mechanisms that can cause hyperlactatemia, which leads to the classification of lactic acidosis into types A, B or D. In diabetic patients, lactic acidosis may develop due to the use of metformin - metformin-associated lactic acidosis. In the treatment of patients with lactic acidosis, the first step is to restore tissue perfusion after hemodynamic disturbances. In the case of ineffective etiotropic therapy, measures to eliminate acidosis become of primary importance. In parallel, other metabolic disorders are corrected, hypotension is eliminated, microcirculation disorders, anemia, hypoxia are corrected.
Conclusion Lactic acidosis is a severe nonspecific complication of DM. The development of lactic acidosis can be provoked by heart, lung, kidney failure, liver disease with impaired function, shock, blood loss, poisoning, chronic alcoholism, etc. In the treatment of patients with lactic acidosis, the identification and elimination of its causes should be carried out as soon as possible. For the prevention of metformin-associated lactic acidosis in critically ill patients with DM type 2, insulin, not metformin, should be used to compensate for the level of glycemia.
References
1. Міжнародна діабетична федерація (IDF Diabetes Atlas, 2025). Доступ: https://diabetesatlas.org
2. Umpierrez GE, Davis GM, ElSayed NA, Fadini GP, Galindo RJ, Hirsch IB, et al. Hyperglycaemic crises in adults with diabetes: a consensus report. Diabetologia. 2024 Aug;67(8):1455-1479. doi: 10.1007/s00125-024-06183-8
3. Mankovsky B.M., Halushko O.A., Gumenyuk M.I. Nevid- kladni stany v osib pokhyloho viku: diahnostyka ta likuvan- nya [Emergency conditions in the elderly: diagnostics and treatment]. Kyiv, 2025. – 256 p. In Ukrainian.
4. Kalendar znamennykh dat i podiy v anesteziolohiyi ta me- dytsyni nevidkladnykh staniv [Calendar of significant dates and events in anesthesiology and emergency medicine] / Ed. O.A. Halushko. Kyiv, 2022. - 248 p. In Ukrainian.
5. Matyukhin I, Patschan S, Ritter O, Patschan D. Etiology and Management of Acute Metabolic Acidosis: An Update. Kidney Blood Press Res. 2020;45(4):523-531. doi: 10.1159/000507813
6. Doherty JR, Cleveland JL. Targeting lactate metabolism for cancer therapeutics. J Clin Invest. 2013 Sep;123(9):3685-92. doi: 10.1172/JCI69741
7. van Hall G. Lactate kinetics in human tissues at rest and during exercise. Acta Physiol (Oxf). 2010 Aug;199(4):499-508. doi: 10.1111/j.1748-1716.2010.02122.x
8. Kruse O, Grunnet N, Barfod C. Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. Scand J Trauma Resusc Emerg Med. 2011 Dec 28;19:74. doi: 10.1186/1757-7241-19-74
9. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014 Dec 11;371(24):2309-19. doi: 10.1056/NEJMra1309483
10. Barr D.P., Himwich H.E., Green R.P. Studies in the physiology of muscular exercise. 1. Changes in acid-base equilibrium following short periods of vigorous muscular exercise. Journal of Biological Chemistry, Volume 55, Issue 3, 1923: 495-523, https://doi.org/10.1016/S0021-9258(18)85668-X
11. Tronko M.D., Bolshova O.V., Tkach S.M. Mala entsyklope- diya endokrynoloha [Small encyclopedia of an endocrinolo- gist]. Kyiv: Medicine, 2022. – 424 p. In Ukrainian
12. Kamel KS, Oh MS, Halperin ML. L-lactic acidosis: pathophysiology, classification, and causes; emphasis on biochemical and metabolic basis. Kidney Int. 2020 Jan;97(1):75-88. doi: 10.1016/j.kint.2019.08.023
13. English P., Williams G. Hyperglycaemic crises and lactic acidosis in diabetes mellitus. Postgrad Med J 2004; 80. –Р. 253-261.
14. Zanza C, Facelli V, Romenskaya T, Bottinelli M, Caputo G, Piccioni A, et al. Lactic Acidosis Related to Pharmacotherapy and Human Diseases. Pharmaceuticals (Basel). 2022 Nov 30;15(12):1496. doi: 10.3390/ph15121496
15. Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006 Feb;10(1):R22. doi: 10.1186/cc3987
16. Eraky AM, Yerramalla Y, Khan A, Mokhtar Y, Wright A, Alsabbagh W, et al. Complexities, Benefits, Risks, and Clinical Implications of Sodium Bicarbonate Administration in Critically Ill Patients: A State-of-the-Art Review. J Clin Med. 2024 Dec 21;13(24):7822. doi: 10.3390/jcm13247822
17. Rybicki Z. Adult Intensive Care in Clinical Practice [Intensywna terapia dorosłych w praktyce klinicznej] – 4th ed, Warsaw: Makmed, 2022. – 1088 pp.
18. Filimonov V.I., Marakushin D.I. Klinichna fiziolohiya [Clini- cal physiology]. K.: Medicine, 2022. – 776 p. In Ukrainian
19. Pohanka M. D-Lactic Acid as a Metabolite: Toxicology, Diagnosis, and Detection. Biomed Res Int. 2020 Jun 17;2020:3419034. doi: 10.1155/2020/3419034
20. Ruiz RG, Morelli A, Grieco R, Cardile S, Capriati T, Trovato CM, et al. Pre-, Pro-, Post- and Synbiotics in Pediatric Short Bowel Syndrome: A Narrative Review of Current Evidence. Children (Basel). 2026 Feb 28;13(3):349. doi: 10.3390/children13030349
21. DeGonza H, Pham TA, Elmaoued R, Alkhouri R, Castillo RO, Dharmaraj R. Small Intestinal Bacterial Overgrowth in Children with Short Bowel Syndrome. Children (Basel). 2025 Nov 16;12(11):1550. doi: 10.3390/children12111550
22. Roumie CL, Chipman J, Min JY, Hackstadt AJ, Hung AM, Greevy RA Jr, et al. Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function. JAMA. 2019 Sep 24;322(12):1167-1177. doi: 10.1001/jama.2019.13206
23. Richy FF, Sabidó-Espin M, Guedes S, Corvino FA, Gottwald-Hostalek U. Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care. 2014 Aug;37(8):2291-5. doi: 10.2337/dc14-0464
24. Manouchehri A, Rashidian H, Zakariaei Z. Severe metabolic acidosis due to massive metformin overdose in a man: a case report. Oxf Med Case Reports. 2023 May 30;2023(5):omad049. doi: 10.1093/omcr/omad049
25. Vecchio S, Giampreti A, Petrolini VM, Lonati D, Protti A, Papa P, et al. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol (Phila). 2014 Feb;52(2):129-35. doi: 10.3109/15563650.2013.860985
26. See KC. Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients. World J Diabetes. 2024 Jun 15;15(6):1178-1186. doi: 10.4239/wjd.v15.i6.1178
27. American Diabetes Association Professional Practice Committee for Diabetes. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2026. Diabetes Care. 2026 Jan 1;49(Supplement_1):S183-S215. doi: 10.2337/dc26-S009
28. Gorovenko N.G., Gumenyuk M.I., Derkach M.M. Vykorystan- 32. nya infuziynykh preparativ, shcho mistyat’ laktat, dlya korektsiyi metabolichnoho atsydozu [The use of infusion preparations containing lactate for the correction of metabolic acidosis]. Ukrainian Journal of Chemotherapy, 2008, No. 1-2: 29-33. In Ukrainian
29. Halushko O.A. Hipofosfatemiya u patsiyentiv viddilen’ inten- syvnoyi terapiyi: ohlyad literatury i vlasnyy dosvid [Hypophos- phatemia in patients in intensive care units: literature review and personal experience] / Collection of scientific works of employees of the P.L. Shupyk National Medical Academy of Postgraduate Education, 2014. – issue..23, book..2. – pp.602-613. In Ukrainian
30. See KC. Glycemic targets in critically ill adults: A mini-review. World J Diabetes. 2021 Oct 15;12(10):1719-1730. doi: 10.4239/wjd.v12.i10.1719
31. Wardi G, Holgren S, Gupta A, Sobel J, Birch A, Pearce A, et al. A Review of Bicarbonate Use in Common Clinical Scenarios. J Emerg Med. 2023 Aug;65(2):e71-e80. doi: 10.1016/j.jemermed.2023.04.012
32. Müller J, Radej J, Horak J, Karvunidis T, Valesova L, Kriz M, Matejovic M. Lactate: The Fallacy of Oversimplification. Biomedicines. 2023 Dec 1;11(12):3192. doi: 10.3390/biomedicines11123192
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