Combined hyperglycemic crisis: definition, diagnosis and treatment features

Mankovsky B.M., Halushko O.A., Gumenyuk M.I.
DOI : https://doi.org/10.57105/2415-7252-2025-6-01

Resume

Combined hyperglycemic crisis (CHC) is an acute and life-threatening emergency that often develops in elderly and senile patients with diabetes mellitus (DM) and leads to significant morbidity and mortality.
The aim of this review is to highlight current knowledge about the epidemiology, pathophysiology, clinical picture and recommendations for the diagnosis and treatment of combined hyperglycemic crises in patients of different ages.

Material and methods. To achieve this goal, a search and analysis of full-text articles was conducted using the PubMed, Web of Science and Scopus databases. The search was conducted using the key terms “combined hyperglycemic crisis” and “mixed hyperglycemic crisis”. It included randomized controlled trials, meta-analyses and individual book editions and covered English-language and Ukrainian-language publications over the past 25 years (from August 2000 to September 2025).

As a result of the conducted studies, it was found that against the background of acute severe hyperglycemia with osmotically stimulated diuresis, patients develop a condition characterized by: severe dehydration; high hyperglycemia (above 30 mmol/l); hyperosmolarity (over 320 mOsm/l); metabolic acidosis and ketoacidosis; significant impairment of consciousness and vital functions. The prognosis and outcome of treatment of patients with CHC are determined by the severity of dehydration, the presence of concomitant diseases and age >65 years. The article describes the features of pathogenesis, risk factors, diagnostic criteria, clinical manifestations and treatment methods of patients with CHC.

Conclusions. CHC is a formidable complication of diabetes mellitus in patients of all ages, which requires increased attention from endocrinologists, therapists, geriatricians, cardiologists, intensivists and specialists of other profiles. Severe CHC is characterized by profound dehydration, water-electrolyte imbalance, metabolic acidosis with ketosis, neurological disorders and impaired consciousness. CHC therapy should be carried out taking into account the individual characteristics of the elderly and senile patient in order to prevent the development of side effects and complications.

Keywords: diabetes mellitus, hyperglycemia, combined hyperglycemic crisis, diagnostics, treatment, intensive care

References:
  1. Міжнародна діабетична федерація (IDF Diabetes Atlas, 2025). Доступ: https://diabetesatlas.org
  2. Umpierrez G, Korytkowski M. Diabetic emergencies – ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 2016 Apr;12(4):222-32. doi: 10.1038/nrendo.2016.15.
  3. Guzmán GE, Martínez V, Romero S, Cardozo MM, Guerra MA, Arias O. Combined hyperglycemic crises in adult patients already exist in Latin America. Biomedica. 2024 May 31;44(Sp. 1):110-118. doi: 10.7705/biomedica.6912.
  4. American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S128-S145. doi: 10.2337/dc25-S006.
  5. Kao Y, Hsu CC, Weng SF, Lin HJ, Wang JJ, Su SB, Huang CC, Guo HR. Subsequent mortality after hyperglycemic crisis episode in the non-elderly: a national population-based cohort study. Endocrine. 2016 Jan;51(1):72-82. doi: 10.1007/s12020-015-0669-8.
  6. 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.
  7. Pasquel FJ, Tsegka K, Wang H, Cardona S, Galindo RJ, Fayfman M, et al. Clinical Outcomes in Patients With Isolated or Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State: A Retrospective, Hospital-Based Cohort Study. Diabetes Care. 2020 Feb;43(2):349-357. doi: 10.2337/dc19-1168.
  8. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53. doi: 10.2337/diacare.24.1.131
  9. Pal R, Banerjee M, Yadav U, Bhattacharjee S. Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature. Diabetes Metab Syndr. 2020 Nov-Dec;14(6):1563-1569. doi: 10.1016/j.dsx.2020.08.015.
  10. Chaithongdi N, Subauste JS, Koch CA, Geraci SA. Diagnosis and management of hyperglycemic emergencies. Hormones (Athens). 2011 Oct-Dec;10(4):250-60. doi: 10.14310/horm.2002.1316. PMID: 22281881.
  11. Stoner GD. Hyperosmolar Hyperglycemic State. Am Fam Physician. 2017 Dec 1;96(11):729-736. PMID: 29431405.
  12. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43. doi: 10.2337/dc09-9032.
  13. Guillermo E. Umpierrez, Mary Beth Murphy, Abbas E. Kitabchi; Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome. Diabetes Spectr 1 January 2002; 15 (1): 28–36. doi: 2337/diaspect.15.1.28
  14. Yamaoka T, Tamura Y, Kodera R, Tsuboi Y, Sato K, Chiba Y, et al. [Background characteristics and clinical features of elderly patients with hyperglycemic hyperosmolar syndrome]. Nihon Ronen Igakkai Zasshi. 2017;54(3):349-355. Japanese. doi: 10.3143/geriatrics.54.349.
  15. Rodriguez Alvarez P, San Martin VT, Morey-Vargas OL. Hyperglycemic crises in adults: A look at the 2024 consensus report. Cleve Clin J Med. 2025 Mar 3;92(3):152-158. doi: 10.3949/ccjm.92a.24089.
  16. Шлапак І.П., Маньковський Б.М., Галушко О.А., Кондрацька І.М. Інфузійна терапія в практиці лікаря-ендокринолога. К., 2016. 294 с.
  17. Маньковський Б.М., Галушко О.А., Гуменюк М.І. Невідкладні стани в осіб похилого віку: діагностика та лікування. К.: Віра Проджект, 2025. – 256 с.
  18. Маньковський Б.М., Галушко О.А., Гуменюк М.І. Гіперосмолярний гіперглікемічний стан у пацієнтів похилого і старечого віку. Діабет, ожиріння, метаболічний синдром, 2025, 4: 42-52. https://doi.org/10.57105/2415-7252-2025-4-02
  19. Mustafa OG, Haq M, Dashora U, Castro E, Dhatariya KK; Joint British Diabetes Societies (JBDS) for Inpatient Care Group. Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group. Diabet Med. 2023 Mar;40(3):e15005. doi: 10.1111/dme.15005.
  20. Umpierrez G, Freire AX. Abdominal pain in patients with hyperglycemic crises. J Crit Care. 2002 Mar;17(1):63-7. doi: 10.1053/jcrc.2002.33030.
  21. Hassan EM, Mushtaq H, Mahmoud EE, Chhibber S, Saleem S, Issa A, et al. Overlap of diabetic ketoacidosis and hyperosmolar hyperglycemic state. World J Clin Cases. 2022 Nov 16;10(32):11702-11711. doi: 10.12998/wjcc.v10.i32.11702.
  22. Singh B, Kaur P, Majachani N, Patel P, Reid RR, Maroules M. COVID-19 and Combined Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Nonketotic Coma: Report of 11 Cases. J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:23247096211021231. doi: 10.1177/23247096211021231.
  23. Dhatariya K, Mustafa O, Stathi D. Hyperglycemic Crises. 2025 Jun 10. In: Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G, et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905280.
  24. Галушко О. А. Гіпофосфатемія у пацієнтів відділень інтенсивної терапії: огляд літератури і власний досвід // Збірник наукових праць співробітників НМАПО ім. П. Л. Шупика, 2014, Вип.23(2): 602-613. Режим доступу: http://nbuv.gov.ua/UJRN/Znpsnmapo_2014_23(2)__83.
  25. Dhatariya KK; Joint British Diabetes Societies for Inpatient Care. The management of diabetic ketoacidosis in adults-An updated guideline from the Joint British Diabetes Society for Inpatient Care. Diabet Med. 2022 Jun;39(6):e14788. doi: 10.1111/dme.14788.
  26. Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. Med Clin North Am. 2017 May;101(3):587-606. doi: 10.1016/j.mcna.2016.12.011.
  27. Kaser S, Sourij H, Clodi M, Schneeweiß B, Laggner AN, Luger A. Treatment of acute diabetic metabolic crises in adults (Update 2023): Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorder. Wien Klin Wochenschr. 2023 Jan;135(Suppl 1):237-241. German. doi: 10.1007/s00508-023-02174-8.
  28. Alghamdi NA, Major P, Chaudhuri D, Tsui J, Brown B, Self WH, et al. Saline Compared to Balanced Crystalloid in Patients With Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Explor. 2022 Jan 6;4(1):e0613. doi: 10.1097/CCE.0000000000000613.
  29. Van Zyl DG, Rheeder P, Delport E. Fluid management in diabetic-acidosis–Ringer’s lactate versus normal saline: a randomized controlled trial. QJM. 2012 Apr;105(4):337-43. doi: 10.1093/qjmed/hcr226.
  30. Kreider KE, Gabrielski AA, Hammonds FB. Hyperglycemia Syndromes. Nurs Clin North Am. 2018 Sep;53(3):303-317. doi: 10.1016/j.cnur.2018.04.001.
  31. Dhatariya KK. Defining and characterising diabetic ketoacidosis in adults. Diabetes Res Clin Pract. 2019 Sep;155:107797. doi: 10.1016/j.diabres.2019.107797.
  32. Dhatariya KK, Nunney I, Higgins K, Sampson MJ, Iceton G. National survey of the management of Diabetic Ketoacidosis (DKA) in the UK in 2014. Diabet Med. 2016 Feb;33(2):252-60. doi: 10.1111/dme.12875.
  33. Venkatraman R, Singhi SC. Hyperglycemic hyperosmolar nonketotic syndrome. Indian J Pediatr. 2006 Jan;73(1):55-60. doi: 10.1007/BF02758261.
  34. Aldhaeefi M, Aldardeer NF, Alkhani N, Alqarni SM, Alhammad AM, Alshaya AI. Updates in the Management of Hyperglycemic Crisis. Front Clin Diabetes Healthc. 2022 Feb 9;2:820728. doi: 10.3389/fcdhc.2021.820728.
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Published
2025

How to Cite

Mankovsky B.M., Halushko O.A., Gumenyuk M.I.(2025). Combined hyperglycemic crisis: definition, diagnosis and treatment features. Diabetes Obesity Metabolic Syndrome. 6(14), 53-62.