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VOLUME 28 , ISSUE 4 ( April, 2024 ) > List of Articles

Original Article

Effects of Glycemic Variability in Critically Ill Patients with Coronavirus Disease 2019: A Retrospective Observational Study

Emerson Boschi, Gilberto Friedman, Rafael B Moraes

Keywords : Coronavirus 2019, Critical care, Diabetes mellitus, Glycemic variability, Hyperglycemia, Respiratory distress syndrome

Citation Information : Boschi E, Friedman G, Moraes RB. Effects of Glycemic Variability in Critically Ill Patients with Coronavirus Disease 2019: A Retrospective Observational Study. Indian J Crit Care Med 2024; 28 (4):381-386.

DOI: 10.5005/jp-journals-10071-24688

License: CC BY-NC 4.0

Published Online: 30-03-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Aim and background: Hyperglycemia is considered an adaptive metabolic manifestation of stress and is associated with poor outcomes. Herein, we analyzed the association between glycemic variability (GV) and hospital mortality in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and the association between GV and mechanical ventilation (MV), ICU stay, length of hospital stays, renal replacement therapy (RRT), hypoglycemia, nosocomial infections, insulin use, and corticosteroid class. Materials and methods: In this retrospective observational study, we collected information on blood glucose levels during the first 10 days of hospitalization in a cohort of ICU patients with COVID-19 and its association with outcomes. Results: In 239 patients, an association was observed between GV and hospital mortality between the first and last quartiles among patients without diabetes [odds ratio (OR), 3.78; confidence interval, 1.24–11.5]. A higher GV was associated with a greater need for RRT (p = 0.002), regular insulin (p < 0.001), and episodes of hypoglycemia (p < 0.001). Nosocomial infections were associated with intermediate GV quartiles (p = 0.02). The corticosteroid class had no association with GV (p = 0.21). Conclusion: Glycemic variability was associated with high mortality in patients with COVID-19 and observed in the subgroup of patients without diabetes. Clinical significance: Glycemic control in critically ill patients remains controversial and hyperglycemia is associated with worse outcomes. Diabetes mellitus (DM) is one of the most prevalent comorbidities in patients with COVID-19. In addition, they require corticosteroids due to pulmonary involvement, representing a challenge and an opportunity to better understand how glycemic changes can influence the outcome of these patients.

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  1. Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet 2009;373(9677):1798–1807. DOI: 10.1016/S0140-6736 (09)60553-5.
  2. Mifsud S, Schembri EL, Gruppetta M. Stress-induced hyperglycaemia. Br J Hosp Med (Lond) 2018;79(11):634–639. DOI: 10.12968/hmed.2018.79.11.634.
  3. Kavanagh BP, McCowen KC. Clinical practice. Glycemic control in the ICU. N Engl J Med 2010;363(26):2540–2546. DOI: 10.1056/NEJMcp1001115.
  4. American Diabetes Association Professional Practice Committee. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022;45(Suppl. 1):S46–S59. DOI: 10.2337/dc22-S004.
  5. Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 2006;105:244–252. DOI: 10.1097/00000542-200608000-00006.
  6. Todi S, Bhattacharya M. Glycemic variability and outcome in critically ill. Indian J Crit Care Med 2014;18(5):285–290. DOI: 10.4103/0972-5229.132484.
  7. Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study. Crit Care 2013;17(2):R37. DOI: 10.1186/cc12547.
  8. Zhou Z, Sun B, Huang S, Zhu C, Bian M. Glycemic variability: Adverse clinical outcomes and how to improve it? Cardiovasc Diabetol 2020;19(1):102. DOI: 10.1186/s12933-020-01085-6.
  9. Krinsley JS. Glycemic variability and mortality in critically ill patients: The impact of diabetes. J Diabetes Sci Technol 2009;3(6):1292–1301. DOI: 10.1177/193229680900300609.
  10. Todi S. Glycemic control in critically ill: A moving target. Indian J Crit Care Med 2014;18(4):229–233. DOI: 10.4103/0972-5229.130574.
  11. World Health Organization. COVID-19 timeline. Pan-American Health Organization/World Health Organization. 2023. Available from:
  12. Reyes LF, Bastidas A, Narváez PO, Parra–Tanoux D, Fuentes YV, Serrano–Mayorga CC, et al. Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-COVID-19 study: A prospective, multicenter, multinational, cohort study. PLoS One 2022;17(3):e0265529. DOI: 10.1371/journal.pone.0265529.
  13. Motiaa Y, Rachidi SA, Labib S, Sbai H, Mohammed TB, Adil Z, et al. Comparison of ICU patients’ characteristics across two waves of COVID-19: A monocentric cohort study. Indian J Respir Care 202312(2):139–145. DOI: 10.5005/jp-journals-11010-1047.
  14. Coppelli A, Giannarelli R, Aragona M, Penno G, Falcone M, Tiseo G, et al. Hyperglycemia at hospital admission is associated with severity of the prognosis in patients hospitalized for COVID-19: The Pisa COVID-19 study. Diabetes Care 2020;43(10):2345–2348. DOI: 10.2337/dc20-1380.
  15. Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: The CORONADO study. Diabetologia 2020;63(8): 1500–1515. DOI: 10.1007/s00125-020-05180-x.
  16. Hartmann B, Verket M, Balfanz P, Hartmann NU, Jacobsen M, Brandts J, et al. Glycaemic variability is associated with all-cause mortality in COVID-19 patients with ARDS: A retrospective subcohort study. Sci Rep 2022;12(1):9862. DOI: 10.1038/s41598-022-13816-8.
  17. Chen L, Sun W, Liu Y, Zhang L, Lv Y, Wang Q, et al. Association of early-phase in-hospital glycemic fluctuation with mortality in adult patients with coronavirus disease 2019. Diabetes Care 2021;44(4): 865–873. DOI: 10.2337/dc20-0780.
  18. Becker CD, Sabang RL, Cordeiro MFN, Hassan IF, Goldberg MD, Scurlock CS. Hyperglycemia in medically critically ill patients: Risk factors and clinical outcomes. Am J Med 2020;33(10):e568–e574. DOI: 10.1016/j.amjmed.2020.03.012.
  19. Hespanhol V, Bárbara C. Pneumonia mortality, comorbidities matter? Pulmonology 2020;26(3):123–129. DOI: 10.1016/j.pulmoe.2019.10.003.
  20. Zou Q, Zheng S, Wang X, Liu S, Bao J, Yu F, et al. Influenza A-associated severe pneumonia in hospitalized patients: Risk factors and NAI treatments. Int J Infect Dis 2020;92:208–213. DOI: 10.1016/j.ijid.2020.01.017.
  21. Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013;495(7440):251–254. DOI: 10.1038/nature12005.
  22. Iacobellis G. COVID-19 and diabetes: Can DPP4 inhibition play a role? Diabetes Res Clin Pract 2020;162:108125. DOI: 10.1016/j.diabres.2020.108125.
  23. Remuzzi A, Remuzzi G. COVID-19 and Italy: What next? Lancet 2020;395(10231):1225–1228. DOI: 10.1016/S0140-6736 (20)30627-9.
  24. Brufsky A. Hyperglycemia, hydroxychloroquine, and the COVID-19 pandemic. J Med Virol 2020;92(7):770–775. DOI: 10.1002/jmv.25887.
  25. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021;384(8):693–704. DOI: 10.1056/NEJMoa2021436.
  26. Pretty C, Chase JG, Lin J, Shaw GM, Le Compte A, Razak N, et al. Impact of glucocorticoids on insulin resistance in the critically ill. Comput Methods Programs Biomed 2011;102(2):172–180. DOI: 10.1016/j.cmpb.2010.08.004.
  27. Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, et al. SAPS 3: From evaluation of the patient to evaluation of the intensive care unit. Part 2: development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 2005;31(10):1345–1355. DOI: 10.1007/s00134-005-2763-5.
  28. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22(7):707–710. DOI: 10.1007/BF01709751.
  29. Xie W, Wu N, Wang B, Xu Y, Zhang Y, Xiang Y, et al. Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes. Diabetes Res Clin Pract 2021;180:109041. DOI: 10.1016/j.diabres.2021.109041.
  30. Meersch M, Schmidt C, Zarbock A. Perioperative acute kidney injury: An under-recognized problem. Anesth Analg 2017;125(4):1223–1232. DOI: 10.1213/ANE.0000000000002369.
  31. Gorelik Y, Bloch–Isenberg N, Hashoul S, Heyman SN, Khamaisi M. Hyperglycemia on admission predicts acute kidney failure and renal functional recovery among inpatients. J Clin Med 2021;11(1):54. DOI: 10.3390/jcm11010054.
  32. Moriyama N, Ishihara M, Noguchi T, Nakanishi M, Arakawa T, Asaumi Y, et al. Admission hyperglycemia is an independent predictor of acute kidney injury in patients with acute myocardial infarction. Circ J 2014;78(6):1475–1480. DOI: 10.1253/circj.cj-14-0117.
  33. Ranzani OT, Bastos LSL, Gelli JGM, Marchesi JF, Baião F, Hamacher S, et al. Characterisation of the first 250 000 hospital admissions for COVID-19 in Brazil: A retrospective analysis of nationwide data. Lancet Respir Med 2021;9(4):407–418. DOI: 10.1016/S2213-2600 (20)30560-9.
  34. Plummer MP, Bellomo R, Cousins CE, Annink CE, Sundararajan K, Reddi BA, et al. Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality. Intensive Care Med 2014;40(7):973–980. DOI: 10.1007/s00134-014-3287-7.
  35. Krinsley JS. Glycemic control, diabetic status, and mortality in a heterogeneous population of critically ill patients before and during the era of intensive glycemic management: Six and one-half years experience at a university-affiliated community hospital. Semin Thorac Cardiovasc Surg 2006;18(4):317–325. DOI: 10.1053/j.semtcvs.2006.12.003.
  36. Morse J, Gay W, Korwek KM, McLean LE, Poland RE, Guy J, et al. Hyperglycaemia increases mortality risk in non-diabetic patients with COVID-19 even more than in diabetic patients. Endocrinol Diabetes Metab 2021;4(4):e00291. DOI: 10.1002/edm2.291.
  37. Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA 2020;324(13):1330–1341. DOI: 10.1001/jama.2020. 17023.
  38. Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: A triple-blinded randomized controlled trial. BMC Infect Dis 2021;21(1):337. DOI: 10.1186/s12879-021-06045-3.
  39. Yu B, Li C, Sun Y, Wang DW. Insulin treatment is associated with increased mortality in patients with COVID-19 and type 2 diabetes. Cell Metab 2021;33(1):65.e2–77.e2. DOI: 10.1016/j.cmet.2020. 11.014.
  40. Soop M, Duxbury H, Agwunobi AO, Gibson JM, Hopkins SJ, Childs C, et al. Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans. Am J Physiol Endocrinol Metab 2002;282(6):E1276–E1285. DOI: 10.1152/ajpendo.00535. 2001.
  41. Corstjens AM, Ligtenberg JJ, van der Horst IC, Spanjersberg R, Lind JS, Tulleken JE, et al. Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients. Crit Care 2006;10(5):R135. DOI: 10.1186/cc5048.
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