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Cited by 163Hyperglycemia and glycemic control in critically ill and hospitalized patientsDiabetes Management and ResearchClinical Nutrition and Gastroenterology

Tight blood-glucose control without early parenteral nutrition in the ICU

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Gunst, Jan, Debaveye, Yves, Güiza, Fabian, Dubois, Jasperina, De Bruyn, Astrid, Dauwe, Dieter, De Troy, Erwin, Casaer, Michael P. +27 more·2023·New England Journal of Medicine
DOI 10.1056/nejmoa2304855
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Abstract

BACKGROUND: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).

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  • Several multicenter studies, including the NICE-SUGAR trial, in critically ill hospitalized individuals in medical and surgical ICUs failed to replicate the Van den Berghe data.

    “However, several multicenter studies, including the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial, in critically ill hospitalized individuals in medical and surgical ICUs (29-31) failed to replicate these data.”

    From 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026 (2026) · cites this paper as [30]

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  1. Kosiborod M, Rathore SS, Inzucchi SE, et al. Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. Circulation 2005;111:3078-3086.
  2. Krinsley JS, Egi M, Kiss A, et al. 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:R37.
  3. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359-1367.
  4. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-461.
  5. Vlasselaers D, Milants I, Desmet L, et al. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet 2009;373:547-556.
  6. Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 2009;35:1738-1748.
  7. Bilotta F, Caramia R, Paoloni FP, Delfini R, Rosa G. Safety and efficacy of intensive insulin therapy in critical neurosurgical patients. Anesthesiology 2009;110:611-619.
  8. Finfer S, Blair D, Bellomo R, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-1297.
  9. Kalfon P, Giraudeau B, Ichai C, et al. Tight computerized versus conventional glucose control in the ICU: a randomized controlled trial. Intensive Care Med 2014;40:171-181.
  10. Okabayashi T, Shima Y, Sumiyoshi T, et al. Intensive versus intermediate glucose control in surgical intensive care unit patients. Diabetes Care 2014;37:1516-1524.
  11. Vanhorebeek I, De Vos R, Mesotten D, Wouters PJ, De Wolf-Peeters C, Van den Berghe G. Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients. Lancet 2005;365:53-59.
  12. Ellger B, Debaveye Y, Vanhorebeek I, et al. Survival benefits of intensive insulin therapy in critical illness -Impact of maintaining normoglycemia versus glycemia- independent actions of insulin. Diabetes 2006;55:1096-1105.
  13. Vanhorebeek I, Gunst J, Ellger B, et al. Hyperglycemic kidney damage in an animal model of prolonged critical illness. Kidney Int 2009;76:512-520.
  14. Vanhorebeek I, Ellger B, De Vos R, et al. Tissue-specific glucose toxicity induces mitochondrial damage in a burn injury model of critical illness. Crit Care Med 2009;37:1355-1364.
  15. Finfer S, Liu B, Chittock DR, et al. Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012;367:1108-1118.
  16. Van den Berghe G, Schetz M, Vlasselaers D, et al. Intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target? J Clin Endocrinol Metab 2009;94:3163-3170.
  17. Hirsch IB. Understanding low sugar from NICE-SUGAR. N Engl J Med 2012;367:1150-1152.
  18. Fivez T, Kerklaan D, Mesotten D, et al. Early versus late parenteral nutrition in critically ill children. N Engl J Med 2016;374:1111-1122.
  19. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell 2011;147:728-741.
  20. Mizushima N, Levine B. Autophagy in human diseases. N Engl J Med 2020;383:1564- 1576.
  21. Hermans G, Casaer MP, Clerckx B, et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. Lancet Respir Med 2013;1:621-629.
  22. Van Herpe T, Mesotten D, Wouters PJ, et al. LOGIC-Insulin algorithm-guided versus nurse-directed blood glucose control during critical illness: the LOGIC-1 single-center, randomized, controlled clinical trial. Diabetes Care 2013;36:188-194.
  23. Dubois J, Van Herpe T, van Hooijdonk RT, et al. Software-guided versus nurse-directed blood glucose control in critically ill patients: the LOGIC-2 multicenter randomized controlled clinical trial. Crit Care 2017;21:212.
  24. Gunst J, Mebis L, Wouters PJ, et al. Impact of tight blood glucose control within normal fasting ranges with insulin titration prescribed by the Leuven algorithm in adult critically ill patients: the TGC-fast randomized controlled trial. Trials 2022;23:788.
  25. Andersen PK, Abildstrom SZ, Rosthøj S. Competing risks as a multi-state model. Stat Methods Med Res 2002;11:203-215.
  26. Krinsley JS, Chase JG, Gunst J, et al. Continuous glucose monitoring in the ICU: clinical considerations and consensus. Crit Care 2017;21:197.
  27. Oddo M, Schmidt JM, Mayer SA, Chioléro RL. Glucose control after severe brain injury. Curr Opin Clin Nutr Metab Care 2008;11:134-139.
  28. Johnston KC, Bruno A, Pauls Q, et al. Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: the SHINE randomized clinical trial. JAMA 2019;322:326-335.
  29. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-383.
  30. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-810.
  31. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13(10):818-829.
  32. Van den Berghe G. How does blood glucose control with insulin save lives in intensive care? J Clin Invest 2004;114:1187-1195.
  33. Suh SW, Gum ET, Hamby AM, Chan PH, Swanson RA. Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. J Clin Invest 2007;117:910-918.
  34. Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 2005;64:1348-1353.
  35. Sonneville R, Vanhorebeek I, den Hertog HM, et al. Critical illness-induced dysglycemia and the brain. Intensive Care Med 2015;41:192-202.
  36. Gray CS, Hildreth AJ, Sandercock PA, et al. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 2007;6:397-406.

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Authors
Gunst, J., Debaveye, Y., Güiza, F., Dubois, J., De Bruyn, A., Dauwe, D., De Troy, E., Casaer, M. P., De Vlieger, G., Haghedooren, R., Jacobs, B., Meyfroidt, G., Ingels, C., Muller, J., Vlasselaers, D., Desmet, L., Mebis, L., Wouters, P. J., Stessel, B., Geebelen, L., Vandenbrande, J., Brands, M., Gruyters, I., Geerts, E., De Pauw, I., Vermassen, J., Peperstraete, H., Hoste, E., De Waele, J. J., Herck, I., Depuydt, P., Wilmer, A., Hermans, G., Benoit, D. D., & Van den Berghe, G.
Affiliations
  • Jessa Hospital (BE)
  • From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) — all in Belgium.
  • Ghent University Hospital (BE)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2023-09-28
Volume
389
Issue
13
Pages
1180-1190
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2304855
OpenAlex
W4387077678
Cited by
163
References
3
Citations by year
2026: 43 · 2025: 51 · 2024: 63 · 2023: 6
FWCI
33.85
Type
journal article
Language
en
Open access
Licence
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
  • Document Server@UHasselt (UHasselt) (submittedVersion)
  • Lirias (submittedVersion)
Funders
  • Private Funding (Anonymous Donation from a Dutch Family to dr. Van)
  • Fonds Wetenschappelijk Onderzoek (Senior Clinical Investigator fellowship to Drs Cas, TBM T003617N to Drs. Van den Berghe, Gunst and Ben)
  • Vlaamse Overheid (Methusalem grant METH14/06 via KU Leuven to Dr. Va)
  • H2020 European Research Council (AdvG-2017-785809 to dr. Van den Berghe)
  • Universitaire Ziekenhuizen Leuven, KU Leuven (Doctoral and post-doctoral fellowships to drs. De)
  • Universitair Ziekenhuis Gent (Type 2 project Fund for innovation and clinical re)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
Keywords
tight glycemic control, intensive care unit, early parenteral nutrition, insulin therapy, insulin-induced hypoglycemia, critically ill patients, ICU length of stay, 90-day mortality, acute kidney injury, cholestatic liver dysfunction, infection incidence, respiratory support duration, protocol adherence
MeSH terms
Glycemic Control, Algorithms, Blood Glucose, Glucose, Humans, Hypoglycemia, Insulin, Intensive Care Units, Parenteral Nutrition, Critical Illness

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