Current Diabetes Reports

, Volume 12, Issue 1, pp 101–107 | Cite as

Glycemic Targets and Approaches to Management of the Patient with Critical Illness

Hospital Management of Diabetes (M Korytkowski, Section Editor)


Hyperglycemia during critical illness is associated with adverse outcome. The proof-of-concept Leuven studies assessed causality, and revealed that targeting strict normoglycemia (80–110 mg/dL) with insulin improved outcome compared with tolerating hyperglycemia to the renal threshold (215 mg/dL). A large multicenter trial (NICE-SUGAR [Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation]) found an intermediate blood glucose target (140–180 mg/dL) safer than targeting normoglycemia. Differences in design and in execution of glycemic control at the bedside may have contributed to these results. In NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation), the blood-glucose target range in the control group was lower, there were problems to reach and maintain normoglycemia in the intervention group, and inaccurate handheld blood glucose meters and variable blood sampling sites were allowed. Inaccurate tools led to insulin-dosing errors with consequently (undetected) hypoglycemia and unacceptable blood glucose variability. Also, the studies were done superimposed upon different nutritional strategies. Thus, such differences do not allow simple, evidence-based recommendations for daily practice, but an intermediate blood glucose target may be preferable while awaiting better tools to facilitate safely reaching normoglycemia.


Hyperglycemia Critical illness Normoglycemia NICE-SUGAR Glycemic targets Stress hyperglycemia Blood glucose management 

Clinical Trial Acronyms


Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients


Comparing the Effects of Two Glucose Control Regimens by Insulin in Intensive Care Unit Patients


Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation


Volume Substitution and Insulin Therapy in Severe Sepsis



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Van Cromphaut SJ. Hyperglycaemia as part of the stress response: the underlying mechanisms. Best Pract Res Clin Anaesthesiol. 2009;23(4):375–86.PubMedCrossRefGoogle Scholar
  2. 2.
    Bagshaw SM, Egi M, George C, Bellomo R. Early blood glucose control and mortality in critically ill patients in Australia. Crit Care Med. 2009;37(2):463–70.PubMedCrossRefGoogle Scholar
  3. 3.
    Kosiborod M, Rathore SS, Inzucchi SE, Masoudi FA, Wang Y, Havranek EP, 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(23):3078–86.PubMedCrossRefGoogle Scholar
  4. 4.
    Kosiborod M, Inzucchi SE, Krumholz HM, Masoudi FA, Goyal A, Xiao L, et al. Glucose normalization and outcomes in patients with acute myocardial infarction. Arch Intern Med. 2009;169(5):438–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Deedwania P, Kosiborod M, Barrett E, Ceriello A, Isley W, Mazzone T, et al. Hyperglycemia and acute coronary syndrome: a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2008;117(12):1610–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Sinnaeve PR, Steg PG, Fox KA, Van de Werf F, Montalescot G, Granger CB, et al. Association of elevated fasting glucose with increased short-term and 6-month mortality in ST-segment elevation and non-ST-segment elevation acute coronary syndromes: the Global Registry of Acute Coronary Events. Arch Intern Med. 2009;169(4):402–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Furnary AP, Cheek DB, Holmes SC, Howell WL, Kelly SP. Achieving tight glycemic control in the operating room: lessons learned from 12 years in the trenches of a paradigm shift in anesthetic care. Semin Thorac Cardiovasc Surg. 2006;18(4):339–45.PubMedCrossRefGoogle Scholar
  8. 8.
    Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345(19):1359–67.PubMedCrossRefGoogle Scholar
  9. 9.
    McCowen KC, Friel C, Sternberg J, Chan S, Forse RA, Burke PA, et al. Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications–a randomized clinical trial. Crit Care Med. 2000;28(11):3606–11.PubMedCrossRefGoogle Scholar
  10. 10.
    Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354(5):449–61.PubMedCrossRefGoogle Scholar
  11. 11.
    Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, et al. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet. 2009;373(9663):547–56.PubMedCrossRefGoogle Scholar
  12. 12.
    Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358(2):125–39.PubMedCrossRefGoogle Scholar
  13. 13.
    Preiser JC, Devos P, Ruiz-Santana S, Melot C, Annane D, Groeneveld J, 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(10):1738–48.PubMedCrossRefGoogle Scholar
  14. 14.
    •• Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283–97. This large pragmatic multicenter trial showed that tight blood glucose control, when implemented under less controlled circumstance, increased mortality.PubMedCrossRefGoogle Scholar
  15. 15.
    •• Van den Berghe G, Schetz M, Vlasselaers D, Hermans G, Wilmer A, Bouillon R et al. Clinical review: intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target? J Clin Endocrinol Metab. 2009;94(9):3163–70. This article provides possible explanations why the benefits of the Leuven tight blood glucose control could not be confirmed in the repeat studies. PubMedCrossRefGoogle Scholar
  16. 16.
    Van den Berghe G, Mesotten D, Vanhorebeek I. Intensive insulin therapy in the intensive care unit. CMAJ. 2009;180(8):799–800.PubMedCrossRefGoogle Scholar
  17. 17.
    Mitchell I, Finfer S, Bellomo R, Higlett T. Management of blood glucose in the critically ill in Australia and New Zealand: a practice survey and inception cohort study. Intensive Care Med. 2006;32(6):867–74.PubMedCrossRefGoogle Scholar
  18. 18.
    Van den Berghe G, Wilmer A, Milants I, Wouters PJ, Bouckaert B, Bruyninckx F, et al. Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm. Diabetes. 2006;55(11):3151–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Griesdale DEG, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. Can Med Assoc J. 2009;180(8):821–7.CrossRefGoogle Scholar
  20. 20.
    Egi M, Finfer S, Bellomo R. Glycemic control in the ICU. Chest. 2011;140(1):212–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Scott MG, Bruns DE, Boyd JC, Sacks DB. Tight glucose control in the intensive care unit: are glucose meters up to the task? Clin Chem. 2009;55(1):18–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Lyon ME, DuBois JA, Fick GH, Lyon AW. Estimates of total analytical error in consumer and hospital glucose meters contributed by hematocrit, maltose, and ascorbate. J Diabetes Sci Technol. 2010;4(6):1479–94.PubMedGoogle Scholar
  23. 23.
    Mann EA, Pidcoke HF, Salinas J, Wolf SE, Wade CE, Holcomb JB. Hematocrit causes the most significant error in point of care glucometers. Crit Care Med. 2009;37(4):1530.PubMedCrossRefGoogle Scholar
  24. 24.
    Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409–17.PubMedCrossRefGoogle Scholar
  25. 25.
    Pieracci FM, Henderson P, Rodney JR, Holena DN, Genisca A, Ip I, et al. Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness. Surg Infect (Larchmt). 2009;10(1):9–19.CrossRefGoogle Scholar
  26. 26.
    Mann EA, Mora AG, Pidcoke HF, Wolf SE, Wade CE. Glycemic control in the burn intensive care unit: focus on the role of anemia in glucose measurement. J Diabetes Sci Technol. 2009;3(6):1319–29.PubMedGoogle Scholar
  27. 27.
    • Pidcoke HF, Wade CE, Mann EA, Salinas J, Cohee BM, Holcomb JB et al. Anemia causes hypoglycemia in intensive care unit patients due to error in single-channel glucometers: methods of reducing patient risk. Crit Care Med. 2010;38(2):471–6. Anemia causes a systematic error in blood glucose measurements, which may result in hypoglycemia. PubMedCrossRefGoogle Scholar
  28. 28.
    Kanji S, Buffie J, Hutton B, Bunting PS, Singh A, McDonald K, et al. Reliability of point-of-care testing for glucose measurement in critically ill adults. Crit Care Med. 2005;33(12):2778–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Cembrowski GS, Tran DV, Slater-Maclean L, Chin D, Gibney RT, Jacka M. Could susceptibility to low hematocrit interference have compromised the results of the NICE-SUGAR trial? Clin Chem. 2010;56(7):1193–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Karon BS, Boyd JC, Klee GG. Glucose meter performance criteria for tight glycemic control estimated by simulation modeling. Clin Chem. 2010;56(7):1091–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Maser RE, Butler MA, DeCherney GS. Use of arterial blood with bedside glucose reflectance meters in an intensive care unit: are they accurate? Crit Care Med. 1994;22(4):595–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36(11):3008–13.PubMedCrossRefGoogle Scholar
  33. 33.
    Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2005;19(3):178–81.PubMedCrossRefGoogle Scholar
  34. 34.
    Marik PE, Preiser JC. Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest. 2010;137(3):544–51.PubMedCrossRefGoogle Scholar
  35. 35.
    •• Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G et al. Early versus Late Parenteral Nutrition in Critically Ill Adults. N Engl J Med. 2011;365(6):506–17. This RCT showed that postponing initiation of parenteral nutrition in ICU patients to beyond the first week (late parenteral nutrition) enhanced recovery compared with “early parenteral nutrition.” PubMedCrossRefGoogle Scholar
  36. 36.
    Vanhorebeek I, Gunst J, Derde S, Derese I, Boussemaere M, Guiza F, et al. Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. J Clin Endocrinol Metab. 2011;96(4):E633–45.PubMedCrossRefGoogle Scholar
  37. 37.
    Rabinowitz JD, White E. Autophagy and metabolism. Science. 2010;330(6009):1344–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Vriesendorp TM, van Santen S, DeVries JH, de Jonge E, Rosendaal FR, Schultz MJ, et al. Predisposing factors for hypoglycemia in the intensive care unit. Crit Care Med. 2006;34(1):96–101.PubMedCrossRefGoogle Scholar
  40. 40.
    Arabi YM, Tamim HM, Rishu AH. Hypoglycemia with intensive insulin therapy in critically ill patients: predisposing factors and association with mortality. Crit Care Med. 2009;37(9):2536–44.PubMedCrossRefGoogle Scholar
  41. 41.
    Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Taori G, et al. Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc. 2010;85(3):217–24.PubMedCrossRefGoogle Scholar
  42. 42.
    Vriesendorp TM, DeVries JH, van Santen S, Moeniralam HS, de Jonge E, Roos YB, et al. Evaluation of short-term consequences of hypoglycemia in an intensive care unit. Crit Care Med. 2006;34(11):2714–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Vanhorebeek I, Gielen M, Boussemaere M, Wouters PJ, Grandas FG, Mesotten D, et al. Glucose dysregulation and neurological injury biomarkers in critically ill children. J Clin Endocrinol Metab. 2010;95(10):4669–79.PubMedCrossRefGoogle Scholar
  44. 44.
    Gielen M, Mesotten D, Brugts M, Coopmans W, Van Herck E, Vanhorebeek I, et al. Effect of intensive insulin therapy on the somatotropic axis of critically ill children. J Clin Endocrinol Metab. 2011;96(8):2558–66.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Laboratory and Department Intensive Care Medicine, Katholieke Universiteit LeuvenCatholic University of LeuvenLeuvenBelgium

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