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Glycemic control and intensive insulin therapy in critical illness

Renee D Stapleton, MD, PhD
Daren K Heyland, MD, FRCPC, MSc
Section Editors
Polly E Parsons, MD
Adrienne G Randolph, MD, MSc
Deputy Editor
Geraldine Finlay, MD


Hyperglycemia associated with critical illness (also called stress hyperglycemia or stress diabetes) is a consequence of many factors, including increased cortisol, catecholamines, glucagon, growth hormone, gluconeogenesis, and glycogenolysis [1]. Insulin resistance may also be a contributing factor, since it has been demonstrated in more than 80 percent of critically ill patients [2].

Hyperglycemia was previously considered an adaptive response essential for survival and was not routinely controlled in intensive care units (ICU) [3,4]. However, uncontrolled hyperglycemia is associated with poor outcomes has prompted efforts to routinely correct and prevent hyperglycemia in critically ill patients.

Glycemic control in critically ill patients is discussed in this topic review. Nutritional support in critically ill patients is described separately. (See "Nutrition support in critically ill patients: An overview".)


There is a wealth of observational evidence from different patient populations demonstrating that hyperglycemia is associated with poor clinical outcomes in critically ill patients. However, this evidence does not prove that hyperglycemia causes poor clinical outcomes, since hyperglycemia may merely be a marker of severe illness.

Trauma — Patients who are hyperglycemic following trauma have an increased mortality rate, hospital length of stay, ICU length of stay, and incidence of nosocomial infection [5-8]. This was illustrated by a prospective cohort study of 1003 patients who were admitted to an ICU following trauma [7]. Hyperglycemia (blood glucose ≥200 mg/dL [12.2 mmol/L]) was present in 255 patients (25 percent) at the time of ICU admission. Compared to normoglycemic patients, hyperglycemic patients had a significantly increased mortality rate (26 versus 12 percent) and incidence of nosocomial infection (52 versus 32 percent).

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Literature review current through: Oct 2017. | This topic last updated: Oct 31, 2017.
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  1. McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin 2001; 17:107.
  2. Saberi F, Heyland D, Lam M, et al. Prevalence, incidence, and clinical resolution of insulin resistance in critically ill patients: an observational study. JPEN J Parenter Enteral Nutr 2008; 32:227.
  3. Chinsky K. The evolving paradigm of hyperglycemia and critical illness. Chest 2004; 126:674.
  4. Robinson LE, van Soeren MH. Insulin resistance and hyperglycemia in critical illness: role of insulin in glycemic control. AACN Clin Issues 2004; 15:45.
  5. Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia as a prognostic indicator in trauma. J Trauma 2003; 55:33.
  6. Laird AM, Miller PR, Kilgo PD, et al. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma 2004; 56:1058.
  7. Sung J, Bochicchio GV, Joshi M, et al. Admission hyperglycemia is predictive of outcome in critically ill trauma patients. J Trauma 2005; 59:80.
  8. Bochicchio GV, Sung J, Joshi M, et al. Persistent hyperglycemia is predictive of outcome in critically ill trauma patients. J Trauma 2005; 58:921.
  9. Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000; 46:335.
  10. Jeremitsky E, Omert LA, Dunham CM, et al. The impact of hyperglycemia on patients with severe brain injury. J Trauma 2005; 58:47.
  11. Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc 2003; 78:1471.
  12. Falciglia M, Freyberg RW, Almenoff PL, et al. Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis. Crit Care Med 2009; 37:3001.
  13. Li Y, Bai Z, Li M, et al. U-shaped relationship between early blood glucose and mortality in critically ill children. BMC Pediatr 2015; 15:88.
  14. Qaseem A, Humphrey LL, Chou R, et al. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2011; 154:260.
  15. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359.
  16. Likosky DS, Nugent WC, Clough RA, et al. Comparison of three measurements of cardiac surgery mortality for the Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg 2006; 81:1393.
  17. Becker ER, McPherson MA, Rahimi A. Influence of source and type of admission on in-hospital mortality for coronary artery bypass surgery patients: national results from 1.7 million CABG patients, 1998 to 2002. J Card Surg 2007; 22:203.
  18. Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009; 180:821.
  19. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283.
  20. Agus MS, Steil GM, Wypij D, et al. Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med 2012; 367:1208.
  21. 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.
  22. Jeschke MG, Kulp GA, Kraft R, et al. Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial. Am J Respir Crit Care Med 2010; 182:351.
  23. Macrae D, Grieve R, Allen E, et al. A randomized trial of hyperglycemic control in pediatric intensive care. N Engl J Med 2014; 370:107.
  24. Srinivasan V, Agus MS. Tight glucose control in critically ill children--a systematic review and meta-analysis. Pediatr Diabetes 2014; 15:75.
  25. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354:449.
  26. Heyland DK, Dhaliwal R, Drover JW, et al. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 2003; 27:355.
  27. Published version of the clinical practice guidelines. In: Nutrition CPGs. www.criticalcarenutrition.com (Accessed on October 14, 2008).
  28. COIITSS Study Investigators, Annane D, Cariou A, et al. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 2010; 303:341.
  29. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125.
  30. 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.
  31. Arabi YM, Dabbagh OC, Tamim HM, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med 2008; 36:3190.
  32. Yu WK, Li WQ, Wang XD, et al. [Influence and mechanism of a tight control of blood glucose by intensive insulin therapy on human sepsis]. Zhonghua Wai Ke Za Zhi 2005; 43:29.
  33. Savioli M, Cugno M, Polli F, et al. Tight glycemic control may favor fibrinolysis in patients with sepsis. Crit Care Med 2009; 37:424.
  34. 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.
  35. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 2008; 300:933.
  36. Marik PE, Preiser JC. Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest 2010; 137:544.
  37. Kansagara D, Fu R, Freeman M, et al. Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med 2011; 154:268.
  38. NICE-SUGAR Study Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group and the Canadian Critical Care Trials Group, Finfer S, Chittock D, et al. Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study. Intensive Care Med 2015; 41:1037.
  39. Agus MS, Wypij D, Hirshberg EL, et al. Tight Glycemic Control in Critically Ill Children. N Engl J Med 2017; 376:729.
  40. Grey NJ, Perdrizet GA. Reduction of nosocomial infections in the surgical intensive-care unit by strict glycemic control. Endocr Pract 2004; 10 Suppl 2:46.
  41. Vanhorebeek I, Langouche L, Van den Berghe G. Tight blood glucose control with insulin in the ICU: facts and controversies. Chest 2007; 132:268.
  42. Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med 2007; 35:2262.
  43. Dowdy DW, Dinglas V, Mendez-Tellez PA, et al. Intensive care unit hypoglycemia predicts depression during early recovery from acute lung injury. Crit Care Med 2008; 36:2726.
  44. Hermanides J, Bosman RJ, Vriesendorp TM, et al. Hypoglycemia is associated with intensive care unit mortality. Crit Care Med 2010; 38:1430.
  45. The NICE-SUGAR Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012; 367:1108.
  46. Van den Berghe G, Wilmer A, Milants I, et al. Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm. Diabetes 2006; 55:3151.
  47. Mackenzie I, Ingle S, Zaidi S, Buczaski S. Hypoglycemia? So what! Intensive Care Med 2006; 32:620.
  48. Arnold P, Paxton RA, McNorton K, et al. The effect of a hypoglycemia treatment protocol on glycemic variability in critically ill patients. J Intensive Care Med 2015; 30:156.
  49. Jacobi J, Bircher N, Krinsley J, et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med 2012; 40:3251.
  50. Dickerson RN, Wilson VC, Maish GO 3rd, et al. Transitional NPH insulin therapy for critically ill patients receiving continuous enteral nutrition and intravenous regular human insulin. JPEN J Parenter Enteral Nutr 2013; 37:506.
  51. Bochicchio GV, Nasraway S, Moore L, et al. Results of a multicenter prospective pivotal trial of the first inline continuous glucose monitor in critically ill patients. J Trauma Acute Care Surg 2017; 82:1049.
  52. Garingarao CJ, Buenaluz-Sedurante M, Jimeno CA. Accuracy of point-of-care blood glucose measurements in critically ill patients in shock. J Diabetes Sci Technol 2014; 8:937.
  53. Okabayashi T, Shima Y. Are closed-loop systems for intensive insulin therapy ready for prime time in the ICU? Curr Opin Clin Nutr Metab Care 2014; 17:190.