Glucose Variability in Critically Ill Patients

  • N. A. Ali
  • J. S. Krinsley
  • J.-C. Preiser


The presence of stress-induced hyperglycemia in critically ill patients, especially in those without evidence of antecedent diabetes, is a well established marker of poor outcomes [1, 2, 3, 4]. Two large single center studies comparing the standard strategy of permissive hyperglycemia to use of intravenous insulin to achieve a blood glucose between 80 and 110 mg/dl (intensive insulin therapy) demonstrated overall clinical benefit with the intensive insulin therapy [5, 6]. However, more recent studies of insulin therapy in critically ill patients have yielded conflicting results [7]. In addition, a growing awareness of the potential risks of hypoglycemia, which can occur more frequently when using intravenous insulin therapy, has raised concerns over the best way to control glucose. Despite this, reverting back to allowing hyperglycemia to continue unchecked is unlikely to be the correct approach either.


Insulin Therapy Intensive Insulin Therapy Glycemic Variability Glucose Variability Tight Glucose Control 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ali NA, O’Brien JM Jr, Blum W, et al (2007) Hyperglycemia in patients with acute myeloid leukemia is associated with increased hospital mortality. Cancer 110: 96–102CrossRefPubMedGoogle Scholar
  2. 2.
    Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE (2002) Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 87: 978–982CrossRefPubMedGoogle Scholar
  3. 3.
    Norhammar A, Tenerz A, Nilsson G, et al (2002) Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 359: 2140–2144CrossRefPubMedGoogle Scholar
  4. 4.
    Silverman RA, Pahk R, Carbone M, et al (2006) The Relationship of Plasma Glucose and HbA1c Levels among Emergency Department Patients with No Prior History of Diabetes Mellitus. Acad Emerg Med 13: 722–726CrossRefPubMedGoogle Scholar
  5. 5.
    Van den Berghe G, Wouters P, Weekers F, et al (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345: 1359–1367CrossRefPubMedGoogle Scholar
  6. 6.
    Van den Berghe G, Wilmer A, Hermans G, et al (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354: 449–461CrossRefPubMedGoogle Scholar
  7. 7.
    Brunkhorst FM, Engel C, Bloos F, et al (2008) Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis. N Engl J Med 358: 125–139CrossRefPubMedGoogle Scholar
  8. 8.
    Wilson M, Weinreb J, Hoo GW (2007) Intensive insulin therapy in critical care: A review of 12 protocols. Diabetes Care. 30: 1005–1011CrossRefPubMedGoogle Scholar
  9. 9.
    Morris AH, Orme JF Jr, Truwit JD, et al (2008) A replicable method for blood glucose control in critically Ill patients. Crit Care Med 36: 1787–1795CrossRefPubMedGoogle Scholar
  10. 10.
    Marik PE, Raghavan M (2004) Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intensive Care Med 30: 748–756CrossRefPubMedGoogle Scholar
  11. 11.
    McCowen KC, Malhotra A, Bistrian BR (2001) Stress-induced hyperglycemia. Critical care clinics 17: 107–124CrossRefPubMedGoogle Scholar
  12. 12.
    Wahl WL, Taddonio M, Maggio PM, Arbabi S, Hemmila MR. (2008) Mean glucose values predict trauma patient mortality. J Trauma 65: 42–48CrossRefPubMedGoogle Scholar
  13. 13.
    Krinsley JS (2004) Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 79: 992–1000CrossRefPubMedGoogle Scholar
  14. 14.
    Preiser JC, Devos P (2008) Clinical experience with tight glucose control by intensive insulin therapy. Crit Care Med 35:S503–S507CrossRefGoogle Scholar
  15. 15.
    Van den Berghe G, Wilmer A, Milants I, et al (2006) Intensive insulin therapy in mixed medical/ surgical intensive care units: benefit versus harm. Diabetes 55: 3151–3159CrossRefPubMedGoogle Scholar
  16. 16.
    Egi M, Bellomo R, Stachowski E, et al (2008) Blood glucose concentration and outcome of critical illness: the impact of diabetes. Crit Care Med 36: 2249–2255CrossRefPubMedGoogle Scholar
  17. 17.
    Krinsley JS (2006) 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 18: 317–325CrossRefPubMedGoogle Scholar
  18. 18.
    Devos P, Preiser JC, Melot C (2007) Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the Glucontrol study. Intensive Care Med 33 (Suppl 2): S189 (abst)Google Scholar
  19. 19.
    Ryan EA, Shandro T, Green K, et al (2004) Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 53: 955–962CrossRefPubMedGoogle Scholar
  20. 20.
    Kovatchev BP, Otto E, Cox D, Gonder-Frederick L, Clarke W (2006) Evaluation of a new measure of blood glucose variability in diabetes. Diabetes Care 29: 2433–2438CrossRefPubMedGoogle Scholar
  21. 21.
    Egi M, Bellomo R, Stachowski E, French CJ, Hart G (2006) Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 105: 244–252CrossRefPubMedGoogle Scholar
  22. 22.
    Krinsley JS (2008) Glycemic variability: A strong independent predictor of mortality in critically ill patients. Crit Care Med 36: 3008–3013CrossRefPubMedGoogle Scholar
  23. 23.
    Dossett LA, Cao H, Mowery NT, Dortch MJ, Morris JM Jr, May AK (2008) Blood glucose variability is associated with mortality in the surgical intensive care unit. Am Surg 74: 679–685PubMedGoogle Scholar
  24. 24.
    Hirshberg E, Larsen G, Van Duker H (2008) Alterations in glucose homeostasis in the pediatric intensive care unit: Hyperglycemia and glucose variability are associated with increased mortality and morbidity. Pediatr Crit Care Med 9: 361–366CrossRefPubMedGoogle Scholar
  25. 25.
    Wintergerst KA, Buckingham B, Gandrud L, Wong BJ, Kache S, Wilson DM (2006) Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics 118: 173–179CrossRefPubMedGoogle Scholar
  26. 26.
    Ali NA, O’Brien JM Jr, Dungan K, et al (2008) Glucose variability and mortality in patients with sepsis. Crit Care Med 36: 2316–2321CrossRefPubMedGoogle Scholar
  27. 27.
    Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A (2001) Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab 281: E924–E930PubMedGoogle Scholar
  28. 28.
    Collier B, Dossett LA, May AK, Diaz JJ (2008) Glucose control and the inflammatory Response. Nutr Clin Pract 23: 3–15CrossRefPubMedGoogle Scholar
  29. 29.
    Otto N, Schindler R, Lun A, Boenisch O, Frei U, Oppert M (2008) Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitro. Crit Care 12:R107CrossRefPubMedGoogle Scholar
  30. 30.
    Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ (2005) Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 64: 1348–1353PubMedGoogle Scholar
  31. 31.
    Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: A systematic overview. Stroke 32: 2426–2432CrossRefPubMedGoogle Scholar
  32. 32.
    Schiekofer S, Andrassy M, Chen J, et al (2003) Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor aB in PBMCs. Diabetes 52: 621–633CrossRefPubMedGoogle Scholar
  33. 33.
    Monnier L, Mas E, Ginet C, et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295: 1681–1687CrossRefPubMedGoogle Scholar
  34. 34.
    Holtfreter B, Bandt C, Kuhn SO, et al (2006) Serum osmolality and outcome in intensive care unit patients. Acta Anaesthesiol Scand 50: 970–977CrossRefPubMedGoogle Scholar
  35. 35.
    Dungan K, Chapman J, Braithwaite SS, Buse J (2007) Glucose measurement: confounding issues in setting targets for inpatient management. Diabetes Care 30: 403–409CrossRefPubMedGoogle Scholar
  36. 36.
    Suh SW, Gum ET, Hamby AM, Chan PH, Swanson RA (2007) Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. J Clin Invest 117: 910–918CrossRefPubMedGoogle Scholar
  37. 37.
    Rossetti P, Porcellati F, Fanelli CG, Perriello G, Torlone E, Bolli GB (2008) Superiority of insu-lin analogues versus human insulin in the treatment of diabetes mellitus. Arch Physiol Biochem 114: 3–10CrossRefPubMedGoogle Scholar
  38. 38.
    Vriesendorp TM, van Santen S, DeVries JH, et al (2006) Predisposing factors for hypoglycemia in the intensive care unit. Crit Care Med 34: 96–101CrossRefPubMedGoogle Scholar
  39. 39.
    Pieracci F, Hydo L, Eachempati S, Pomp A, Shou J, Barie PS (2008) Higher body mass index predicts need for insulin but not hyperglycemia, nosocomial infection, or death in critically ill surgical patients. Surg Infect (Larchmt) 9: 121–130CrossRefGoogle Scholar
  40. 40.
    Rusavy Z, Sramek V, Lacigova S, Novak I, Tesinsky P, Macdonald IA (2004) Influence of insulin on glucose metabolism and energy expenditure in septic patients. Crit Care 8:R213–R220CrossRefPubMedGoogle Scholar
  41. 41.
    Wiener RS, Wiener DC, Larson RJ (2008) Benefits and risks of tight glucose control in critically ill adults: A meta-analysis. JAMA 300: 933–944CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • N. A. Ali
    • 1
  • J. S. Krinsley
    • 2
  • J.-C. Preiser
    • 3
  1. 1.Division of Pulmonary, Allergy, Critical Care, and Sleep MedicineDepartment of Internal MedicineColumbusUSA
  2. 2.Department of Critical Care Stamford HospitalColumbia University College of Physicians and SurgeonsStamfordUSA
  3. 3.Department of Intensive CareCentre Hospitalier Universitaire de LiègeLiège 1Belgium

Personalised recommendations