Intensive Care Medicine

, Volume 42, Issue 9, pp 1478–1481 | Cite as

Blood glucose control in the ICU: don’t throw out the baby with the bathwater!

  • Jan Gunst
  • Greet Van den BergheEmail author
What's New in Intensive Care

In this issue of Intensive Care Medicine, Dr. Paul Marik presents his personal critical viewpoint on the use of tight glycemic control (TGC) in the intensive care unit (ICU) [1]. He recommends to abandon glycemic control altogether for critically ill patients, based upon a risk of harm that, in his interpretation, would outweigh any possible benefit. At first sight, Dr. Marik’s arguments appear reasonable. However, in our opinion, his argumentation was built on a biased/incomplete analysis of the evidence. We here present another (in our view more balanced) analysis. We argue that Dr. Marik is inadvertently recommending clinicians to throw out the baby with the bathwater.

Dr. Marik starts his case with an evolutionary perspective, stating that humans and animals alike reveal hyperglycemia when exposed to stress, and thus that this must be beneficial. We do not agree. Fasted young and lean human patients, as well as laboratory mice, in the absence of forced artificial nutrition and...


Intensive Care Unit Hyperglycemia Hypoglycemia Glycemic Variability Tight Glycemic 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.



GVdB receives research grants from the Research Foundation—Flanders, from the Methusalem Program funded by the Flemish Government (METH/14/06), and from the European Research Council under the European Union’s Seventh Framework Program (FP7/2013-2018 ERC Advanced Grant Agreement n° 321670).

Compliance with ethical standards

Conflicts of interest

The authors declare to have no conflict of interest.


  1. 1.
    Marik PE (2016) Glycemic control in acutely ill patients: low evidence of benefit, high evidence of harm! Intensive Care Med. doi: 10.1007/s00134-016-4299-2 Google Scholar
  2. 2.
    Gunst J, Van den Berghe G (2010) Blood glucose control in the intensive care unit: benefits and risks. Semin Dial 23:157–162. doi: 10.1111/j.1525-139X.2010.00702.x CrossRefPubMedGoogle Scholar
  3. 3.
    Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367. doi: 10.1056/NEJMoa011300 CrossRefGoogle Scholar
  4. 4.
    Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354:449–461. doi: 10.1056/NEJMoa052521 CrossRefPubMedGoogle Scholar
  5. 5.
    Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, Mesotten D, Casaer MP, Meyfroidt G, Ingels C, Muller J, Van Cromphaut S, Schetz M, Van den Berghe G (2009) Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet 373:547–556. doi: 10.1016/S0140-6736(09)60044-1 CrossRefPubMedGoogle Scholar
  6. 6.
    NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297. doi: 10.1056/NEJMoa0810625 CrossRefGoogle Scholar
  7. 7.
    Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G (2011) Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365:506–517. doi: 10.1056/NEJMoa1102662 CrossRefPubMedGoogle Scholar
  8. 8.
    Casaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G (2013) Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med 187:247–255. doi: 10.1164/rccm.201206-0999OC CrossRefPubMedGoogle Scholar
  9. 9.
    Derde S, Vanhorebeek I, Güiza F, Derese I, Gunst J, Fahrenkrog B, Martinet W, Vervenne H, Ververs EJ, Larsson L, Van den Berghe G (2012) Early parenteral nutrition evokes a phenotype of autophagy deficiency in liver and skeletal muscle of critically ill rabbits. Endocrinology 153:2267–2276. doi: 10.1210/en.2011-2068 CrossRefPubMedGoogle Scholar
  10. 10.
    Ellger B, Debaveye Y, Vanhorebeek I, Langouche L, Giulietti A, Van Etten E, Herijgers P, Mathieu C, Van den Berghe G (2006) Survival benefits of intensive insulin therapy in critical illness: impact of maintaining normoglycemia versus glycemia-independent actions of insulin. Diabetes 55:1096–1105. doi: 10.2337/diabetes.55.04.06.db05-1434 CrossRefPubMedGoogle Scholar
  11. 11.
    Derde S, Vanhorebeek I, Ververs EJ, Vanhees I, Darras VM, Van Herck E, Larsson L, Van den Berghe G (2010) Increasing intravenous glucose load in the presence of normoglycemia: effect on outcome and metabolism in critically ill rabbits. Crit Care Med 38:602–611. doi: 10.1097/CCM.0b013e3181c03f65 CrossRefPubMedGoogle Scholar
  12. 12.
    Sonneville R, den Hertog HM, Derde S, Güiza F, Derese I, Van den Berghe G, Vanhorebeek I (2013) Increasing glucose load while maintaining normoglycemia does not evoke neuronal damage in prolonged critically ill rabbits. Clin Nutr 32:1077–1080. doi: 10.1016/j.clnu.2013.01.003 CrossRefPubMedGoogle Scholar
  13. 13.
    Vanhorebeek I, Ellger B, De Vos R, Boussemaere M, Debaveye Y, Vander Perre S, Rabbani N, Thornalley PJ, Van den Berghe G (2009) Tissue-specific glucose toxicity induces mitochondrial damage in a burn injury model of critical illness. Crit Care Med 37:1355–1364. doi: 10.1097/CCM.0b013e31819cec17 CrossRefPubMedGoogle Scholar
  14. 14.
    Vanhorebeek I, Gunst J, Ellger B, Boussemaere M, Lerut E, Debaveye Y, Rabbani N, Thornalley PJ, Schetz M, Van den Berghe G (2009) Hyperglycemic kidney damage in an animal model of prolonged critical illness. Kidney Int 76:512–520. doi: 10.1038/ki.2009.217 CrossRefPubMedGoogle Scholar
  15. 15.
    Sonneville R, den Hertog HM, Guïza F, Gunst J, Derese I, Wouters PJ, Brouland JP, Polito A, Gray F, Chrétien F, Charlier P, Annane D,  Sharshar T, Van den Berghe G, Vanhorebeek I (2012) Impact of hyperglycemia on neuropathological alterations during critical illness. J Clin Endocrinol Metab 97:2113–2123. doi: 10.1210/jc.2011-2971 CrossRefPubMedGoogle Scholar
  16. 16.
    Van Herpe T, Mesotten D, Wouters PJ, Herbots J, Voets E, Buyens J, De Moor B, Van den Berghe G (2013) LOGIC-insulin algorithm-guided versus nurse-directed blood glucose control during critical illness: the LOGIC-1 single-center, randomized, controlled clinical trial. Diabetes Care 36:188–194. doi: 10.2337/dc12-0584 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    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 117:910–918. doi: 10.1172/JCI30077 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Mesotten D, Gielen M, Sterken C, Claessens K, Hermans G, Vlasselaers D, Lemiere J, Lagae L, Gewillig M, Eyskens B, Vanhorebeek I, Wouters PJ, Van den Berghe G (2012) Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial. JAMA 308:1641–1650. doi: 10.1001/jama.2012.12424 CrossRefPubMedGoogle Scholar
  19. 19.
    Vanhorebeek I, De Vos R, Mesotten D, Wouters PJ, De Wolf-Peeters C, Van den Berghe G (2005) Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients. Lancet 365:53–59. doi: 10.1016/S0140-6736(04)17665-4 CrossRefPubMedGoogle Scholar
  20. 20.
    Langouche L, Vanhorebeek I, Vlasselaers D, Vander Perre S, Wouters PJ, Skogstrand K, Hansen TK, Van den Berghe G (2005) Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest 115:2277–2286. doi: 10.1172/JCI25385 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ellger B, Langouche L, Richir M, Debaveye Y, Vanhorebeek I, Teerlink T, Van Leeuwen PA, Van den Berghe G (2008) Modulation of regional nitric oxide metabolism: blood glucose control or insulin? Intensive Care Med 34:1525–1533. doi: 10.1007/s00134-008-1118-4 CrossRefPubMedGoogle Scholar
  22. 22.
    Mesotten D, Swinnen JV, Vanderhoydonc F, Wouters PJ, Van den Berghe G (2004) Contribution of circulating lipids to the improved outcome of critical illness by glycemic control with intensive insulin therapy. J Clin Endocrinol Metab 89:219–226. doi: 10.1210/jc.2003-030760 CrossRefPubMedGoogle Scholar
  23. 23.
    Vlasselaers D, Mesotten D, Langouche L, Vanhorebeek I, van den Heuvel I, Milants I, Wouters P, Wouters P, Meyns B, Bjerre M, Hansen TK, Van den Berghe G (2010) Tight glycemic control protects the myocardium and reduces inflammation in neonatal heart surgery. Ann Thorac Surg 90:22–29. doi: 10.1016/j.athoracsur.2010.03.093 CrossRefPubMedGoogle Scholar
  24. 24.
    Weekers F, Giulietti AP, Michalaki M, Coopmans W, Van Herck E, Mathieu C, Van den Berghe G (2003) Metabolic, endocrine, and immune effects of stress hyperglycemia in a rabbit model of prolonged critical illness. Endocrinology 144:5329–5338. doi: 10.1210/en.2003-0697 CrossRefPubMedGoogle Scholar
  25. 25.
    Ingels C, Moller HJ, Hansen TK, Wouters PJ, Vanhorebeek I, Van den Berghe G (2013) Circulating levels of the shed scavenger receptor sCD163 and association with outcome of critically ill patients. J Clin Immunol 33:619–629. doi: 10.1007/s10875-012-9830-9 CrossRefPubMedGoogle Scholar
  26. 26.
    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 64:1348–1353. doi: 10.1212/01.WNL.0000158442.08857.FC CrossRefPubMedGoogle Scholar
  27. 27.
    Hermans G, Wilmer A, Meersseman W, Milants I, Wouters PJ, Bobbaers H, Bruyninckx F, Van den Berghe G (2007) Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care Med 175:480–489. doi: 10.1164/rccm.200605-665OC CrossRefPubMedGoogle Scholar
  28. 28.
    Schetz M, Vanhorebeek I, Wouters PJ, Wilmer A, Van den Berghe G (2008) Tight blood glucose control is renoprotective in critically ill patients. J Am Soc Nephrol 19:571–578. doi: 10.1681/ASN.2006101091 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Mesotten D, Wauters J, Van den Berghe G, Wouters PJ, Milants I, Wilmer A (2009) The effect of strict blood glucose control on biliary sludge and cholestasis in critically ill patients. J Clin Endocrinol Metab 94:2345–2352. doi: 10.1210/jc.2008-2579 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2016

Authors and Affiliations

  1. 1.Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular MedicineKU LeuvenLouvainBelgium

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