title: Clinical review: Intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target?
abstract: BACKGROUND
  Hyper- and hypoglycemia are associated with increased mortality of critically ill patients, but whether this association is causal remains unclear. Early randomized-controlled studies compared insulin infusion targeting "age-normal" blood glucose levels, labeled intensive insulin therapy, with an approach that considered hyperglycemia as a beneficial adaptation. These studies found benefits with maintaining normoglycemia. A recent large multicenter study, NICE-SUGAR, compared a similar age-normal with an intermediate glucose target and found the intermediate target superior. These results require explanation.
  
  
  METHODS
  All published randomized controlled studies on glucose control in ICU were reviewed. The methodological differences between the repeat studies, most specifically NICE-SUGAR, and the original proof-of-concept studies, were systematically analyzed.
  
  
  RESULTS
  There were important methodological differences, possibly explaining different outcomes. These comprised different target ranges for blood glucose in control and intervention groups, different routes for insulin administration and types of infusion-pumps, different sampling sites, and different accuracies of glucometers, as well as different nutritional strategies and varying levels of expertise.
  
  
  CONCLUSIONS
  These differences do not permit confident recommendations for a single optimal glucose target in variable ICU settings. Respecting the "primum non nocere" principle, it appears safe not to embark on targeting age-normal levels in ICUs that are not equipped to accurately and frequently measure blood glucose and have not acquired extensive experience with iv insulin administration using a customized guideline. A simple overall fall-back position could be to maintain blood glucose levels as close to normal as possible without evoking unacceptable fluctuations, hypoglycemia, and hypokalemia.
authors.affiliation: Laboratory and Department of Intensive Care Medicine, Catholic University of Leuven (K. U. Leuven), Herestraat 49, B-3000 Leuven, Belgium. greet.vandenberghe@med.kuleuven.be
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
authors.forename: Miet
authors.initials: M
authors.lastname: Schetz
authors.forename: Dirk
authors.initials: D
authors.lastname: Vlasselaers
authors.forename: Greet
authors.initials: G
authors.lastname: Hermans
authors.forename: Alexander
authors.initials: A
authors.lastname: Wilmer
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D016638:Critical Illness; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007362:Intensive Care Units; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose; D007328:Insulin