title: Effect of intensive insulin therapy on the somatotropic axis of critically ill children.
abstract: BACKGROUND
  Intensive insulin therapy (IIT) improved outcome in the adult and pediatric intensive care unit (PICU) compared with conventional insulin therapy (CIT). IIT did not increase the anabolic hormone IGF-I in critically ill adults, but feeding in critically ill children and pediatric hormonal responses may differ. Twenty-five percent of the children with IIT experienced hypoglycemia, which may have evoked counterregulatory responses.
  
  
  OBJECTIVE
  We hypothesized that IIT reactivates the somatotropic axis and anabolism in PICU patients.
  
  
  METHODS
  This was a preplanned subanalysis of a randomized controlled trial on IIT.
  
  
  METHODS
  We studied 369 patients who stayed in PICU for at least 3 d (study 1) and 126 patients in a nested case-control study (study 2).
  
  
  METHODS
  Circulating insulin, C-peptide, GH, IGF-I, bioavailable IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit were analyzed upon admission and d 3. In the nested case-control study, the somatotropic axis, cortisol, and glucagon were analyzed before and after hypoglycemia.
  
  
  RESULTS
  On d 3, C-peptide was more than 10-fold lower (P < 0.0001) in the IIT group than in the CIT group. IIT increased circulating GH (P = 0.04) and lowered bioavailable IGF-I (P = 0.002). IIT also decreased IGFBP-3 (P = 0.0005) and acid-labile subunit (P = 0.007), while increasing IGFBP-1 (P = 0.04) and the urea/creatinine ratio, a marker of catabolism (P = 0.03). In the nested case-control study, IGFBP-1 was increased after hypoglycemia, whereas the somatotropic axis and the counterregulatory hormones cortisol and glucagon did not change.
  
  
  CONCLUSIONS
  Despite improved PICU outcome, IIT did not counteract the catabolic state of critical illness. Suppression of portal insulin may have resulted in lower bioavailable IGF-I.
authors.affiliation: Department and Laboratory of Intensive Care Medicine, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Gielen
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
authors.forename: Michael
authors.initials: M
authors.lastname: Brugts
authors.forename: Willy
authors.initials: W
authors.lastname: Coopmans
authors.forename: Erik
authors.initials: E
authors.lastname: Van Herck
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Robert
authors.initials: R
authors.lastname: Baxter
authors.forename: Steven
authors.initials: S
authors.lastname: Lamberts
authors.forename: Joop A M J L
authors.initials: JA
authors.lastname: Janssen
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D000293:Adolescent; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D005934:Glucagon / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015278:Intensive Care Units, Pediatric; D008297:Male; D011446:Prospective Studies
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D006854:Hydrocortisone