Effect of intensive insulin therapy on the somatotropic axis of critically ill children

J Clin Endocrinol Metab. 2011 Aug;96(8):2558-66. doi: 10.1210/jc.2010-3045. Epub 2011 Jun 1.

Abstract

Context: 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.

Design: This was a preplanned subanalysis of a randomized controlled trial on IIT.

Patients: 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).

Main outcome measures: 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.

Trial registration: ClinicalTrials.gov NCT00214916.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • C-Peptide / blood
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Critical Illness / therapy*
  • Female
  • Glucagon / blood
  • Human Growth Hormone / blood*
  • Humans
  • Hydrocortisone / blood
  • Hypoglycemia / chemically induced
  • Hypoglycemia / metabolism*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood
  • Infant
  • Infant, Newborn
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Insulin / blood
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Intensive Care Units, Pediatric
  • Male
  • Prospective Studies

Substances

  • C-Peptide
  • Hypoglycemic Agents
  • IGFBP1 protein, human
  • IGFBP3 protein, human
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Glucagon
  • Hydrocortisone

Associated data

  • ClinicalTrials.gov/NCT00214916