title: Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children.
abstract: To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children.
  
  
  
  Open-label randomized mechanistic study.
  
  
  
  Two-center, tertiary PICU study.
  
  
  
  Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures.
  
  
  
  Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management.
  
  
  
  Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1β were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged.
  
  
  
  Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.
authors.affiliation: 1Paediatric Intensive Care Unit, Department of Paediatrics, Addenbrookes Hospital, Cambridge, United Kingdom.2Department of Paediatrics, Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil.3Departments of Neurology and Anesthesia, Boston Children's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Ricardo G
authors.initials: RG
authors.lastname: Branco
authors.forename: Pedro Celiny R
authors.initials: PC
authors.lastname: Garcia
authors.forename: Jefferson P
authors.initials: JP
authors.lastname: Piva
authors.forename: Geniara S
authors.initials: GS
authors.lastname: Conrado
authors.forename: Felipe
authors.initials: F
authors.lastname: Cabral
authors.forename: Cecilia
authors.initials: C
authors.lastname: Korb
authors.forename: Humberto
authors.initials: H
authors.lastname: Fiori
authors.forename: Matteo
authors.initials: M
authors.lastname: Baldisserotto
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tasker
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D016207:Cytokines / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D010865:Pilot Projects; D052683:Somatotrophs / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007004:Hypoglycemic Agents; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I