title: The effect of insulin infusion upon protein metabolism in neonates on extracorporeal life support.
abstract: OBJECTIVE
  Critically ill neonates on extracorporeal life support (ECLS) demonstrate elevated rates of protein breakdown that, in turn, are associated with increased morbidity and mortality. This study sought to determine if the administration of the anabolic hormone insulin improved net protein balance in neonates on ECLS.
  
  
  METHODS
  Twelve parenterally fed neonates, on ECLS, were enrolled in a randomized, prospective, crossover trial. Subjects were administered a hyperinsulinemic euglycemic clamp and a control saline infusion. Protein metabolism was quantified using ring-D5-phenylyalanine and ring-D2-tyrosine stable isotopic infusions. Statistical comparisons were made by paired sample t tests (significance at P < 0.05).
  
  
  RESULTS
  Serum insulin concentration increased 20-fold during insulin infusion compared with saline infusion control (P < 0.0001). Protein breakdown was significantly decreased during insulin infusion compared with controls (7.98 +/- 1.82 vs. 6.89 +/- 1.03 g/kg per day; P < 0.05). Serum amino acid concentrations were significantly decreased by insulin infusion (28,450 +/- 9270 vs. 20,830 +/- 8110 micromol/L; P < 0.02). Insulin administration tended to decrease protein synthesis (9.58 +/- 2.10 g/kg per day vs. 8.60 +/- 1.20; P = 0.05). For the whole cohort, insulin only slightly improved net protein balance (protein synthesis minus protein breakdown) (1.60 +/- 0.80 vs. 1.71 +/- 0.89 g/kg per day; P = 0.08). In neonates receiving > or =2 g/kg per day of dietary amino acids insulin significantly improved net protein balance (2.17 +/- 0.34 vs. 2.40 +/- 0.26 g/kg per day; P < 0.01).
  
  
  CONCLUSIONS
  Insulin effectively decreases protein breakdown in critically ill neonates on ECLS. However, this is associated with a significant reduction in plasma amino acids and a trend toward decreased protein synthesis. Insulin administration significantly improves net protein balance only in those ECLS neonates in whom adequate dietary protein is provided.
authors.affiliation: Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael S D
authors.initials: MS
authors.lastname: Agus
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Javid
authors.forename: Hannah G
authors.initials: HG
authors.lastname: Piper
authors.forename: David
authors.initials: D
authors.lastname: Wypij
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Duggan
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Tom
authors.initials: T
authors.lastname: Jaksic
mesh_terms: D018592:Cross-Over Studies; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood*; D007332:Insulin Infusion Systems; D008297:Male; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism*
chemical_list: D007328:Insulin; D011506:Proteins