The Effect of Insulin Infusion Upon Protein Metabolism in Neonates on Extracorporeal Life Support
Michael S.D. Agus, M.D.*, Patrick J. Javid, M.D.*, Hannah G. Piper, M.D.*, Biren P. Modi, M.D.*, Christopher Duggan, M.D.*, Daniel P. Ryan, M.D.*, Tom Jaksic, M.D. , Ph.D.*
Children's Hospital Boston, Boston, MA
Sponsored by: Robert Shamberger, M.D.
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.
After appropriate Institutional Review Board approval, 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).
Serum insulin concentration increased 20-fold during insulin infusion compared to saline infusion control (p<0.0001). Protein breakdown was significantly decreased during insulin infusion compared to controls (6.89+1.03 vs. 7.98+1.82 g/kg/day, p<0.05). Serum amino acid concentrations were significantly decreased by insulin infusion (2083+811 vs. 2845+927 µmol/dl, p<0.02). Insulin administration tended to decrease protein synthesis (8.60+1.20 vs. 9.58+2.10 g/kg/day, p=0.05). For the whole cohort insulin only slightly improved net protein balance (protein synthesis minus protein breakdown) (1.71+0.89 vs. 1.60+0.80 g/kg/day, p=0.08). In neonates receiving > 2g/kg/day of dietary amino acids insulin significantly improved net protein balance (2.40+0.26 vs. 2.17+0.34 g/kg/day, p<0.01).
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.
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