Exogenous insulin reduces proteolysis and protein synthesis in extremely low birth weight infants.

OBJECTIVE: To determine the effect of a continuous insulin infusion on protein and glucose metabolism in extremely low birth weight (ELBW) infants. STUDY
DESIGN: We measured the rate of appearance (Ra) of the essential amino acids leucine and phenylalanine (reflecting proteolysis), utilization of phenylalanine for protein synthesis, and glucose Ra using stable isotope tracers during a basal infusion of glucose (6 mg/kg/min) and in response to a continuous infusion of insulin (0.05 U/kg/hr) by means of the euglycemic hyperinsulinemic clamp technique. Four clinically stable, euglycemic ELBW infants (26 +/- 0 weeks' gestation, 894 +/- 44 gm birth weight, 2.8 +/- 0.8 days of age) were studied.
RESULTS: In response to a greater than tenfold increase in insulin concentration (from 7 +/- 2 to 79 +/- 13 microU/ml), there was a 20% decrease in leucine Ra (Basal: 272 +/- 27 mumol/kg/hr; Insulin: 226 +/- 29 mumol/kg/hr; p < 0.01) and in phenylalanine Ra (Basal: 91 +/- 5 mumol/kg/hr; Insulin: 72 +/- 2 mumol/kg/hr; p < 0.05). Use of phenylalanine for protein synthesis also decreased by a similar magnitude (Basal: 77 +/- 4 mumol/kg/hr; Insulin: 62 +/- 1 mumol/kg/hr; p < 0.05). Glucose utilization doubled (from 8 +/- 0.9 to 15.7 +/- 1.1 mg/kg/min; p = 0.0003) and plasma lactate concentrations tripled (from 2.1 +/- 0.5 to 5.7 +/- 1.0 mmol/L; p < 0.05) during the insulin infusion.
CONCLUSIONS: During an infusion of glucose alone, pharmacologic concentrations of insulin in ELBW infants produced no net protein anabolic effect. Furthermore, euglycemic hyperinsulinemia was accompanied by development of significant metabolic acidosis.