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Exogenous insulin reduces proteolysis and protein synthesis in extremely low birth weight infants
B B Poindexter1, C A Karn, S C Denne
1Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202-5210, USA.
Insights
Continuous insulin infusion in extremely low birth weight (ELBW) infants did not promote protein synthesis and led to metabolic acidosis. This study highlights potential risks of insulin therapy in vulnerable newborns.
Area of Science:
- Neonatalogy
- Pediatric Endocrinology
- Metabolic Research
Background:
- Extremely low birth weight (ELBW) infants face unique metabolic challenges.
- Understanding substrate metabolism is crucial for optimizing care in premature neonates.
- Insulin's role in neonatal metabolism, particularly in ELBW infants, requires further elucidation.
Purpose of the Study:
- To investigate the impact of continuous insulin infusion on protein and glucose metabolism in ELBW infants.
- To assess the effects of pharmacologic insulin concentrations on amino acid and glucose kinetics.
- To evaluate the safety and efficacy of insulin therapy in this fragile population.
Main Methods:
- Utilized stable isotope tracers to measure the rate of appearance (Ra) of essential amino acids (leucine, phenylalanine) and glucose.
- Employed the euglycemic hyperinsulinemic clamp technique to achieve controlled insulin levels.
- Studied four clinically stable ELBW infants using precise metabolic measurements.
Main Results:
- Insulin infusion significantly decreased leucine and phenylalanine Ra, indicating reduced proteolysis.
- Phenylalanine utilization for protein synthesis also decreased, suggesting an anti-anabolic effect.
- Glucose utilization doubled, while plasma lactate concentrations tripled, indicating altered glucose handling and potential for acidosis.
Conclusions:
- Pharmacologic insulin concentrations in ELBW infants receiving glucose infusion did not result in a net protein anabolic effect.
- Euglycemic hyperinsulinemia was associated with the development of significant metabolic acidosis.
- These findings suggest caution when using insulin therapy in ELBW infants due to potential adverse metabolic consequences.
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.