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Muscle protein catabolism after severe burn: effects of IGF-1/IGFBP-3 treatment
D N Herndon1, P I Ramzy, M A DebRoy
1Department of Surgery, University of Texas Medical Branch and the Shriners Burns Hospital, Galveston 77550, USA.
Insights
Recombinant human insulin-like growth factor-1 (IGF-1) complexed with IGFBP-3 effectively reduces muscle wasting in severely burned children. This treatment improves protein balance and muscle synthesis with minimal side effects.
Area of Science:
- Biochemistry
- Metabolic Research
- Pediatric Critical Care
Background:
- Severe burns trigger a hypermetabolic state, leading to muscle catabolism and wasting.
- Previous anabolic interventions (growth hormone, insulin) showed efficacy but carried adverse effects.
- Recombinant human insulin-like growth factor-1 (IGF-1) complexed with IGFBP-3 presents a novel therapeutic option.
Purpose of the Study:
- To evaluate the impact of IGF-1/IGFBP-3 on skeletal muscle metabolism in pediatric burn patients.
- To assess effects on protein balance, muscle protein synthesis, and glucose metabolism.
Main Methods:
- Prospective study of 29 severely burned children receiving varying doses of IGF-1/IGFBP-3.
- Measurements included leg protein balance, muscle protein fractional synthetic rates, and glucose metabolism.
- A control group was monitored without IGF-1/IGFBP-3 treatment.
Main Results:
- IGF-1/IGFBP-3 treatment (1-4 mg/kg/day) improved net protein balance and increased muscle protein synthesis rates.
- The anabolic effect was more significant in children who were initially catabolic.
- No significant changes were observed in leg glucose uptake or substrate utilization.
Conclusions:
- IGF-1/IGFBP-3 therapy effectively attenuates muscle catabolism in severely burned children.
- Doses ranging from 1 to 4 mg/kg/day demonstrated positive effects on protein metabolism.
- The treatment showed negligible clinical side effects, suggesting a favorable safety profile.
Objective:
To determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children.
Summary Background Data:
Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study.
Methods:
Twenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls.
Results:
Seventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization.
Conclusions:
IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.