Objective To determine the effects of recombinant human insulin-like growth
factor-1 (IGF-I) 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 hyper
metabolic response characterized by hyperdynamic circulation and severe mus
cle catabolism and wasting. Previous studies showed that nutritional suppor
t and pharmacologic intervention with anabolic agents such as growth hormon
e and insulin abrogated muscle wasting and improved net protein synthesis i
n the severely burned. The use of these agents, however, has several advers
e 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 bef
ore and after treatment with 0.5, 1, 2, or 4 mg/kg/day IGF-1/IGFBP-3 to det
ermine net balance of protein across the leg, muscle protein fractional syn
thetic rates, and glucose metabolism. Another group was studied in a simila
r 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-5 increased serum IGF-1, which di
d 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 prote
in fractional synthetic rates. This effect was more pronounced in catabolic
children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or ch
ange substrate utilization.
Conclusions IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolis
m in catabolic burned children with negligible clinical side effects.