Muscle protein catabolism after severe burn: Effects of IGF-1/IGFBP-3 treatment

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.