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

Abstract

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.

Figure 1. Experimental design of stable isotype design infusion protocol. The upper line depicts the study time periods. The lower line shows the stable isotopic infusion study design.

Figure 2. Serum IGF-1 levels with IGF-1/IGFBP-3 infusion. Circles represent means; bars represent SEM. Significant differences from control, p < 0.05.

Figure 3. Phenylalanine net balance across the leg in noncatabolic and catabolic children as determined by net phenylalanine balance during the control period. Symbols represent individual patients. Significant differences were found in the change with treatment in the catabolic group only (p < 0.05).

Figure 4. Glucose uptake across the leg in severely burned children after IGF-1/IGFBP-3 treatment. Circles represent means; bars represent SEM. No significant differences could be shown between control and treatment.