Muscle protein catabolism after severe burn

Effects of IGF-1/IGFBP-3 treatment

David Herndon, Peter I. Ramzy, Meelie A. DebRoy, Ming Zheng, Arny A. Ferrando, David L. Chinkes, Juan P. Barret, Robert R. Wolfe, Steven Wolf

Research output: Contribution to journalArticle

138 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)713-722
Number of pages10
JournalAnnals of Surgery
Volume229
Issue number5
DOIs
StatePublished - May 1999

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Insulin-Like Growth Factor Binding Protein 3
Muscle Proteins
Somatomedins
Therapeutics
Leg
Anabolic Agents
Glucose
Muscles
Proteins
Nutritional Support
Burns
Growth Hormone
Carrier Proteins
Skeletal Muscle
Insulin

ASJC Scopus subject areas

  • Surgery

Cite this

Herndon, D., Ramzy, P. I., DebRoy, M. A., Zheng, M., Ferrando, A. A., Chinkes, D. L., ... Wolf, S. (1999). Muscle protein catabolism after severe burn: Effects of IGF-1/IGFBP-3 treatment. Annals of Surgery, 229(5), 713-722. https://doi.org/10.1097/00000658-199905000-00014

Muscle protein catabolism after severe burn : Effects of IGF-1/IGFBP-3 treatment. / Herndon, David; Ramzy, Peter I.; DebRoy, Meelie A.; Zheng, Ming; Ferrando, Arny A.; Chinkes, David L.; Barret, Juan P.; Wolfe, Robert R.; Wolf, Steven.

In: Annals of Surgery, Vol. 229, No. 5, 05.1999, p. 713-722.

Research output: Contribution to journalArticle

Herndon, D, Ramzy, PI, DebRoy, MA, Zheng, M, Ferrando, AA, Chinkes, DL, Barret, JP, Wolfe, RR & Wolf, S 1999, 'Muscle protein catabolism after severe burn: Effects of IGF-1/IGFBP-3 treatment', Annals of Surgery, vol. 229, no. 5, pp. 713-722. https://doi.org/10.1097/00000658-199905000-00014
Herndon D, Ramzy PI, DebRoy MA, Zheng M, Ferrando AA, Chinkes DL et al. Muscle protein catabolism after severe burn: Effects of IGF-1/IGFBP-3 treatment. Annals of Surgery. 1999 May;229(5):713-722. https://doi.org/10.1097/00000658-199905000-00014
Herndon, David ; Ramzy, Peter I. ; DebRoy, Meelie A. ; Zheng, Ming ; Ferrando, Arny A. ; Chinkes, David L. ; Barret, Juan P. ; Wolfe, Robert R. ; Wolf, Steven. / Muscle protein catabolism after severe burn : Effects of IGF-1/IGFBP-3 treatment. In: Annals of Surgery. 1999 ; Vol. 229, No. 5. pp. 713-722.
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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.",
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AU - Ramzy, Peter I.

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AU - Zheng, Ming

AU - Ferrando, Arny A.

AU - Chinkes, David L.

AU - Barret, Juan P.

AU - Wolfe, Robert R.

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N2 - 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.

AB - 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.

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