Growth hormone enhances fat-free mass and glutamine availability in patients with short-bowel syndrome: an ancillary double-blind, randomized crossover study

Am J Clin Nutr. 2014 Sep;100(3):850-8. doi: 10.3945/ajcn.113.071845. Epub 2014 Jul 30.

Abstract

Background: Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial.

Objective: We explored effects of rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action.

Design: Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg⁻¹ · d⁻¹) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment.

Results: rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states.

Conclusions: In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Composition / drug effects
  • Cohort Studies
  • Combined Modality Therapy
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Glutamine / biosynthesis*
  • Glutamine / blood
  • Glutamine / metabolism
  • Human Growth Hormone / genetics
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Hyperphagia / etiology
  • Insulin Resistance
  • Intestinal Absorption / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / physiopathology
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Intestine, Small / physiopathology
  • Male
  • Middle Aged
  • Parenteral Nutrition, Home
  • Postprandial Period
  • Protein Biosynthesis / drug effects
  • Proteolysis / drug effects
  • Recombinant Proteins / therapeutic use
  • Severity of Illness Index
  • Short Bowel Syndrome / drug therapy*
  • Short Bowel Syndrome / metabolism
  • Short Bowel Syndrome / physiopathology
  • Short Bowel Syndrome / therapy
  • Weight Gain / drug effects

Substances

  • Gastrointestinal Agents
  • Recombinant Proteins
  • Glutamine
  • Human Growth Hormone