Growth Hormone, Glutamine, and a Modified Diet Enhance Nutrient Absorption in Patients With Severe Short Bowel Syndrome

Byrne, Theresa A.; Morrissey, Thomas B.; Nattakom, Thomas V.; Ziegler, Thomas R.; Wilmore, Douglas W.

doi:10.1177/0148607195019004296

Cited by 246 publications

(105 citation statements)

References 35 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…In another open-labeled study, 32 the combination of growth hormone, glutamine, and high-carbohydrate diet improved energy absorption approximately 590 KJ/day in 8 short-bowel patients who all had preserved colonic continuity, which possibly was a result of the increase in carbohydrate intake known to increase energy absorption in patients with a colon. 39 In comparison, we found that GLP-2 increased absorption 440 kJ/day on a fixed diet.…”

Section: Discussionmentioning

confidence: 97%

“…27 Therefore, the search for factors to enhance small bowel adaptation and to increase the assimilation of macronutrients and absorption of water and electrolytes, thereby decreasing the need for parenteral nutrition, has been intensive. The concept of "bowel rehabilitation" was introduced by Byrne et al 31,32 with the introduction of growth hormone and glutamine in the treatment of short-bowel patients. However, their encouraging results have been disputed in later randomized, double-blinded studies.…”

Section: Discussionmentioning

confidence: 99%

“…32 The 2 blinded studies using growth hormone and glutamine resulted in symptoms of fluid retention known to occur during treatment with growth hormone, but a beneficial effect on intestinal absorption of wet weight was not documented. 33,34 The observed effects on body weight and body composition resembled effects obtained in studies using growth hormone, 40,41 but in contrast to findings after treatment with growth hormone, no clinical signs of edema occurred during GLP-2 treatment.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

et al. 2001

View full text Add to dashboard Cite

Background & Aims: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. Methods: Balance studies were performed before and after treatment with GLP-2, 400 g subcutaneously twice a day for 35 days, in 8 patients (4 -17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. Results: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% ؎ 4.0% (mean ؎ SD) from 49.9% to 53.4% (P ‫؍‬ 0.04), wet weight 11% ؎ 12% from 25% to 36% (P ‫؍‬ 0.04), and nitrogen 4.7% ؎ 5.4% from 47.4% to 52.1% (P ‫؍‬ 0.04). Body weight increased 1.2 ؎ 1.0 kg (P ‫؍‬ 0.01), lean body mass increased 2.9 ؎ 1.9 kg (P ‫؍‬ 0.004), fat mass decreased 1.8 ؎ 1.3 kg (P ‫؍‬ 0.007), and 24-hour urine creatinine excretion increased (P ‫؍‬ 0.02). The time to 50% gastric emptying of solids increased 30 ؎ 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. Conclusions: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

et al. 2001

View full text Add to dashboard Cite

show abstract

“…70 At 2 years, 57% of patients were independent of PN. 70 This is contrary to the results of Scolapio et al , who repeated a randomized, 6-week, double-blind, placebo-controlled, crossover study with similar treatment conditions to those of Bryne et al 68,69 and Weiming et al 70 but who reported only modest improvements in electrolyte absorption and no improvement in small bowel morphology, stool losses, or macronutrient absorption. 5,56 In pediatric case studies long-term low-dose rhGH treatment combined with glutamine supplementation and HCLF diet has 71 Two further case studies have shown increased tolerance to enteral feeding, and decreased stool output following rhGH treatment.…”

Section: Clinical Experiencementioning

confidence: 76%

“…68,69 At 1 year following the study 40% of patients treated with rhGH remained PN-independent. 69 Similarly, 3 weeks of treatment with rhGH, glutamine, and HCLF diet was associated with significant improvements in intestinal absorptive capacity and plasma levels of proteins in adult PN-dependent SBS patients.…”

Section: Clinical Experiencementioning

confidence: 99%

New growth factor therapies aimed at improving intestinal adaptation in short bowel syndrome

Pereira¹,

Bines²

2006

J of Gastro and Hepatol

View full text Add to dashboard Cite

Short bowel syndrome (SBS) is used to describe a condition of malabsorption and malnutrition resulting from the loss of absorptive area following massive small bowel resection. The key to improved clinical outcome after massive small bowel resection is the ability of the residual bowel to adapt. Although still in experimental stages, a major goal in the management of SBS may be the augmented use of growth factors to promote increased adaptation. A number of growth factors have been implicated in promoting the adaptation process. The best-described growth factors are reviewed: glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF), and growth hormone (GH). This article reviews the ability of recombinant GLP-2, EGF and GH to modulate structural and functional aspects of intestinal adaptation following small bowel resection. Although these growth factors have shown promise, small sample size, inconsistent measurement parameters and uncontrolled study designs have hampered the acquisition of strong data advocating the use of growth factor treatment for SBS. Multicenter trials using well-defined outcome measures to assess clinical efficacy are needed to direct the clinical indications, timing and duration of therapy and assess potential risks associated with growth factor therapies.

show abstract

Glucagonlike Peptide 2 Analogue Teduglutide

Chaturvedi

Basson

2013

JAMA Surg

View full text Add to dashboard Cite

IMPORTANCE Short bowel syndrome occurs when a shortened intestine cannot absorb sufficient nutrients or fluids. Teduglutide is a recombinant analogue of human glucagonlike peptide 2 that reduces dependence on parenteral nutrition in patients with short bowel syndrome by promoting enterocytic proliferation, increasing the absorptive surface area. However, enterocyte function depends not only on the number of cells that are present but also on differentiated features that facilitate nutrient absorption and digestion. OBJECTIVE To test the hypothesis that teduglutide impairs human intestinal epithelial differentiation. DESIGN AND SETTING We investigated the effects of teduglutide in the modulation of proliferation and differentiation in human Caco-2 intestinal epithelial cells at a basic science laboratory. This was an in vitro study using Caco-2 cells, a human-derived intestinal epithelial cell line commonly used to model enterocytic biology. EXPOSURE Cells were exposed to teduglutide or vehicle control. MAINOUTCOMESAND MEASURES We analyzed the cell cycle by bromodeoxyuridine incorporation or propidium iodide staining and flow cytometry and measured cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We used quantitative reverse transcription–polymerase chain reaction to assay the expression of the enterocytic differentiation markers villin, sucrase-isomaltase, glucose transporter 2 (GLUT2), and dipeptidyl peptidase 4 (DPP-4), as well as that of the putative differentiation signals schlafen 12 (SLFN12) and caudal-related homeobox intestine-specific transcription factor (Cdx2). Villin promoter activity was measured by a luciferase-based assay. RESULTS The MTS assay demonstrated that teduglutide increased cell numbers by a mean (SD) of 10% (2%) over untreated controls at a maximal 500nM (n = 6, P < .05). Teduglutide increased bromodeoxyuridine-positive cells vs untreated controls by a mean (SD) of 19.4% (2.3%) vs 12.0% (0.8%) (n = 6, P < .05) and increased the S-phase fraction by flow cytometric analysis. Teduglutide reduced the mean (SD) expression of villin by 29% (6%), Cdx2 by 31% (10%), DPP-4 by 15% (6%), GLUT2 by 40% (11%), SLFN12 by 61% (14%), and sucrase-isomaltase by 28% (8%) (n = 6, P < .05 for all). CONCLUSIONS AND RELEVANCE Teduglutide increased Caco-2 proliferation but tended to inhibit intestinal epithelial differentiation. The effects of mitogenic stimulation with teduglutide in patients with short bowel syndrome might be greater if the more numerous teduglutide-treated cells could be stimulated toward a more fully differentiated phenotype.

show abstract

Growth Hormone, Glutamine, and a Modified Diet Enhance Nutrient Absorption in Patients With Severe Short Bowel Syndrome

Cited by 246 publications

References 35 publications

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

New growth factor therapies aimed at improving intestinal adaptation in short bowel syndrome

Glucagonlike Peptide 2 Analogue Teduglutide

Contact Info

Product

Resources

About