A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

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David L Sigalet, Dragan Kravarusic, Decker Butzner, Bolette Hartmann, Jens Juul Holst, Jon Meddings

 

BACKGROUND⁄/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release.

METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and postprandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose⁄mannitol (passive) were quantified during the acute and remission phases.

RESULTS: Seven patients (mean [± SD] age 15.3 ± 1.3 years) and 10 controls (10.3 ± 1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose⁄mannitol recovery; all normalized with disease remission. The change in the lactulose⁄mannitol ratio was due to both reduced lactulose and increased mannitol absorption.

CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended.

Original languageEnglish
JournalCanadian Journal of Gastroenterology
Volume27
Issue number10
Pages (from-to)587-92
Number of pages6
ISSN0835-7900
Publication statusPublished - Oct 2013

    Research areas

  • 3-O-Methylglucose, Adolescent, Child, Crohn Disease, Female, Glucagon-Like Peptide 2, Humans, Intestinal Absorption, Intestine, Small, Lactulose, Longitudinal Studies, Male, Mannitol, Pilot Projects, Postprandial Period, Signal Transduction

ID: 117853262