A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and
Insights
Pediatric Crohn disease (CD) patients show reduced postprandial glucagon-like peptide 2 (GLP-2) release and impaired nutrient absorption during active disease. These functions normalize with healing, suggesting GLP-2 therapy potential.
Area of Science:
- Gastroenterology
- Pediatric Medicine
- Endocrinology
Background:
- The role of glucagon-like peptide 2 (GLP-2) in intestinal inflammation is not fully understood.
- GLP-2 supports mucosal growth, reduces intestinal permeability, and has anti-inflammatory effects.
- Physiological GLP-2 release is stimulated by nutrient intake.
Purpose of the Study:
- To investigate the hypothesis that ileal Crohn disease (CD) impacts GLP-2 release in pediatric patients.
- To assess the relationship between GLP-2 levels, nutrient absorption, and intestinal permeability in active CD versus remission.
Main Methods:
- Pediatric patients with active CD (disease activity index >150) and healthy controls were studied.
- Fasting and postprandial GLP-2 levels were measured.
- Intestinal permeability and glucose absorption were assessed using oral lactulose/mannitol and 3-O-methyl-glucose tests.
Main Results:
- Active CD patients had stable fasting GLP-2 but reduced postprandial GLP-2 levels.
- Reduced glucose absorption and increased intestinal permeability (lactulose/mannitol ratio) were observed in active CD.
- These parameters normalized upon disease remission.
Conclusions:
- Acute ileal Crohn disease in children is associated with decreased postprandial GLP-2 release, impaired glucose absorption, and increased intestinal permeability.
- Disease remission leads to the normalization of GLP-2 release and mucosal function, likely due to increased mucosal surface area.
- Findings suggest potential therapeutic roles for GLP-2 and specific feeding strategies in managing CD.
Unlabelled:
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.
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