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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A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients. / Sigalet, David L; Kravarusic, Dragan; Butzner, Decker; Hartmann, Bolette; Holst, Jens Juul; Meddings, Jon.
In: Canadian Journal of Gastroenterology, Vol. 27, No. 10, 10.2013, p. 587-92.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients
AU - Sigalet, David L
AU - Kravarusic, Dragan
AU - Butzner, Decker
AU - Hartmann, Bolette
AU - Holst, Jens Juul
AU - Meddings, Jon
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - 3-O-Methylglucose
KW - Adolescent
KW - Child
KW - Crohn Disease
KW - Female
KW - Glucagon-Like Peptide 2
KW - Humans
KW - Intestinal Absorption
KW - Intestine, Small
KW - Lactulose
KW - Longitudinal Studies
KW - Male
KW - Mannitol
KW - Pilot Projects
KW - Postprandial Period
KW - Signal Transduction
M3 - Journal article
C2 - 24106731
VL - 27
SP - 587
EP - 592
JO - Canadian Journal of Gastroenterology
JF - Canadian Journal of Gastroenterology
SN - 2291-2789
IS - 10
ER -
ID: 117853262