Is the Expression of the GLUT5 Specific Fructose Transport Protein Abnormal in Patients With Fructose Intolerance?

In this study we will investigate the expression of the fructose transport protein GLUT5 in the small intestine in patients with functional GI disoders and fructose intolerance compared to matched healthy controls.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome; Fructose Intolerance

Detailed Description

Intolerances to food are a major complaint of patients with functional gastrointestinal disorders (FGID) and even commoner in patients with inflammatory bowel disorders (IBD) (Barrett JS et al. Aliment Pharmacol Therap 2009;30:165-174). The most common forms of food intolerance are FODMAP (fermentable oligo-, di- and monosaccharide and polyol) -related, of which fructose and lactose are the best known. The prevalence of lactose and fructose intolerance in IBS patients is between 50 and 70% (Wilder-Smith CH et al. Gastroenterology 2009;136 (Suppl. 1): A324). Recent high quality studies have shown that the reduction of ingested FODMAP can lead to significant and long-term symptom improvement in patients shown to be intolerant by breath-testing. While the pathophysiology behind lactose intolerance is the reduction in small intestinal lactase availability, the mechanism in fructose intolerance and its relationship to malabsorption are unknown. One possible and so far uninvestigated mechanism is a reduction in the expression or activity of the specific fructose transporter, GLUT5, which is mainly responsible for luminal absorption of fructose. GLUT5 is mainly found in the small intestine, as well as various extra-intestinal organs. The clinical relevance of GLUT5 expression for food intolerances in humans has not been reported, but in a mouse model deletion of GLUT5 led to decreased absorption of dietary fructose and typical signs of malabsorption (Barone S et al. J Biol Chem 2009;284:5056-5066). The control of GLUT5 is dynamic and considerable upregulation together with increased absorption of fructose is evident in diabetes mellitus, while expression is decreased by inflammation and lipopolysaccharide endotoxin, an integral component of the outer membrane of all gram-negative bacteria, through the action of pro-inflammatory cytokines, such as TFN-a.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland
    • Gastoenterology Group Practice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients referred to our practice for evaluation of symptoms consistent with FGID undergoing upper GI endoscopy with biopsy and fructose breath testing as part of their usual clinical evaluation.

Description

Inclusion Criteria:

• Patients referred to our practice for evaluation of symptoms consistent with FGID undergoing upper GI endoscopy with biopsy and fructose breath testing as part of their usual clinical evaluation. Male or female patients aged between 18 and 60 years with FGID (Irritable Bowel Syndrome (IBS), Functional Dyspepsia (FD) or Functional Bloating (FB), as defined by Rome III criteria.
• Successive patients without fructose intolerance undergoing upper GI endoscopy for other reasons without inflammatory disease

Exclusion Criteria:

• Inflammatory GI disease, coeliac's disease, other relevant systemic disorders as judged by investigator, concomitant antiinflammtory treatments, absent informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
IBS patients with fructose intolerance; analysis of biopsies
Control group: no IBS or fructose intolerance; analysis of biopsies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mRNA and protein expression of Glut5	on day of endoscopy

Secondary Outcome Measures

Outcome Measure	Time Frame
mRNA and protein expression of Glut2	on day of endoscopy

Collaborators and Investigators

• Sponsor: Brain-Gut Research Group
• Investigators: Principal Investigator: C Wilder-Smith, MD, Brain-Gut Research Group

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 12, 2012

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: December 14, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: IBS; fructose intolerance; GLUT 5; GLUT 2
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Fructose Metabolism, Inborn Errors; Irritable Bowel Syndrome; Fructose Intolerance
• Other Study ID Numbers: GGP1345012; GLUT5 (Other Identifier: Brain-Gut Research Group)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No