Anatomical and Physiological Characterisation of the Gut Endocrine Cells in Healthy and in Patients With Type 2 Diabetes

Enteroendocrine Cells in Healthy Individuals and Patients With Type 2 Diabetes

Investigation of the anatomical distribution of enteroendocrine cells by a systematic approach along the entire human intestinal tract in healthy individuals and patients with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes
• Intervention / Treatment: Procedure: Double-balloon enteroscopy (DBE) with biopsy retrieval

Detailed Description

Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis, but knowledge of their distribution in man is sparse and it is unknown whether alterations occur in type 2 diabetes. Twelve patients with type 2 diabetes and 12 age and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from every ~30 cm of the small intestine and specific locations in the large intestine. The investigators evaluated the distribution of enteroendocrine cells (using IHC staining for their specific hormonal products) and evaluated mRNA expression of the corresponding genes along the entire intestinal tract in patients with type 2 diabetes and in healthy individuals.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

Type 2 diabetes patients

• Diagnosis of type 2 diabetes (at least 3 months prior to study inclusion)
• Treatment with diet counseling alone or combined with an glucose-lowering drugs: metformin or sulphonylurea
• Caucasian ethnicity
• Age >25 and <70 years
• Normal hemoglobin
• Negative for autoantibodies to glutamic acid decarboxylase (GAD-65) and islet cell autoantibodies (ICA).

Healthy individuals

• Fasting plasma glucose <6.0 mM
• Plasma glucose 2 hours after a 75 g-oral glucose tolerance test <7.8 mM
• Negative for GAD-65 antibodies and ICA
• Caucasian ethnicity
• Age >25 and <70 years
• Normal hemoglobin

Exclusion criteria:

Type 2 diabetes patients

• Liver disease (evaluated by alanine aminotransferase and/or aspartate aminotransferase >2 times normal value)
• Treatment with dipeptidyl peptidase 4 inhibitors or medicine that could not be paused for 12 hours
• Previous hysterectomy, appendectomy, cholecystectomy or caesarean
• Sleep apnea
• American Society of Anesthesiologists class >3
• Allergy to soy protein or eggs
• BMI >35 kg/m2 or any other condition that would contraindicate propofol sedation or enteroscopy.

Healthy individuals

• Liver disease (evaluated by alanine aminotransferase and/or aspartate aminotransferase >2 times normal value)
• Liver disease (evaluated by alanine aminotransferase and/or aspartate aminotransferase >2 times normal value)
• Treatment with dipeptidyl peptidase 4 inhibitors or medicine that could not be paused for 12 hours
• Previous hysterectomy, appendectomy, cholecystectomy or caesarean
• Sleep apnea
• American Society of Anesthesiologists class >3
• Allergy to soy protein or eggs
• BMI >35 kg/m2 or any other condition that would contraindicate propofol sedation or enteroscopy
• First-degree relative(s) with type 1 or type 2 diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Type 2 diabetes; Adult patients with type 2 diabetes undergoing double-balloon enteroscopy (DBE) with biopsy retrieval using a DBE-device.	Procedure: Double-balloon enteroscopy (DBE) with biopsy retrieval; With the use of a double-balloon enteroscopy device, study participants underwent upper and lower enteroscopies with mucosal biopsy mucosal biopsy retrieval from every ~30 cm of the small intestine and specific locations in the large intestine
Experimental: Healthy; Adult subjects without type 2 diabetes undergoing double-balloon enteroscopy (DBE) with biopsy retrieval using a DBE-device.	Procedure: Double-balloon enteroscopy (DBE) with biopsy retrieval; With the use of a double-balloon enteroscopy device, study participants underwent upper and lower enteroscopies with mucosal biopsy mucosal biopsy retrieval from every ~30 cm of the small intestine and specific locations in the large intestine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of enteroendocrine cells (density and mRNA expression) in the intestinal tract.	Using a double-balloon enteroscopy device, mucosal biopsies are obtained from the entire intestinal tract in 12 healthy individuals and 12 patients diagnosed with type 2 diabetes. The biopsies are analysed using immunohistochemistry (IHC) and mRNA expression analysis. Positively stained enteroendocrine cells (from IHC) are counted and divided by the epithelial area providing 'density' (cells/mm2). The data obtained from cell count and mRNA expression analysis present the variation in number of enteroendocrine cells (density) and the expression of hormonal products along the intestinal tract.	Cross-sectional study. Each participant went through two study days (upper and lower double-ballon enteroscopy, respectively)
Evaluation of differences in enteroendocrine cells (density and mRNA expression) along the intestinal tract of healthy individuals compared with type 2 diabetes patients.	Using a double-balloon enteroscopy device, mucosal biopsies are obtained from the entire intestinal tract in 12 healthy individuals and 12 patients diagnosed with type 2 diabetes. The biopsies are analysed using immunohistochemistry (IHC) and mRNA expression analysis. Positively stained enteroendocrine cells (from IHC) are counted and divided by the epithelial area providing 'density' (cells/mm2). Cell count (density) and mRNA expression data obtained from the healthy individuals and type 2 diabetes patietns are compared to evaluate potential differences between the two groups.	Cross-sectional study. Each participant went through two study days (upper and lower double-ballon enteroscopy, respectively)

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen

Publications and helpful links

General Publications

• Gilliam-Vigh H, Jorsal T, Rehfeld JF, Pedersen J, Poulsen SS, Vilsboll T, Knop FK. Expression of Cholecystokinin and its Receptors in the Intestinal Tract of Type 2 Diabetes Patients and Healthy Controls. J Clin Endocrinol Metab. 2021 Jul 13;106(8):2164-2170. doi: 10.1210/clinem/dgab367.
• Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalboge LS, Vilmann P, Hassan H, Hendel JW, Poulsen SS, Holst JJ, Vilsboll T, Knop FK. Enteroendocrine K and L cells in healthy and type 2 diabetic individuals. Diabetologia. 2018 Feb;61(2):284-294. doi: 10.1007/s00125-017-4450-9. Epub 2017 Sep 28.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: Endocrinemapping

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED