Anatomical and Physiological Characterisation of the Gut Endocrine Cells in Healthy and in Patients With Type 2 Diabetes
Primary Purpose
Type2 Diabetes
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Double-balloon enteroscopy (DBE) with biopsy retrieval
Sponsored by
About this trial
This is an interventional basic science trial for Type2 Diabetes
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Type 2 diabetes
Healthy
Arm Description
Adult patients with type 2 diabetes undergoing double-balloon enteroscopy (DBE) with biopsy retrieval using a DBE-device.
Adult subjects without type 2 diabetes undergoing double-balloon enteroscopy (DBE) with biopsy retrieval using a DBE-device.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT03044860
First Posted
January 10, 2017
Last Updated
February 14, 2017
Sponsor
University Hospital, Gentofte, Copenhagen
1. Study Identification
Unique Protocol Identification Number
NCT03044860
Brief Title
Anatomical and Physiological Characterisation of the Gut Endocrine Cells in Healthy and in Patients With Type 2 Diabetes
Official Title
Enteroendocrine Cells in Healthy Individuals and Patients With Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Gentofte, Copenhagen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Type 2 diabetes
Arm Type
Experimental
Arm Description
Adult patients with type 2 diabetes undergoing double-balloon enteroscopy (DBE) with biopsy retrieval using a DBE-device.
Arm Title
Healthy
Arm Type
Experimental
Arm Description
Adult subjects without type 2 diabetes undergoing double-balloon enteroscopy (DBE) with biopsy retrieval using a DBE-device.
Intervention Type
Procedure
Intervention Name(s)
Double-balloon enteroscopy (DBE) with biopsy retrieval
Intervention Description
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
Primary Outcome Measure Information:
Title
Evaluation of enteroendocrine cells (density and mRNA expression) in the intestinal tract.
Description
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.
Time Frame
Cross-sectional study. Each participant went through two study days (upper and lower double-ballon enteroscopy, respectively)
Title
Evaluation of differences in enteroendocrine cells (density and mRNA expression) along the intestinal tract of healthy individuals compared with type 2 diabetes patients.
Description
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.
Time Frame
Cross-sectional study. Each participant went through two study days (upper and lower double-ballon enteroscopy, respectively)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34036343
Citation
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.
Results Reference
derived
PubMed Identifier
28956082
Citation
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.
Results Reference
derived
Learn more about this trial
Anatomical and Physiological Characterisation of the Gut Endocrine Cells in Healthy and in Patients With Type 2 Diabetes
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