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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
University Hospital, Gentofte, Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type2 Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

    First Posted
    January 10, 2017
    Last Updated
    February 14, 2017
    Sponsor
    University Hospital, Gentofte, Copenhagen
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    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

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

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