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

Type2 Diabetes Clinical Trial

Official title:

Enteroendocrine Cells in Healthy Individuals and Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03044860
• Other study ID #: Endocrinemapping
• Status: Completed
• Phase: N/A
• First received: January 10, 2017
• Last updated: February 14, 2017
• Start date: March 2011
• Est. completion date: June 2012

Study information

• Verified date: February 2017
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)