Type 2 Diabetes and Alteration of Immune System of Intestinal Mucosa : Proof of Concept (SIMMUNIDIA)

Type 2 diabetes is the predominant type of diabetes. Because a quiet evolution, it is difficult to have a rapid diagnose. A better knowledge about pathophysiological mechanisms at the origin of type 2 diabetes and about its complications could make it possible to improve the prevention and the treatment of this disease.

Research team developped a new research axis : the microbiota of the intestinal mucosa. They proved a translocation process of intestinal bacteria from the intestinal mucosa to different tissue of the organism implicated in glucose homeostasis. This mechanism is involved in the type 2 diabetes development. A clinical study (MICIMAB) of predictive biomarkers of diabetes and obesity is ongoing.

In parallel, the same team explored the role of intestinal immunity modifications in the bacteria translocation from the gut to the blood circulation. They already have some results on animal model but not yet in human. In animal model, a solid reduction of lymphocytes T CD4 Th17 in the intestinal wall is responsable of the translocation of intestinal bacteria and in the induction of a metabolic inflammation wich promotes insulin resistance, abdominal obesity development and type 2 diabetes.

The aim of this study is to explore this hypothesis in human to have therapeutic solution later.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: Biopsy

• Study Type: Observational
• Enrollment (Actual): 121

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with a diagnoses of type 2 diabetes and patient who do not have a know diabetes diagnose.

Description

Inclusion Criteria:

• Coloscopy indication
• Capacity to give a written informed consent

Exclusion Criteria:

• Type 1 diabetes
• Severe renal failure
• Antecedent of liver fibrosis and/or liver failure
• Antecedent of inflammatory bowel disease, lymphocyte colitis, celiac disease or colon cancer
• Antecedent of obesity surgery or of total colectomy
• Antecedent of documented intestinal ischaemia
• Acute infection the week before the inclusion
• Congenital of acquired immune deficiency
• Chronic viral infection
• Antibiotic of probiotic the month before the coloscopy
• Pregnancy
• Patients participating to another research with an exclusion period
• Patients under guardianship

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with diabetes; Patients with type 2 diabetes will have biopsy during coloscopy.	Other: Biopsy; Ileon and colon biopsy
Control; Patients without type 2 diabetes will have biopsy during coloscopy.	Other: Biopsy; Ileon and colon biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of lymphocyte TCD4 Th17 in colon sample	After colon biopsy, lymphocytes TCD4 Th17 are counted in biopsy sample.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of lymphocyte TCD4 Th17 in ileon sample	After ileon biopsy, lymphocytes TCD4 Th17 are counted in biopsy sample.	Day 1
Number of CD45+ cells in colon sample	After colon biopsy, CD45+ cells are counted in biopsy sample.	Day 1
Number of CD45+ cells in ileon sample	After ileon biopsy, CD45+ cells are counted in biopsy sample.	Day 1
Activation of CD45+ cells in colon sample	After colon biopsy, CD45+ cells are analysed to see their state of activation in biopsy sample.	Day 1
Activation of CD45+ cells in ileon sample	After ileon biopsy, CD45+ cells are analysed to see their state of activation in biopsy sample.	Day 1
Microbiota sequencing in blood sample	Microbiota will be sequencing in blood sample	Day 1
Microbiota quantification in blood sample	Microbiota will be quantified in blood sample	Day 1
Microbiota sequencing in ileon sample	Microbiota will be sequencing in ileon sample	Day 1
Microbiota sequencing in colon sample	Microbiota will be sequencing in colon sample	Day 1
Microbiota quantification in ileon sample	Microbiota will be quantified in ileon sample	Day 1
Microbiota quantification in colon sample	Microbiota will be quantified in colon sample	Day 1
Bacteria production	Culture of biological samples to study the bacteria production	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Pierre Gourdy, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): March 4, 2021
• Study Completion (Actual): March 4, 2021

Study Registration Dates

• First Submitted: June 21, 2016
• First Submitted That Met QC Criteria: June 22, 2016
• First Posted (Estimate): June 23, 2016

Study Record Updates

• Last Update Posted (Actual): February 7, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Coloscopy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: RC31/16/8217

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO