Role of Intestinal Inflammation in the Pathogenesis of Type 1 Diabetes

This purpose of this study is to determine if activation of a person's immune system in the small intestine could be a contributing cause of Type 1 Diabetes.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Procedure: Upper endoscopy with small bowel biopsies and brushings.; Other: Blood draw; Other: Stool sample

Detailed Description

There is a large body of literature hinting at a role of the gut in Type One Diabetes (T1D) pathogenesis. However, to the best of our knowledge there is no definitive evidence to date conclusively demonstrating a link. The only way to test this hypothesis is to have access to the intestinal tissue of T1D patients at very early stages when beta-islet cell destruction is still ongoing. Furthermore, to prepare for large prospective studies it is critical to determine whether there is a peripheral blood signature for intestinal inflammation. Finally, because enteroviral infections have been implicated in T1D pathogenesis, this study provides a unique opportunity to determine whether there is a dysregulated response to innate stimuli associated with viral infections and whether evidence of transcriptional signatures indicative of viral infections in the gut is correlated with disease. Finally, we will take advantage of this pilot study to collect samples that can be used for microbiome, virome and metabolic studies.

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Type 1 Diabetes, diagnosed within 6 months

Description

For the Diabetes Cohort:

Inclusion Criteria:

• Initial diagnosis for Type 1 Diabetes Mellitus (DM) must be within the past 6 months.
• Clinical criteria used to diagnose T1D include at least some of the following : Diabetic ketoacidosis, Polyuria, Polydipsia, weight loss, need for insulin from diagnosis, BMI less than 30, C-peptide < 200 pmol/L or 0.6 ng/ml, Presence of Type 1 Diabetes Associated Antibodies

Exclusion Criteria:

• Subjects on antibiotics, proton pump inhibitors, aspirin, non-steroidal anti-inflammatory drugs, alcohol intake within 48 hours, a bowel preparation with 4 weeks of the studies, and smokers
• Subjects will be asked not to take any probiotics in the week before testing.
• Any known intestinal inflammation such as Gastroesophageal Reflux Disease (GERD), eosinophilic esophagitis, and inflammatory bowel disease.
• Prior gastrointestinal surgery (other than appendectomy)
• Ongoing use of antiplatelet agents or anticoagulants.
• Diabetic patients should not have a prior history of or family history of Celiac Disease (CD).
• Subjects unable to provide informed consent
• The presence of any medical or psychological condition that could interfere with the safe performance of the upper endoscopy.
• Females cannot be pregnant

For the Healthy Control Cohort:

Inclusion Criteria:

- Healthy subjects

Exclusion Criteria:

• Controls should not have a family history of DM or CD
• Subjects on antibiotics, proton pump inhibitors, aspirin, non-steroidal anti-inflammatory drugs, alcohol intake within 48 hours, a bowel preparation with 4 weeks of the studies, and smokers
• Subjects will be asked not to take any probiotics in the week before testing.
• Any known intestinal inflammation such as Gastroesophageal Reflux Disease (GERD), eosinophilic esophagitis, and inflammatory bowel disease.
• Prior gastrointestinal surgery (other than appendectomy)
• Ongoing use of antiplatelet agents or anticoagulants.
• Subjects unable to provide informed consent
• The presence of any medical or psychological condition that could interfere with the safe performance of the upper endoscopy.
• Females cannot be pregnant

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Type 1 Diabetes; Subjects will have an upper endoscopy with small bowel biopsies and brushings. Blood will be collected for serum, DNA, and peripheral blood mononuclear cells (PBMC). Stool samples will be collected at baseline for future microbiome and virome studies.	Procedure: Upper endoscopy with small bowel biopsies and brushings.; Other: Blood draw; Blood will be collected for serum, DNA, and peripheral blood mononuclear cells (PBMC).; Other: Stool sample; Stool samples will be collected at baseline for future microbiome and virome studies.
Healthy Control Group; Subjects will have an upper endoscopy with small bowel biopsies and brushings. Blood will be collected for serum, DNA, and peripheral blood mononuclear cells (PBMC). Stool samples will be collected at baseline for future microbiome and virome studies.	Procedure: Upper endoscopy with small bowel biopsies and brushings.; Other: Blood draw; Blood will be collected for serum, DNA, and peripheral blood mononuclear cells (PBMC).; Other: Stool sample; Stool samples will be collected at baseline for future microbiome and virome studies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Interleukin 15 (IL-15) Expression	baseline, 3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Juvenile Diabetes Research Foundation; University of Chicago; Harvard University
• Investigators: Principal Investigator: Joseph Murray, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): June 19, 2019
• Study Completion (Actual): June 19, 2019

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: September 9, 2013
• First Posted (Estimate): September 12, 2013

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Inflammation
• Other Study ID Numbers: 12-003972