Role of Intestinal Inflammation in the Pathogenesis of Type 1 Diabetes

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.

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.

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