Circulating Extracellular Vesicles Released by Human Islets of Langerhans

Study Overview
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Brief Summary
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Beta-cells release extracellular vesicles (EV) and exosomes under normal and pathophysiologic conditions. These EV contain beta-cell specific autoantigens which may trigger the immune response at the initiation of type 1 diabetes. In this study, beta-cell derived EV will be detected and characterized in human blood samples.

Detailed Description
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Adult subjects will be recruited with: new onset type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) as well as islet transplant candidates. Blood samples will be collected at defined intervals to determine beta-cell specific EV and determine the utility of this biomarker as a measure of beta-cell stress or injury.

Official Title
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Immune Response to Extracellular Vesicles Released by Human Islets of Langerhans

Conditions
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Type1 Diabetes Mellitus, Type2 Diabetes, Islet Cell Transplantation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 Diagnosis of type 1 diabetes or type 2 diabetes or islet transplant recipient Exclusion Criteria: Unknown diagnosis of diabetes Active infection Immunocompromised Organ transplant recipients not including candidates for islet transplant HIV+ Hepatitis C+ Hepatitis B surface antigen+ Known concurrent malignancy Known pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| New onset T1DM<br>Newly diagnosed Type I diabetic patients who are hyperglycemic but still C-peptide positive | |
| T1DM<br>Patients with established type I diabetes. they are hyperglycemic but C-peptide negative | |
| T2DM<br>Patients with established type II diabetes. | |
| Islet Transplant<br>Patients who received an islet transplantation for type I diabetes | |
| Healthy Volunteers<br>Normoglycemic healthy volunteers | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the levels of circulating EVs | Based on well-known EV markers, subject plasma samples will be characterized to determine whether these EVs are detectable using small particle flow cytometry. | 2 years | 
| Determine whether these EVs contain islet-specific antigens | EVs will be further characterized using small particle flow cytometry for known islet-specific antigens such as GAD65 and ZnT8 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mutivariate analysis will be performed with patient parameters and EV parameters | Correlate levels of EVs containing islet specific markers to patient parameters like age, duration of established diabetes, levels of autoantibodies, | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extracellular vesicles, Autoimmunity, Beta-cell injury