Multicenter Assessment of the Pancreas in Type 1 Diabetes

Study Overview
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Brief Summary
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The overall goal of this research is to develop and validate standard operating procedures (SOP) to assess the human pancreas in individuals with type 1 diabetes (T1D) and other forms of diabetes using advanced, quantitative magnetic resonance imaging (MRI) approaches.

Detailed Description
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This research applies magnetic resonance imaging (MRI) techniques to study the pancreas of individuals with type 1 diabetes (T1D) and other forms of diabetes. Recent studies have demonstrated reduced pancreatic volume is present within months of T1D diagnosis in children, adolescents, and adults, and in non-diabetic individuals expressing islet autoantibodies that portend the development of T1D. As the pancreatic beta cells constitute only 1-2% of the pancreas, the degree of reduction in pancreas volume at disease onset suggests exocrine involvement, challenging the established paradigm of T1D being solely a disease of the endocrine pancreas. These unexpected findings raise fundamental questions that challenge our understanding of T1D pathogenesis. These changes in pancreatic volume and size before and soon after onset of T1D, as detected by MRI, appear to be a marker of the T1D pathogenic disease process. There is an urgent need to determine whether similar observations can be obtained at different centers using different MRI platforms. Discovery of unknown changes may lead to new ways to treat disease. The MRI techniques may also be useful for following how T1D is progressing in different people, determining whether new drugs are effective, and ultimately detecting T1D in people earlier than currently possible.

Official Title
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Multicenter Assessment of the Pancreas in Type 1 Diabetes

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Other: Non-contrast magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects at least 8 years of age Subjects with T1D must be imaged within 100 days of their date of diagnosis Subjects must be able to read and provide assent/informed written consent Exclusion Criteria: Subjects with pancreatitis, cystic fibrosis, pancreatic adenocarcinoma, or neuroendocrine tumors Subjects who have any type of bioimplant activated by mechanical, electronic, or magnetic means because such devices may be displaced or malfunction Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced Subjects who are pregnant or breast-feeding. Urine pregnancy test will be performed on women of child bearing potential who are not practicing appropriate contraception measures or menstruating. Subjects who exhibit significant anxiety and/or claustrophobia Subjects incapable of giving assent/informed written consent For controls: subjects who have first degree relatives with T1D

Ages Eligible for Study
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Minimum Age: 8 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 |
| --- | --- |
| T1D<br>Individuals with type 1 diabetes | Other: Non-contrast magnetic resonance imaging<br>* subjects lie in an MRI machine (non-contrast) for 30 minutes while we take pictures of their pancreas<br>|
| Control<br>Individuals without type 1 diabetes | Other: Non-contrast magnetic resonance imaging<br>* subjects lie in an MRI machine (non-contrast) for 30 minutes while we take pictures of their pancreas<br>|
| Aab+<br>Individuals without type 1 diabetes who possess 2+ type 1 diabetes-related autoantibodies | Other: Non-contrast magnetic resonance imaging<br>* subjects lie in an MRI machine (non-contrast) for 30 minutes while we take pictures of their pancreas<br>|
| MODY<br>Individuals with monogenic diabetes, or maturity-onset diabetes of the young (MODY) | Other: Non-contrast magnetic resonance imaging<br>* subjects lie in an MRI machine (non-contrast) for 30 minutes while we take pictures of their pancreas<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreas Volume Index | Size of the pancreas determined by longitudinal MRI, normalized to subject weight | Duration of subject's participation in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI of pancreas - Apparent Diffusion Coefficient | MRI texture of pancreas | Duration of subject's participation in the study | 
| T1D Genetic Risk Score | Saliva will be collected and used to make DNA to determine a T1D genetic risk score | Once, at study enrollment | 
| T1D Autoantibodies | Control subjects who enroll will be asked to have their blood drawn to determine their T1D autoantibody status | Once, at study enrollment | 
| Urinary C-peptide/creatinine | Urine may be collected on all participants to assess urinary C-peptide/creatinine ratio | Once for controls, at study enrollment; Possibly at each visit for T1D |