# Type 1 Diabetes in Acute Pancreatitis Consortium, Pacific Northwest Clinical Center: Immune Pathogenesis of Post-Pancreatitis T1D

> **NIH NIH U01** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2020 · $217,625

## Abstract

Project Summary / Abstract
This application brings together the clinical strengths and large acute pancreatitis patient population of Virginia
Mason Medical Center's Digestive Disease Institute and Benaroya Research Institute's expertise in
autoimmunity and type 1 diabetes to understand the incidence, clinical course, and potential mechanisms of
autoimmune mediated diabetes after acute pancreatitis. The underlying theme of this application is that
knowledge gained from studying autoimmune diabetes after pancreatitis will provide key insights as to
mechanisms of disease in typical type 1 diabetes.
Review and meta-analysis data suggest that almost 40% of individuals will eventually develop diabetes or pre-
diabetes post-acute pancreatitis. There is, however, inconsistency as to populations included, definitions of
endpoints, and duration of follow-up across studies evaluating acute pancreatitis and diabetes. Thus, the true
incidence and natural history of diabetes post-pancreatitis is not clear. Moreover, while generally considered to
be a consequence of necrosis resulting in beta cell injury or destruction, the relationship between acute
pancreatitis necrosis and incidence of diabetes has recently been questioned and there is limited mechanistic
data from either animal or human studies. Thus, the etiopathology of diabetes post-acute pancreatitis is not well
understood.
In contrast, the natural history of typical type 1 diabetes is well described; autoantibodies are seen in genetically
at-risk individuals, some of whom over time develop beta cell death leading to asymptomatic, followed by
symptomatic dysglycemia eventually requiring exogenous insulin therapy. Evidence for the clear role of the
adaptive immune system in this process include the strong genetic association with class II HLA type, the
presence of cellular infiltrates in cadaver specimens, and the ability of adaptive immune therapy to alter disease
course. What is not clear in typical type 1 diabetes is what underlies the initial triggering of the adaptive immune
system. The increasing incidence of disease over time suggests gene-environment interactions leading to beta
cell injury, yet it remains challenging to identify specific triggers. Since pancreatic damage and innate activation
are known components of acute pancreatitis, the development of diabetes in this setting can allow for
investigation as to how acute tissue injury results in autoimmunity and thus serves as a model system to
understand mechanisms resulting in typical type 1 diabetes. In this proposal, we will determine the incidence
and describe the natural history of diabetes and autoimmunity in individuals after acute pancreatitis (Aim 1), test
the hypothesis that acute pancreatitis resolves to an altered immune state in a subset of individuals that
predisposes them to develop islet autoimmunity (Aim 2), and determine if acute pancreatitis associated
autoimmunity results in immune phenotypes similar to that seen in typica...

## Key facts

- **NIH application ID:** 10128243
- **Project number:** 1U01DK127404-01
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** CARLA J GREENBAUM
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $217,625
- **Award type:** 1
- **Project period:** 2020-09-16 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128243

## Citation

> US National Institutes of Health, RePORTER application 10128243, Type 1 Diabetes in Acute Pancreatitis Consortium, Pacific Northwest Clinical Center: Immune Pathogenesis of Post-Pancreatitis T1D (1U01DK127404-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128243. Licensed CC0.

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