# University of Minnesota Clinical Center for the Study of Acute Pancreatitis and Diabetes

> **NIH NIH U01** · UNIVERSITY OF MINNESOTA · 2020 · $270,229

## Abstract

Abstract
Patients with a history of acute pancreatitis (AP) are at high risk for developing diabetes mellitus (DM),
affecting about 1 in 4 patients after AP. Clinical risk factors are poorly understood, and mechanisms leading to
development of DM after AP are unknown. We propose to study risk for and mechanisms underlying
development of DM after AP; specifically we will study the contributions of beta cell autoimmunity, defects in
insulin secretion, and insulin resistance to DM after AP.
In type 1 diabetes mellitus (T1DM) insulin deficiency results from targeted autoimmune destruction of the islet
β-cells; this autoimmunity is triggered by unknown environmental exposures in genetically susceptible
individuals. We hypothesize that tissue injury combined with an altered inflammatory milieu during AP activates
β-cell autoimmunity (T1DM) in a subset of patients with AP-related DM. Our preliminary data collectively
suggests an increased signal of β-cell autoimmunity in patients with recurrent AP or chronic pancreatitis and
DM. We hypothesize that patients who develop DM after AP will have reduced insulin secretion (due to
pancreatic injury), reduced insulin sensitivity, and a subset will have β-cell autoimmunity.
Our overall goal is to establish a carefully phenotyped multi-center longitudinal cohort of adults diagnosed with
AP to determine clinical risk factors for DM, define metabolic dysfunction in AP-DM, and determine the
immunologic contributions to AP-DM. The University of Minnesota-Clinical Center investigators are leaders in
the fields of AP, DM, and T1DM immunology and are ideally suited to address the consortium objectives. In
Aim 1, we will identify, recruit, and enroll adults (N=1250) consortium-wide at 0 to 3 months after a first
episode of acute pancreatitis for a longitudinal study to advance our understanding of progression to DM after
AP. We will determine clinical risk factors for DM after AP. In Aim 2, we will define mechanistic mechanisms of
AP-related DM by studying 250 patients after AP (from Aim 1) with mixed meal tolerance and frequent sample
intravenous glucose tolerance tests to measure insulin secretion and insulin sensitivity. In Aim 3, we will
define immunologic mechanisms of disease by determining the contribution of β-cell autoimmunity in
development of DM after AP. We will perform HLA-typing and β-cell autoantibodies in the entire cohort from
Aim 1 and assess cellular autoimmunity with T-cell and B-cell tetramers in a subset of 60 subjects selected by
DM and AAb status. A separate tissue biobank will be used to evaluate islet infiltrates in recurrent AP.
This work will contribute significantly to both our understanding of pancreatogenic DM and T1DM. In the setting
of AP, better defining the pathophysiologic mechanisms of disease is critical to improving treatment and
delaying or preventing progression to DM. For T1DM, this work provides an avenue to better identify an
important role for islet β-cells as a key trigger fo...

## Key facts

- **NIH application ID:** 10124783
- **Project number:** 1U01DK127367-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Melena D. Bellin
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $270,229
- **Award type:** 1
- **Project period:** 2020-09-17 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124783

## Citation

> US National Institutes of Health, RePORTER application 10124783, University of Minnesota Clinical Center for the Study of Acute Pancreatitis and Diabetes (1U01DK127367-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10124783. Licensed CC0.

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