Indiana University clinical Center for acute pancreatitis and diabetes clinical research network

Indiana University Indianapolis, Indianapolis IN

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY / ABSTRACT Diabetes mellitus (DM) is a known and underrecognized complication of acute pancreatitis (AP), exhibiting a spectrum of features that overlap with both type 1 and type 2 DM (T1D, T2D). The extent to which immune activation, β cell dysfunction, and insulin resistance occur following AP and the metabolic, imaging, and genetic correlates of these phenotypes have not been well characterized. The Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) was formed in 2020 and tasked participating clinical centers (CC) with proposing studies to address these knowledge gaps. The Indiana University CC is a key contributor to the T1DAPC and the consortium’s primary study, DREAM (Diabetes Related to Acute pancreatitis and its Mechanisms). DREAM is a multicenter, observational cohort study prospectively enrolling adults with a recent episode of AP to investigate the incidence, etiology, and pathophysiology of DM following AP, with emphasis on the autoimmune processes that result in T1D. Participants undergo prospective characterization of glycemic status, islet function, and β cell autoimmunity, as well as serial collection of clinical data, biological specimens, and imaging data to address a number of scientific objectives. In this renewal application, we propose the following specific aims (SA) to meet the goals of RFA-DK-25-017 and the successful renewal of the T1DAPC Consortium: SA #1: Continue our contributions to DREAM. We will utilize state-of-the-art immunologic phenotyping and measurements of β cell function to define the physiologic basis for metabolic dysregulation in DM after AP. In tandem, a biorepository is being developed for undertaking translational, mechanistic, and biomarker investigations. SA #2: Continue our contribution to the T1DAPC ancillary study “DREAM: Metabolic Outcomes Using Novel CGM Metrics” (DREAM- ON). The primary objective of DREAM-ON is to determine whether continuous glucose monitoring (CGM) can predict risk for developing pre-DM and DM or the need for insulin therapy among those who develop DM and whether CGM can provide insight into the pathophysiology and DM subtype following an episode of AP. SA #3: Continue our participation and leading role in the research magnetic resonance imaging (MRI) arm of DREAM, “Imaging Morphology of Pancreas in Diabetic Patients following Acute Pancreatitis” (IMMINENT). IMMINENT utilizes novel quantitative MRI techniques as a non-invasive biomarker to identify patients at risk for DM post- AP. This longitudinal study evaluates pancreatic parenchymal morphologic and pathophysiologic changes following AP in euglycemic, pre-DM, and DM individuals. Imaging phenotypes will be correlated with metabolic and immunological phenotypes. SA #4: Determine whether genetic variation and T1D and T2D genetic burden influence diabetes risk and phenotype following an episode of AP. We hypothesize that underlying genetic variation may provide insight into the risk of developing islet-associated autoimmunity and DM post-AP and could, in part, explain the continuum of metabolic phenotypes observed.