The objective of this University of Florida/Advent Health proposal within the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) is to establish a longitudinal prospective cohort of patients with acute and acute relapsing pancreatitis in order to investigate the incidence, pathophysiology, mechanisms, environmental and biologic risk factors, and predictors of subsequent diabetes. The Diabetes Institute at UF (UFDI) and the Advent Health Translational Research Institute have the resources and capabilities required to perform comprehensive genetic, immunologic, metabolic, histologic, and functional testing to dissect the various mechanisms underlying diabetes following acute pancreatitis. Our proposal addresses four key needs of the T1DAPC. 1) A platform for recruiting large numbers of subjects with acute or acute relapsing pancreatitis. The combined volumes of both health systems approach 2,000 patients admitted with acute pancreatitis yearly. The clinical expertise and existing clinical research support structure is experienced and capable, and the two Institutes have the scientific expertise to help define and support the whole variety of mechanistic studies that will be undertaken; 2) Mechanistic studies of diabetes after acute pancreatitis including a) measuring autoantibody markers of islet autoimmunity after acute pancreatitis (subaim 1a); b) assessing subjects? type 1 diabetes genetic risk leveraging a custom genotyping array and log additive genetic risk score (subaim 1b); comprehensively characterizing ??-cell function after acute pancreatitis (subaim 1c); and d) analyzing the imaging features of acute pancreatitis which predict the subsequent development of diabetes (subaim 1d); 3) A consortium opportunity to study human subjects prior to the development of acute pancreatitis, that occurring after endoscopic retrograde cholangiopancreatography (ERCP). UFHealth and AdventHealth perform approximately 2,400 of these procedures yearly, and with the participation of other T1DAPC centers, a sub- cohort could be assembled with biospecimens and imaging data prior to the development of acute pancreatitis, providing a very useful comparison population for future analyses. 4) Collecting a bank of human pancreata from subjects with previous pancreatitis. The Network for Pancreatic Organ donors with Diabetes (nPOD), housed at the UFID, collects and processes transplant-grade pancreata and other tissues from organ procurement organizations (OPOs) across the U.S. and provides them for investigators around the world. We will leverage this infrastructure, along with that of a large local OPO associated with AdventHealth, to obtain organs from individuals with a history of acute pancreatitis. This will provide a unique resource for the T1DAPC, to interrogate the mechanisms of diabetes in tissue, which is not readily accessible in living subjects. This can provide a clinicopathologic correlation for the T1DAPC mechanistic studies. We believe the types of analyses proposed will be necessary for the work of the T1DAPC, and we are able to fully support these aims or related aims selected by the T1DAPC.
Acute pancreatitis is common and increasing in both incidence and prevalence in the United States, with risk of subsequently developing exocrine insufficiency and/or diabetes approaching 30%. Hence, efforts to understand the mechanisms, risk factors, and predictors of diabetes following acute pancreatitis are of significant public health importance to facilitate the development of strategies for early detection, prevention, and effective management. Through the framework provided by the Type 1 Diabetes Acute Pancreatitis Consortium (T1DAPC), the combined University of Florida and AdventHealth team will serve as a high-volume center contributing to patient enrollment and collection of biological samples for mechanistic and clinical studies to characterize diabetes pathogenesis following acute pancreatitis, ultimately in support of future efforts to identify accurate biomarkers and more effective therapies.
