Wednesday, April 24, 2024
4/24/2024
ABSTRACT. The UPMC Clinical Center for the Study of Diabetes after Acute Pancreatitis (UPMC CC), a multidisciplinary research program at the University of Pittsburgh and UPMC, seeks to be a founding member of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). UPMC CC’s organizational structure allows comprehensive characterization of patients with pancreatic disorders from an epidemiological, clinical and translational perspective. Its strengths include outstanding faculty with vast expertise in all areas relevant to the T1DAPC, high patient volumes, infrastructure to conduct high-quality clinical and translational studies, and a track record of strong and successful collaborations, leadership and contributions to multicenter studies and consortiums. The well-established, efficient and effective clinical and research infrastructure for patient accrual, sample processing, data management and transfer, and analysis will support the program. The studies proposed in this application will directly address the overriding objective of the T1DAPC. These explore a new concept that post-acute pancreatitis diabetes mellitus AP (PAP-DM) occurs rapidly because of previously unrecognized ongoing loss of beta cells function after the AP episode is resolved. We will determine how rapidly PAP-DM develops after AP, the natural history of beta-cell function and insulin sensitivity after AP, and the contribution of beta cell autoimmunity to the pathogenesis of DM after AP and chronic pancreatitis (CP). Specific aims: Aim 1) Determine the risk of and characteristics associated with PAP-DM. We will recruit and prospectively follow up non-diabetic patients who recover from AP and compare the incidence of PAP-DM to controls. Aim 2) Determine the natural history of changes in beta cell function after resolution of AP. Using the cohorts of Aim 1 (AP and controls), this aim will determine if clinically silent, ongoing beta cell loss occurs during the first year after AP resolution and whether it correlates with the onset of PAP-DM. Additionally, this aim will determine whether beta cell loss is accompanied by changes in insulin sensitivity and whether it correlates with beta-cell autoimmunity and biomarkers of exocrine pancreas inflammation. Aim 3) Quantify the contribution of beta cell autoimmunity to DM in patients with CP. Existing data and stored serum samples from other NIDDK- sponsored cohorts (NAPS2, PROCEED) will be used to measure beta cell autoantibodies in patients with CP who have DM and compare with patients without DM and non-diabetic healthy controls. The proposed studies will provide crucial information to design personalized-medicine approaches to prevent and treat PAP-DM based on pathophysiology. The studies will lay the groundwork for future research on PAP-DM. To ensure its success and effectiveness, the T1DAPC can count on the solid foundation of world-class faculty, extensive clinical resources, high patient volumes, clinical and translational research experience, ability to work with multiple centers as either leaders or participants in pancreatic research, and record of accomplishments.
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