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

Benaroya Research Inst At Virginia Mason, Seattle WA

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY Acute Pancreatitis (AP) accounts for over 300,000 hospitalizations in the United States per year. Along with the morbidity and mortality occurring at the time of AP hospitalization, in recent years, evidence has indicated that development of diabetes mellitus (DM) is relatively common after an episode of acute pancreatitis; estimates range from 10-40% of people with AP developing DM. As evident from the wide-ranging estimates, the degree of risk of DM, and factors driving that risk, have not been definitively identified. Characterization of the type of DM that develops after AP, whether Type 1 diabetes, Type 2 diabetes, or Type 3c diabetes (associated with destruction of the exocrine pancreas), has not been done in large, prospective cohorts. Retrospective studies/meta-analyses of DM suffer from a difficulty in appropriate classification of diabetes via review of electronic health records, making it challenging to have full confidence in these studies. The role of the immune system in AP, and in the development of DM after AP, also remains poorly understood, with few publications detailing the immune response to AP using modern immunophenotyping methods. For these reasons, the Type 1 Diabetes after Acute Pancreatitis Consortium (T1DAPC) was initiated to develop and conduct a longitudinal prospective study into the incidence, risk factors, and immune and endocrine variables associated with the development of DM after AP. The 10 clinical centers of the T1DAPC have now enrolled over 750 participants into a clinical research protocol called Diabetes Related to Acute pancreatitis and its Mechanisms (DREAM). The DREAM study calls for enrollment of participants within 90 days of an AP hospitalization, with longitudinal follow-up for 5 years to identify changes in glucose tolerance and the development of diabetes. It also seeks to characterize the endocrine and immunologic features associated with AP and post-AP diabetes. The Benaroya Research Institute (BRI) Clinical Center has been a highly collaborative partner in both the consortium as a whole and in the DREAM study in particular. Our investigators lead the consortium’s Immunology Working Group and are members of the Pancreatitis, Diabetes, Recruitment and Retention, Biospecimens, Publications, and Protocol Writing Groups. We helped develop the study protocol and its aims, and since the study was initiated have been one of the highest recruiting centers with 92 participants enrolled to date. We have a high rate of retention into long term follow-up and were among the first sites to see a participant at 3 years of follow-up. Here, we propose to continue and extend our efforts in support of this study via the following 2 aims. AIM 1: Complete follow up visits for all DREAM participants at the BRI T1DAPC Clinical Center, enabling the DREAM study to address its primary outcome of defining the frequency and characteristics of DM development after AP. AIM 2: Discover and validate immune signatures associated with resolution of AP and development of DM.