Cedars Sinai Clinical Center of the Type 1 Diabetes in Acute Pancreatitis Consortium

This is an application for renewal of Clinical Center designation from the Cedars-Sinai Center for the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). The Cedars-Sinai Clinical Center has provided considerable leadership in the progress of the main cohort study of the T1DAPC, called the Diabetes Related to Acute Pancreatitis and its Mechanisms (DREAM) study. Dr. Pandol co-chairs the Ancillary and Associated Studies Committee while Dr. Goodarzi chairs the Genetics Interest Group, leading the Consortium’s initiatives to define the genetic risk of diabetes occurring after acute pancreatitis. We have successfully addressed challenges in recruitment and retention of subjects in the cohort studies to significantly improve our performance, as described in this application. Moreover, we have proposed and obtained approval for two key ancillary studies (described in Aims 2 and 3). For the next phase of the Consortium, we are committed to the following Specific Aims: Specific Aim 1. Continue recruitment and retention of participants in the DREAM study. We will describe our progress in recruitment to date and how we have addressed challenges to improve recruitment and retention. Specific Aim 2. Identify biomarkers and pathways of progression of acute pancreatitis to recurrent acute and chronic pancreatitis. Identification of patients with a high probability of progressing pancreatic disease and molecular pathways mediating progression is a major goal for the field. This project is designed to use a mass spectroscopy proteomics-based model for prediction of progression as well as identify molecular targets that can be developed into therapeutics for prevention of progression after an acute episode of pancreatitis. Specific Aim 3. Evaluate genetic risk factors for diabetes in patients with AP or RAP. Large-scale genome-wide association study (GWAS) meta-analyses have identified many non-overlapping SNPs that predispose to T1DM or T2DM. These SNPs will be genotyped in DREAM participants with AP or RAP who do not have diabetes at enrollment. We will determine whether genetic risk is a major contributor to the future development of diabetes. Given that genetic risk scores based on GWAS SNPs can distinguish between different types of diabetes, we anticipate that the genetic profile will be able not only to improve diabetes prediction but also allow the type of diabetes (T1DM vs T2DM) to be predicted. We will carry out the aims with a leading interdisciplinary team committed to collaborative research with other Centers and the Data Coordinating Center (DCC) of the Consortium to continue to address and resolve the outstanding gaps in the field.