This is an application for renewal of Clinical Center designation of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). The Greater Los Angeles Clinical Center has provided considerable leadership in the organization and progress of the CPDPC. Dr. Pandol serves as co-chair of the Steering Committee and Dr. Goodarzi co-chairs the Type 3c Working Group. We have excelled in recruitment and retention of participants in the cohort studies implemented through the CPDPC designed to elucidate the natural history and develop means of diagnosis, treatment and clinical management of chronic pancreatitis (CP) and its complications in children and adults, and to determine the pathogenic interrelationships of diabetes and pancreatic cancer and develop the means of early diagnosis and management of pancreatic cancer. In addition, we have been performing a number ancillary and associated studies to support the overall goals of CPDPC, including: 1. Epidemiologic studies defining risk factors for pancreatic cancer and the natural history of CP; 2. Determining that genetic susceptibility for type 2 diabetes is a strong risk factor for diabetes associated with CP; 3. Developing liquid biopsy assays for aiding in the diagnosis of pancreatic cancer and CP; 4. Investigating mechanisms of pancreatitis and pancreatic cancer for rational pharmaceutical treatments; and 5. Conducting pilot clinical trials for treatment of recurrent acute and chronic pancreatitis. For the next phase of the CPDPC we are committed to the following Specific Aims: 1. Continue recruitment and retention of subjects in CPDPC cohort studies (PROCEED, INSPPIRE 2, NOD, DETECT) in existing and additional study sites, as well as increase diversity in the study population. 2. Continue currently supported ancillary studies to further develop risk factor models combined with liquid biopsy assays for early diagnosis of chronic pancreatitis and pancreatic cancer, and advance mechanism- based treatments and clinical trials for recurrent acute and chronic pancreatitis and pancreatic cancer. 3. Build models that combine clinical features with genetic susceptibility to allow the prediction of future development of diabetes in patients with chronic pancreatitis. 4. Determine the role of pancreatic enzyme replacement in regulating glucose homeostasis in patients with chronic pancreatitis and diabetes, with or without pancreatic exocrine insufficiency. 5. Use existing and annotated pre-diagnostic CT scans to develop artificial intelligence-based techniques for highly sensitive and specific methods for CT-based early pancreatic cancer detection. Our Center involves Cedars-Sinai Medical Center, UCLA Medical Center, the VA Greater Los Angeles Healthcare System and the University of Southern California/Los Angeles Public Health System with an organizational structure designed to expand recruitment into cohort studies of CPDPC with increased diversity and to facilitate o...