Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) represent a spectrum of disease, with variable pain burden, often with impaired quality of life and progression to diabetes and pancreatic exocrine insufficiency. The Chronic Pancreatitis Diabetes Pancreatic Cancer (CPDPC) consortium – known in the next funding cycle as the Chronic Pancreatitis Clinical Research Consortium (CPCRC)-- is transforming clinical care for pancreatitis through defining the natural history of disease, developing biomarkers for progression, and ultimately setting the stage for future treatments for affected patients. 

 

The University of Minnesota (UMN) brings together a strong multidisciplinary team with Pediatrics, Internal Medicine, and Surgery, and will contribute to the CPCRC through enrollment and retention of patients in consortium studies, academic leadership, and collaboration with other CPCRC sites. 

 

The first aim of our CPCRC involvement is to recruit and follow participants in the longitudinal cohorts for pediatric pancreatitis (“INSPPIRE-2”) and adult pancreatitis (“PROCEED”) and provide academic expertise and leadership in the consortium. We are unique in our contributions to both INSPPIRE-2 and PROCEED, reflecting our balanced Pediatric and Adult Medicine team. We will capitalize on unique expertise and resources at UMN to propose new ancillary studies for our second and third aims of this proposal. 

 

In our second aim, we will determine the burden of hypoglycemia and glycemic lability, and adequacy of counterregulatory responses to hypoglycemia in adults with RAP and CP and post-pancreatitis diabetes. This is important because individuals with this form of diabetes are clinically felt to be at increased risk for hypoglycemia, but there is surprisingly little evidence in the current literature to support or refute this clinical impression. Understanding hypoglycemia risks and physiology is important in guiding diabetes treatment. 

 

In our third aim, we will use collected biospecimens and data from the PROCEED cohort to determine differences in diversity indices, distance matrices, and relative abundance and uniqueness of the fecal microbiome in participants with RAP/CP vs those without pancreas disease, and determine if there are signatures of gut dysbiosis in those who develop pain or diabetes as complications of disease. 

 

We hypothesize that these unique microbiome patterns may serve as a biomarker of disease or contribute mechanistically to disease progression. To accomplish this third aim, we will add new co-investigators to our team with established expertise in microbiome research in the settings of diabetes and gastrointestinal disease. Collectively, this work is clinically significant in defining disease pathophysiology and developing future therapeutic strategies for CP.

 

Public Health Relevance Statement

Project Narrative Chronic pancreatitis and recurrent acute pancreatitis represent a spectrum of disease that causes significant pain, decreased quality of life, and disability for those individuals (adults and children) affected. Unfortunately, the disease course is often unpredictable, difficult to treat, and often without any curative therapy. By collaborating with other academic institutions in the Chronic Pancreatitis Clinical Research Consortium (CPCRC), the University of Minnesota will contribute to defining the pathophysiology of the disease, identifying biomarkers of disease progression, and ultimately developing prevention and treatment strategies to help affected patients.