Introduction to the Issue: Acute Pancreatitis and related Metabolic Complications

Acute pancreatitis (AP) is among the most common gastrointestinal causes of hospitalization. In 2018, there were 288,220 hospitalizations in the United States where AP was listed as the primary diagnosis¹. Historically, the management of AP (and related clinical research) has largely focused on the acute phase of disease (e.g., predicting disease severity, fluid resuscitation, diet, organ failure, and local complications). Similarly, basic science research has focused mainly on understanding the mechanisms of initiation of pancreatic injury and severity of AP. Long-term metabolic sequalae of AP including diabetes and/or exocrine pancreatic insufficiency were only considered in the context of risk due to pancreatic necrosis in the setting of moderate or severe AP. The Revised Atlanta Classification framework has been instrumental in standardizing the nomenclature for diagnosis and local complications², allowing for comparison of data between different studies.

Research in the past few years has drawn attention to the long-term sequelae in patients with mild or non-necrotizing AP. As an example, the risk of future diabetes is noted to be significantly increased in these patients³ and a substantial proportion may require insulin therapy^4,5. Noting these developments, in the most recent guidelines, the American Diabetes Association has recommended screening for diabetes in patients with AP 3–6 months after an episode and then yearly thereafter⁶. Similar to diabetes, a subset of patients with mild AP will also exocrine insufficiency during follow-up and may benefit from pancreatic enzyme replacement therapy⁷. The development of these metabolic complications in patients with mild clinical severity suggest the need for a more nuanced understanding of pathogenesis than simply attributing this to pancreatic necrosis. Other important sequelae following AP include persistence of poor quality of life⁸ and increased risk of pancreatic cancer⁹.

Recognizing the limited understanding of the risk and mechanisms of diabetes after AP, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) established a consortium in 2020 called the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) to address the knowledge gaps in this field¹⁰. The T1DAPC has launched a prospective cohort study titled Diabetes Related to Acute Pancreatitis and its Mechanisms (DREAM) in 2022, which aims to address many of the knowledge gaps, including the risk and factors associated with development of diabetes after AP, characterization of beta cell function and endocrine alterations after AP, and understanding the immunologic mechanisms of diabetes after AP including the contribution of beta-cell autoimmunity. The study will also evaluate morphologic changes in the pancreas after AP with magnetic resonance imaging (MRI). Further rational and detailed methodology of the different components of the DREAM study have been previously described^11–17.

The current issue was developed to further elaborate the gaps in our understanding of the development AP and its related metabolic complications. Articles featured in the current issue are authored by T1DAPC investigators. Each provides up to date information on the selected topics related to AP which the practicing clinicians will find informative in their day to day practice. Where applicable, the authors highlight key knowledge gaps and how the ongoing research in the DREAM study or its ancillary studies aim to address these gaps.