Mechanisms of diabetes from acute pancreatitis in African Americans and Hispanics Acute pancreatitis (AP) leads to oxidative and inflammatory injury, ensuing parenchymal damage, exocrine and/or endocrine insufficiencies including the development of diabetes. While AP increases the risk of the development of diabetes, the type of diabetes, either type 1 diabetes (T1D, autoimmune) as compared to other forms of diabetes, is not clear. Considering diabetes is a major health disparity in our country, understanding AP-driven diabetes is needed in racially diverse populations. Additionally, the risk factors or the mechanisms lead to AP driven diabetes is also unclear. Importantly, the gut microbiota is a novel factor linked to the genesis of both T1D and type 2 diabetes (T2D), yet its role in AP driven diabetes is not known. Moreover, in our diverse patient population, the compositional profiles of gut microbiota are not well defined. Our proposal leverages our extensive, multiple institutional, cohort of patients which is predominantly African American (AA) and Hispanic and our broad, multidiscplinary team with a range of expertise in clinical pancreatology and diabetes, gut microbiome, diet and health disparities research. In sum, the goal of our proposal is three-fold: 1) to define in our diverse patient population that is predominantly AA and Hispanic, the relationship between AP to T1D, and other forms of diabetes, and the factors associated with development of diabetes, and to mechanistically define 2) how diet, specifically enriched in animal protein and fat (DH-APF), through its interaction with the gut microbiota, impacts AP-driven diabetes, and 3) how fiber from the diet, through the generation of short chain fatty acids (SCFAs), a recently recognized factor identified in the genesis of T1D and T2D, mediates AP-driven T1D.
We have established ?The Chicago Clinical Center? for Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), bringing together multi-disciplinary team members from major academic centers located in Cook County, one of the most populous, racially and ethnically diverse counties in the United States to help the Consortium to build a diverse clinical cohort. In addition, we propose studies to define the contribution of diet enriched in animal protein and fat and low in fiber, through its interaction with the gut microbiota, to development of diabetes, especially type 1 diabetes following acute pancreatitis. Improving our understanding of these relationships can help to identify novel biomarkers for acute pancreatitis and diabetes that are applicable to general population and to develop effective preventive and treatment strategies.
