Type 3c diabetes associated with chronic pancreatitis: A narrative review

Diabetes associated with pancreatic diseases is termed Type 3c DM (T3cDM). This is a unique entity that shares characteristics of both Type 1 and Type 2 diabetes and has its own characteristics. The prevalence of T3cDM in the western population is less than 10 % of all diabetic patients. The most common cause of T3cDM is chronic pancreatitis (CP) followed by causes such as pancreatic ductal adenocarcinoma, pancreatic agenesis, cystic fibrosis, hemochromatosis, pancreatic resections, and acute necrotizing pancreatitis. In this review, we discuss T3cDM associated with CP. The broad mechanisms related to the development of T3cDM includes insulin deficiency, hepatic insulin resistance, peripheral insulin resistance, and reduced incretin effect. Although insulin deficiency (resulting from secretory defect, islet loss, and gut microbial dysbiosis) and hepatic insulin resistance have been understood, the role of peripheral insulin resistance and impaired incretin effect warrants further validation. The diagnosis of T3cDM in general can be done using the ADA criteria. However, the pancreatic polypeptide response to a mixed meal can differentiate T3cDM from T1DM and T2DM. Among the non-specific treatment, besides abstinence from alcohol and smoking, pancreatic enzyme replacement therapy (PERT) could aid in glycemic control. Among the specific treatment, in patients with mild uncomplicated T3cDM, metformin is the first choice. Insulin sensitizers and secretagogues, and incretin-based therapies are not currently recommended. For severe complicated T3cDM, a basal-bolus approach with insulin therapy is advocated. Promising future approaches includes metabolome-based prediction of progression of prediabetes to T3cDM, and treatment with PP and fecal microbial manipulation.