Comparative Characteristics of the Course of Chronic Pancreatitis and the Development of Type 3C Diabetes Mellitus (T3CDM)

Abstract

Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease of the pancreas, characterized by persistent immune activation, acinar cell damage, and eventual endocrine dysfunction. Type 3c diabetes mellitus (T3cDM), a secondary form of diabetes resulting from pancreatic exocrine pathology, develops in the context of CP via a multifaceted pathogenic process. This review provides a comparative analysis of the clinical and molecular progression from CP to T3cDM. Key mechanisms include activation of the innate immune system (TLR4, NLRP3 inflammasome), chronic endoplasmic reticulum stress and unfolded protein response (UPR), apoptotic signaling in β-cells, and involvement of fibrogenic and pro-inflammatory pathways such as TGF-β/Smad, JAK/STAT3, PI3K/Akt, and MAPK. Epigenetic modifications and dysbiosis further amplify inflammation and fibrosis. The unique clinical features of T3cDM—distinct from types 1 and 2 diabetes—necessitate the development of personalized therapeutic approaches targeting inflammation, fibrosis, and microbiota. This work highlights the importance of early recognition of molecular biomarkers and signaling cascades for improved diagnostic and treatment strategies in pancreatogenic diabetes.