Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus

Abstract Introduction The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained. Methods In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower β-cell area and average islet size and density compared to non-T2DM controls (p  Results Compared to both T2DM and non-T2DM controls, mean α-cell area and α/β-ratio was significantly lower in PC cases (p   0.05 vs. Control). Conclusions Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating β-cell failure in PC can be important for our understanding of pathophysiology of PC.