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

Pancreatology. 2020 Jul;20(5):929-935. doi: 10.1016/j.pan.2020.05.010. Epub 2020 May 22.

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 < 0.05).

Results: Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and β/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (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.

Keywords: Diabetes mellitus; Endocrine pancreatopathy; Islet morphmetrics; Pancreatic cancer.

Publication types

  • Comparative Study

MeSH terms

  • Age Factors
  • Aged
  • Amyloid / metabolism
  • Autopsy
  • Body Mass Index
  • Carcinoma, Pancreatic Ductal / complications*
  • Case-Control Studies
  • Databases, Factual
  • Diabetes Mellitus, Type 2*
  • Female
  • Glucagon-Secreting Cells / pathology
  • Humans
  • Insulin-Secreting Cells / pathology
  • Islets of Langerhans / pathology
  • Male
  • Middle Aged
  • Pancreatic Diseases / etiology*
  • Pancreatic Diseases / pathology
  • Pancreatic Neoplasms / complications*
  • Sex Factors

Substances

  • Amyloid