@article{5c03db5e10a44a9695b690b3a6d8b27d,
title = "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 < 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",
author = "Nagpal, {Sajan Jiv Singh} and Harika Kandlakunta and Tracy Her and Ayush Sharma and Shilpa Sannapaneni and Smyrk, {Thomas C.} and Pruthvi Velamala and Garg, {Sushil K.} and Kuntol Rakshit and Shounak Majumder and Suresh Chari and Aleksey Matveyenko",
note = "Funding Information: This publication was made possible by a grant from the Chellaram Foundation (Suresh Chari), National Institutes of Health U01 Consortium for Study of Chronic Pancreatitis, Diabetes and Pancreatic cancer (CPDPDC) (Suresh T. Chari), Kenner Family Research Fund (Suresh T. Chari), National Institutes of Health ( 2R01DK098468 ) (Aleksey Matveyenko) and CTSA Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS) , a component of the National Institutes of Health (NIH) . Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH or any other funding source. Funding Information: This publication was made possible by a grant from the Chellaram Foundation (Suresh Chari), National Institutes of Health U01 Consortium for Study of Chronic Pancreatitis, Diabetes and Pancreatic cancer (CPDPDC) (Suresh T. Chari), Kenner Family Research Fund (Suresh T. Chari), National Institutes of Health (2R01DK098468) (Aleksey V. Matveyenko) and CTSA Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS) , a component of the National Institutes of HealtH (NIH) . Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH or any other funding source. Publisher Copyright: {\textcopyright} 2020 IAP and EPC Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jul,
doi = "10.1016/j.pan.2020.05.010",
language = "English (US)",
volume = "20",
pages = "929--935",
journal = "Pancreatology",
issn = "1424-3903",
publisher = "S. Karger AG",
number = "5",
}