PMID- 32620407 OWN - NLM STAT- MEDLINE DCOM- 20210709 LR - 20210709 IS - 1424-3911 (Electronic) IS - 1424-3903 (Linking) VI - 20 IP - 5 DP - 2020 Jul TI - Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus. PG - 929-935 LID - S1424-3903(20)30161-7 [pii] LID - 10.1016/j.pan.2020.05.010 [doi] AB - 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 beta-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 alpha-cell area was significantly lower and beta/alpha-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 alpha-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating beta-cell failure in PC can be important for our understanding of pathophysiology of PC. CI - Copyright (c) 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved. FAU - Nagpal, Sajan Jiv Singh AU - Nagpal SJS AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, UChicago Medicine, Chicago, IL, USA. FAU - Kandlakunta, Harika AU - Kandlakunta H AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Her, Tracy AU - Her T AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Sharma, Ayush AU - Sharma A AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Sannapaneni, Shilpa AU - Sannapaneni S AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Smyrk, Thomas C AU - Smyrk TC AD - Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Velamala, Pruthvi AU - Velamala P AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Garg, Sushil K AU - Garg SK AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Rakshit, Kuntol AU - Rakshit K AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Majumder, Shounak AU - Majumder S AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. FAU - Chari, Suresh AU - Chari S AD - Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Department of Gastroenterology, Hepatology and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: STChari@mdanderson.org. FAU - Matveyenko, Aleksey AU - Matveyenko A AD - Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Department of Medicine, Division of Endocrinology, Metabolism, Diabetes, and Nutrition, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address: matveyenko.aleksey@mayo.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20200522 PL - Switzerland TA - Pancreatology JT - Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] JID - 100966936 RN - 0 (Amyloid) SB - IM MH - Age Factors MH - Aged MH - Amyloid/metabolism MH - Autopsy MH - Body Mass Index MH - Carcinoma, Pancreatic Ductal/*complications MH - Case-Control Studies MH - Databases, Factual MH - *Diabetes Mellitus, Type 2 MH - Female MH - Glucagon-Secreting Cells/pathology MH - Humans MH - Insulin-Secreting Cells/pathology MH - Islets of Langerhans/pathology MH - Male MH - Middle Aged MH - Pancreatic Diseases/*etiology/pathology MH - Pancreatic Neoplasms/*complications MH - Sex Factors OTO - NOTNLM OT - Diabetes mellitus OT - Endocrine pancreatopathy OT - Islet morphmetrics OT - Pancreatic cancer COIS- Declaration of competing interest All authors certify that they have no potential conflicts of interest related to this article. EDAT- 2020/07/06 06:00 MHDA- 2021/07/10 06:00 CRDT- 2020/07/05 06:00 PHST- 2020/02/10 00:00 [received] PHST- 2020/05/10 00:00 [revised] PHST- 2020/05/13 00:00 [accepted] PHST- 2020/07/06 06:00 [pubmed] PHST- 2021/07/10 06:00 [medline] PHST- 2020/07/05 06:00 [entrez] AID - S1424-3903(20)30161-7 [pii] AID - 10.1016/j.pan.2020.05.010 [doi] PST - ppublish SO - Pancreatology. 2020 Jul;20(5):929-935. doi: 10.1016/j.pan.2020.05.010. Epub 2020 May 22.