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Cited by 54Diabetes Treatment and ManagementPancreatic and Hepatic Oncology ResearchPancreatic function and diabetes

Reanalysis of study of pancreatic effects of incretin therapy: methodological deficiencies

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Bonner‐Weir, S., In't Veld, P. A., Weir, G. C.·2014·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.12257PMC PMC5678976
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Abstract

A recently published study by Butler et al. concluded that incretin treatment had adverse effects on the human type 2 diabetic pancreas including ‘a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia and the latter by α‐cell hyperplasia with the potential for evolution into neuroendocrine tumours’. Incretin therapy has become widely used for type 2 diabetes, so these conclusions have instigated major concerns with regard to patient safety. We reassessed both the clinical case information and virtual microscopy images of the same 34 cases that were used in the Butler study as well as Network for Pancreatic Organ Donation ( nPOD ) cases that were not included. Whereas we would like to stress that it is important to investigate in depth any indication that incretin treatment may lead to inflammation or dysplasia in the pancreas, we find that the data presented in the Butler paper have serious methodological deficiencies that preclude any meaningful conclusions.

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  • Histomorphometric measurement of β-cell area, volume, and mass is often imprecisely defined and complicated by technical inconsistencies.

    “Furthermore, histomorphometric measurement of β-cell area, volume, and mass is often imprecisely defined and complicated by technical inconsistencies ( 59 ).”

    From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [59]

    The 'Methodological problems with quantification' section (page unavailable) describes inconsistent staining and a tissue-area calculation that could distort β-cell area and estimated mass. It examines deficiencies in one study, however; it does not establish that these measurements are often imprecisely defined, or address β-cell volume measurement. (LLM, conf=0.85)

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Authors
Bonner‐Weir, S., In't Veld, P. A., & Weir, G. C.
Affiliations
  • Joslin Diabetes Center (US)
  • Department of Pathology, Diabetes Research Center and JDRF Center for Beta Cell Therapy in Diabetes Vrije Universiteit Brussel Brussels Belgium
Corresponding author
Bonner‐Weir, S.
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2014-01-29
Volume
16
Issue
7
Pages
661-666
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.12257
PMC
PMC5678976
OpenAlex
W2088620867
Cited by
54
References
20
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2018: 2 · 2017: 4 · 2016: 10 · 2015: 12 · 2014: 20
FWCI
12.32
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK093909)
  • Juvenile Diabetes Research Foundation International (1-2011-591)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
incretin-based therapy, type 2 diabetes, pancreatic exocrine function, pancreatic endocrine function, pancreatic neuroendocrine tumors, pancreatic dysplasia, pancreatitis, virtual microscopy, methodological limitations, patient safety
MeSH terms
Diabetes Mellitus, Type 2, Female, Humans, Male, Pancreas, Insulin-Secreting Cells, Incretins

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