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Pancreas Pathology During the Natural History of Type 1 Diabetes

  • Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)
  • Published:
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Abstract

Purpose of review

We provide an overview of pancreas pathology in type 1 diabetes (T1D) in the context of its clinical stages.

Recent findings

Recent studies of pancreata from organ donors with T1D and non-diabetic donors expressing T1D-associated autoantibodies reveal pathological changes/disease mechanisms beyond the well-known loss of β cells and lymphocytic infiltrates of the islets (insulitis), including β-cell stress, dysfunction, and viral infections. Pancreas pathology evolves through disease stages, is asynchronous, and demonstrates a chronic disease that remains active years after diagnosis. Critically, β-cell loss is not complete at onset, although young age is associated with increased severity.

Summary

The recognition of multiple pathogenic alterations and the chronic nature of disease mechanisms during and after the development of T1D inform improved clinical trial design and reveal additional targets for therapeutic manipulation, in the context of an expanded time window for intervention.

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Abbreviations

AAb+:

Autoantibody positive

EADB:

Exeter Archival Diabetes Biobank

ER:

Endoplasmic reticulum

DiViD:

Diabetes Virus Detection Study

GAD:

Glutamic acid decarboxylase

HA:

Hyaluronan

HLAI:

Human leukocyte antigen class I

IA-2:

Islet antigen-2

ICI:

Insulin-containing islet

IDI:

Insulin-deficient islet

MODY:

Maturity onset diabetes of the young

NOD:

Non-obese diabetic mouse

nPOD:

Network for Pancreatic Organ Donors with Diabetes

T2D:

Type 2 diabetes

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Acknowledgments

We would like to acknowledge Dr. Pia Leete (University of Exeter, UK) for providing immunofluorescence images. We are pleased to acknowledge financial support from the European Union’s Seventh Framework Programme PEVNET (FP7/2007–2013) under grant agreement number 261441. The participants of the PEVNET consortium are described at http://www.uta.fi/med/pevnet/publications.html. Additional support was from a Diabetes Research Wellness Foundation Non-Clinical Research Fellowship and, since 2014, a JDRF Career Development Award (5-CDA-2014-221-A-N) to S.J.R., a JDRF research grant awarded to the nPOD-V consortium (JDRF 25-2012-516), which also supports T.R.-C. and A.P. Research reviewed here involves patients from the EADB, DiViD, and nPOD collections; nPOD, The Network for Pancreatic Organ Donors with Diabetes, a collaborative type 1 diabetes research project. nPOD and A.P. are supported by grants from JDRF (5-SRA-2018-557-Q-R) and The Leona M. and Barry B. Helmsley Charitable Trust (2015PG-T1D052 and 2018PG-T1D060). Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at www.jdrfnpod.org/our-partners.php.

Author information

Authors and Affiliations

  1. Institute for Diabetes Research, Helmholtz Diabetes Center at Helmholtz Zentrum München, Munich, Germany

    Teresa Rodriguez-Calvo

  2. Islet Biology Exeter (IBEx), Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK

    Sarah J. Richardson

  3. Diabetes Research Institute, Department of Medicine, Division of Endocrinology, Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA

    Alberto Pugliese

  4. Diabetes Research Institute, 1450 NW 10th Avenue, Miami, FL, 33136, USA

    Alberto Pugliese

Authors
  1. Teresa Rodriguez-Calvo
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  2. Sarah J. Richardson
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  3. Alberto Pugliese
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Corresponding author

Correspondence to Alberto Pugliese.

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Conflict of Interest

T.R.-C., S.J.R., and A.P. declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

Studies reviewed in this article involved organ donors or deceased patients (not considered human subjects from the regulatory point of view), and living patients. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed in the animal studies reviewed in this article.

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This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes

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Rodriguez-Calvo, T., Richardson, S.J. & Pugliese, A. Pancreas Pathology During the Natural History of Type 1 Diabetes. Curr Diab Rep 18, 124 (2018). https://doi.org/10.1007/s11892-018-1084-3

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  • DOI: https://doi.org/10.1007/s11892-018-1084-3

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