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The Effect of Age on the Progression and Severity of Type 1 Diabetes: Potential Effects on Disease Mechanisms

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

Purpose of Review

To explore the impact of age on type 1 diabetes (T1D) pathogenesis.

Recent Findings

Children progress more rapidly from autoantibody positivity to T1D and have lower C-peptide levels compared to adults. In histological analysis of post-mortem pancreata, younger age of diagnosis is associated with reduced numbers of insulin containing islets and a hyper-immune CD20hi infiltrate. Moreover compared to adults, children exhibit decreased immune regulatory function and increased engagement and trafficking of autoreactive CD8+ T cells, and age-related differences in β cell vulnerability may also contribute to the more aggressive immune phenotype observed in children. To account for some of these differences, HLA and non-HLA genetic loci that influence multiple disease characteristics, including age of onset, are being increasingly characterized.

Summary

The exception of T1D as an autoimmune disease more prevalent in children than adults results from a combination of immune, metabolic, and genetic factors. Age-related differences in T1D pathology have important implications for better tailoring of immunotherapies.

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Funding

This study was financially supported by 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 JDRF research grants awarded to the network of Pancreatic Organ Donors–Virus (nPOD-V) consortium (JDRF 25-2012-516 and JDRF-3-SRA-2017-492-A-N) and a JDRF Career Development Award (5-CDA-2014-221-A-N), an MRC Project Grant (MR/P010695/1) and project grant from Diabetes UK (16/0005480) all to SJR. This work was also supported by NIH grants R01 DK093954 and UC4 DK 104166 (to C.E.M.), U01 DK103180 (to M.R.), VA Merit Award I01BX001733 (to C.E.M.), a JDRF Strategic Research Agreement (2-SRA-2018-493-A-B), and gifts from the Sigma Beta Sorority, the Ball Brothers Foundation, the George and Frances Ball Foundation, and the Holiday Management Foundation, all to C.E.M. R.M. received grants from the JDRF (1-PNF-2014-155-A-V, 2-SRA-2016-164-Q-R), the Agence Nationale de la Recherche (ANR-2015-CE17-0018-01) and by the Innovative Medicines Initiative 2 Joint Undertaking (INNODIA, 115797), which receives support from the EU Horizon 2020 program, the European Federation of Pharmaceutical Industries and Associations, JDRF, and the Helmsley Charitable Trust.

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Authors and Affiliations

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

    Pia Leete & Sarah J. Richardson

  2. INSERM U1016, CNRS UMR8104, Cochin Institute, Sorbonne Paris Cité; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, INSERM and Assistance Publique Hôpitaux de Paris, Paris, France

    Roberto Mallone

  3. Department of Medicine and the Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA

    Jay M. Sosenko

  4. Department of Pediatrics, Baylor College of Medicine and the Texas Children’s Hospital, Houston, TX, USA

    Maria J. Redondo

  5. Departments of Medicine and Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine and the Roudebush VA Medical Center, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, 46202, USA

    Carmella Evans-Molina

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  1. Pia Leete
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  2. Roberto Mallone
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  4. Jay M. Sosenko
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  6. Carmella Evans-Molina
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Correspondence to Carmella Evans-Molina.

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Pia Leete, Roberto Mallone, Sarah J. Richardson, Jay M. Sosenko, Maria J. Redondo, and Carmella Evans-Molina declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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

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Leete, P., Mallone, R., Richardson, S.J. et al. The Effect of Age on the Progression and Severity of Type 1 Diabetes: Potential Effects on Disease Mechanisms. Curr Diab Rep 18, 115 (2018). https://doi.org/10.1007/s11892-018-1083-4

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