TY - JOUR
T1 - The Effect of Age on the Progression and Severity of Type 1 Diabetes
T2 - Potential Effects on Disease Mechanisms
AU - Leete, Pia
AU - Mallone, Roberto
AU - Richardson, Sarah J.
AU - Sosenko, Jay M.
AU - Redondo, Maria J.
AU - Evans-Molina, Carmella
N1 - Funding Information:
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.
Publisher Copyright:
© 2018, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Age
KW - Autoimmunity
KW - C-peptide
KW - Type 1 diabetes
KW - β cell
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U2 - 10.1007/s11892-018-1083-4
DO - 10.1007/s11892-018-1083-4
M3 - Review article
C2 - 30259209
AN - SCOPUS:85053904227
VL - 18
JO - Current Diabetes Reports
JF - Current Diabetes Reports
SN - 1534-4827
IS - 11
M1 - 115
ER -