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Circulating C-Peptide Levels in Living Children and Young People and Pancreatic Beta Cell Loss in Pancreas Donors Across Type 1 Diabetes Disease Duration

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posted on 02.05.2022, 14:09 by Alice L.J. Carr, Jamie R.J. Inshaw, Christine S. Flaxman, Pia Leete, Rebecca C. Wyatt, Lydia A. Russell, Matthew Palmer, Dmytro Prasolov, Thomas Worthington, Bethany Hull, Linda S. Wicker, David B. Dunger, Richard A. Oram, Noel G. Morgan, John A. Todd, Sarah J. Richardson, Rachel E.J. Besser

C-peptide declines in type 1 diabetes although many long-duration patients retain low, but detectable levels. Histological analyses confirm that beta cells can remain following type 1 diabetes onset. We explored the trends observed in C-peptide decline in UK Genetic Resource Investigating Diabetes (UK GRID) cohort (N=4,079), with beta cell loss in pancreas donors from the network for Pancreatic Organ donors with Diabetes (nPOD) biobank and the Exeter Archival Diabetes Biobank (EADB) (combined N=235), stratified by recently reported age at diagnosis endotypes (< 7, 7-12, ≥ 13 years) across increasing diabetes durations. The proportion of individuals with detectable C-peptide declined beyond the first year after diagnosis, but this was most marked in the youngest age group (< 1 year duration: age < 7 years: 18/20 (90%), 7-12 years: 107/110 (97%), ≥ 13 years: 58/61 (95%) versus. 1-5 years post diagnosis: < 7 years: 172/522 (33%), 7-12 years: 604/995 (61%), ≥ 13 years: 225/289 (78%)). A similar profile was observed in beta cell loss, with those diagnosed at younger ages experiencing more rapid loss of islets containing insulin-positive (insulin+) beta cells 

< 1 year post diagnosis: age < 7 years: 23/26 (88%), 7-12 years: 32/33 (97%), ≥ 13 years: 22/25 (88%) versus. 1-5 years post diagnosis: < 7 years: 1/12 (8.3%) ,7-12 years: 7/13 (54%), ≥ 13 years: 7/8 (88%)). These data should be considered in the planning and interpretation of intervention trials designed to promote beta cell retention and function. 

Funding

The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), through funding of REJB. REJB is also funded through the JDRF/Wellcome’s Strategic Award. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We are grateful to Diabetes UK for financial support via project grant 16/0005480 (NGM, SJR, PL) and to JDRF for a Career Development Award (5-CDA-2014-221-A-N). RAO is funded by a Diabetes UK Harry Keen Fellowship (16/0005529). This research was performed with the support of the Network for Pancreatic Organ donors with Diabetes (nPOD; RRID:SCR_014641), a collaborative type 1 diabetes research project sponsored by JDRF (nPOD: 5-SRA-2018-557-Q-R) and The Leona M. & Harry B. Helmsley Charitable Trust (Grant#2018PG-T1D053), a strategic award to the Diabetes and Inflammation Laboratory from the JDRF (4-SRA-2017-473-A-A) and the Wellcome (107212/A/15/Z). The content and views expressed are the responsibility of the authors and do not necessarily reflect the official view of nPOD. Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners/.

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