Type 1 Diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta-cells
dc.contributor.author | Johnson, MB | |
dc.contributor.author | Patel, KA | |
dc.contributor.author | De Franco, E | |
dc.contributor.author | Hagopian, W | |
dc.contributor.author | Killian, M | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Tree, TIM | |
dc.contributor.author | Domingo-Vila, C | |
dc.contributor.author | Hudson, M | |
dc.contributor.author | Hammersley, S | |
dc.contributor.author | Dobbs, R | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Flanagan, SE | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Oram, RA | |
dc.date.accessioned | 2020-07-29T12:46:38Z | |
dc.date.issued | 2020-10-08 | |
dc.description.abstract | Aims/hypothesis Diabetes diagnosed <6 months is usually monogenic. However, 10-15% of cases do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed <6 months without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at very early ages. Methods We studied 166 individuals diagnosed <6 months in whom pathogenic variants in all 26 known genes had been excluded and compared them to individuals with monogenic neonatal diabetes (n=164) or type 1 diabetes diagnosed at 6-24 months (n=152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features. Results We found an excess of patients with high T1D-GRS; 38% (63/166) had a T1D-GRS> 95th centile of healthy controls where 5% (8/166) would be expected if all were monogenic (p<0.0001). Individuals with a high T1D-GRS had a similar rate of autoantibody positivity to type 1 diabetes diagnosed between 6 and 24 months (41% vs. 58%, p=0.2), and had markedly reduced C-peptide (median <3pmol/L within 1 year of diagnosis), reflecting rapid loss of insulin secretion. These individuals also had reduced birthweights (median z-score -0.89) which were lowest in those diagnosed <3 months (-1.98). Conclusions/Interpretation We provide strong evidence that type 1 diabetes can present before age 6 months based on individuals with this extreme-early onset diabetes subtype having the classic features of childhood type 1 diabetes; high genetic risk, autoimmunity and rapid beta-cell loss. The early onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes <6 months. | en_GB |
dc.description.sponsorship | Diabetes Research and Wellness Foundation | en_GB |
dc.identifier.citation | Published online 8 October 2020 | en_GB |
dc.identifier.doi | 10.1007/s00125-020-05276-4 | |
dc.identifier.uri | http://hdl.handle.net/10871/122215 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Verlag | en_GB |
dc.rights | © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.subject | Autoimmunity | en_GB |
dc.subject | Neonatal diabetes | en_GB |
dc.subject | Type 1 diabetes | en_GB |
dc.subject | Genetic risk score | en_GB |
dc.title | Type 1 Diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta-cells | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-07-29T12:46:38Z | |
dc.identifier.issn | 0012-186X | |
dc.description | This is the final version. Available on open access from Springer Verlag via the DOI in this record | en_GB |
dc.identifier.eissn | 1432-0428 | |
dc.identifier.journal | Diabetologia | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-07-24 | |
exeter.funder | ::Diabetes Research and Wellness Foundation | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-07-24 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-07-29T08:35:19Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-10-28T16:31:32Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.