Autoantibodies to truncated GAD(96-585) antigen stratify risk of early insulin requirement in adult-onset diabetes

Sian L Grace, Kathleen M Gillespie, Claire L Williams, Vito Lampasona, Peter Achenbach, Ewan Pearson, Alistair J K Williams, Anna E Long, Timothy McDonald, Angus Jones*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

25 Downloads (Pure)

Abstract

We investigated whether characterisation of full-length (f-)GADA responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA positive participants diagnosed with type 2 diabetes, we assessed associations of truncated (t-)GADA positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA positive without early insulin in comparison to f-GADA positive type 2 diabetes requiring insulin within 5 years, and type 1 diabetes (75% vs. 91% and 95% respectively, p<0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher type 1 diabetes genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, p=0.003), lower C-peptide (1156 pmol/L vs. 4289 pmol/L, p=1x10-7), and increased IA-2A positivity (23% vs. 6%, p=0.03). In survival analysis, t-GADA positivity was associated with early insulin requirement compared with those only positive for f-GADA, independently from age of diagnosis, f-GADA titre and duration of diabetes [adjusted HR 5.7 (95% CI 1.4, 23.5), p=0.017]. The testing of t-GADA in f-GADA positive individuals with type 2 diabetes identifies those who have genetic and clinical characteristics comparable to type 1 diabetes and stratifies those at higher risk of early insulin requirement.
Original languageEnglish
Pages (from-to)1583-1591
Number of pages9
JournalDiabetes
Volume73
Issue number10
Early online date8 Jul 2024
DOIs
Publication statusPublished - 1 Oct 2024

Bibliographical note

Publisher Copyright:
© 2024 by the American Diabetes Association.

Fingerprint

Dive into the research topics of 'Autoantibodies to truncated GAD(96-585) antigen stratify risk of early insulin requirement in adult-onset diabetes'. Together they form a unique fingerprint.

Cite this