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 R. Pearson, Alistair J.K. Williams, Anna E. Long, Timothy J. McDonald, Angus G. Jones (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated whether characterization of full-length GAD (f-GADA) antibody (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 GADA (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 with f-GADA–positive type 2 diabetes requiring insulin within 5 years, and T1D (75% vs. 91% and 95% respectively, P < 0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher T1D genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, P = 0.003), lower C-peptide (1,156 pmol/L vs. 4,289 pmol/L, P = 1 × 10-7), and increased IA-2 antigen 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 titer, and duration of diabetes (adjusted hazard ratio 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 T1D and stratifies those at higher risk of early insulin requirement.

Original languageEnglish
Pages (from-to)1583-1591
Number of pages9
JournalDiabetes
Volume73
Issue number10
DOIs
Publication statusPublished - Oct 2024

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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