P-18: Longitudinal changes in islet autoimmunity and glycaemia in paediatric first-degree relatives with positive islet autoantibody
B Bombaci, O Pollé, A E Hendriks, L Overbergh, M Knip, C Mathieu, M L Marcovecchio, , INNODIA consortiumAbstract
Introduction
INNODIA established a European cohort of first-degree relatives (FDR) to improve prediction of progression and staging of type 1 diabetes (T1D).
Objectives
We aimed to characterise islet autoantibody and glycaemic patterns in the INNODIA paediatric FDR cohort, and to identify factors associated with progression to Stage 3 T1D.
Methods
The INNODIA cohort includes FDR (age 1–45 years) screened across 13 European countries and followed for up to 4 years with 6-monthly oral glucose tolerance tests, HbA1c, and annual islet autoantibody (IAb). Data for the paediatric cohort (<18 years) were analysed by age groups <10 and 10–18 years using Kaplan–Meier curves and Cox regressions.
Results
Of the 5341 FDR screened, 204 children and adolescents positive for ≥1 IAb (age: 10.0 [6.0–14.0] years; 53.4% male) agreed to participate in follow-up. Overall, 110 (53.9%) had a single IAb and 94 (46.1%) ≥2 IAb; at baseline, 31.9% were at Stage 1, 13.7% at Stage 2, and 2.9% at Stage 3. Among participants with a single IAb at screening, progression to multiple IAb was more frequent in those <10 years (19.2% vs 3.4%; p=0.013) (Figure 1A). Overall, 19.1% progressed to Stage 3, with no significant difference between age groups (Figure 1B). Participants with multiple IAb had higher progression rates than those with a single IAb (36.2% vs 4.5%; log-rank p<0.001). In multivariable Cox models, Stage 1 (HR 6.7 [1.4-31.3], p=0.016), Stage 2 (HR 24.7 [5.4-113.8], p<0.001), and IA-2A positivity at baseline (HR 9.3 [2.06-41.9], p=0.004) independently predicted progression to Stage 3. Presence of all four IAb (HR 10.2 [2.2-46.9], p=0.003) conferred a similar risk to IA-2A positivity.
Conclusions
Baseline disease stage and IA-2A positivity were the strongest predictors of Stage 3 T1D progression. Children <10 years showed higher seroconversion rates, supporting age-specific monitoring strategies.