O-05: Index60 as a predictor of type 1 diabetes progression in first-degree relatives with positive islet autoantibodies
A Clark, B Bombaci, L Overbergh, C Mathieu, M L Marcovecchio, , INNODIA ConsortiumAbstract
Introduction
Screening programmes to identify early-stage type 1 diabetes (T1D) are expanding. Measures of beta-cell function may improve identification of individuals at highest risk of disease progression. One such metric is Index60, a composite score derived from glucose and C-peptide, which has shown promise in individuals with positive islet autoantibodies (IAb).
Objectives
To evaluate the predictive value of baseline Index60 for progression to stage 3 T1D in the INNODIA cohort of first-degree relatives (FDR) with positive IAb.
Methods
FDR aged 1–45 years were screened for four IAb, and those positive for at least one IAb were invited to participate in the INNODIA Natural History Study, which included 6-monthly oral glucose tolerance tests (OGTT) for 4 years. Index60 was calculated using OGTT glucose and C-peptide. A receiver operating characteristic curve was used to identify an optimal Index60 threshold for progression to stage 3 T1D, and survival analyses were performed to assess its predictive value for stage 3 T1D.
Results
A total of 347 (54.2% female) participants completed a baseline OGTT at a median age of 15.5 years (1.5 - 45.2). Of these, 162 (47%) had an Index60 above the optimal threshold of -0.40 (High-Index 60). Participants with a high-Index60 were younger (median age 12.0 vs 25.2 years, p<0.001) and were more likely to have ≥2 IAb (30.2% vs 69.8%, p<0.001) compared to those with a low-Index60.
During follow up, 41 participants (12%) progressed to stage 3 T1D. A high-Index60 was strongly associated with progression (Figure 1), with a Hazard Ratio of 6.4 (95%CI 2.2-18.9, p<0.001), after adjustment for age, BMI and IAb number.
Conclusions
In this large cohort of FDR, a higher baseline Index60 was an independent predictor of progression to stage 3 T1D. Index60 may aid risk stratification and targeted monitoring of IAb+ individuals, who may benefit from future preventative interventions.