Four birth-cohort studies in the U.S. (DAISY, DEWIT), Sweden (DiPiS) and Finland (DIPP) were initiated in 1990s to early 2000. General population newborns and young first-degree relatives (FDR) of T1D patients, preselected on increased HLA risk, were followed for islet autoantibodies (AAb)and T1D. We harmonized their common variables, including AAb to insulin, IA-2, GAD, or ZnT8, HLA-DR-DQ risk genotypes, socio-demographics, diet, family history, glucose/HbA1c and anthropometric measures. The combined cohort included 22,312 subjects with AAb measured in 256,243 visits (mean 11±10 per subject) at 3-12 month intervals. During follow-up, 2279 (10%) subjects developed at least one AAb, 914 (4%) multiple AAb and 603 (3%) T1D. The cumulative risk of T1D differed by the number of AAb at seroconversion (Figure). T1D developed in 26% (95% CI 24-32%) of 1AAb, 62% (55-68%) of 2AAb and 84% (75-88%) of >=3AAb positive subjects in the 15y after seroconversion. T1D risk varied by HLA genotype: 40% (35-48%) in DR3/4-DQ2/8, 22% (18-31%) in DR4/x-DQ8/x and 21% (18-35%) in DR3/x-DQ2/x of 1AAb subjects and, respectively, in 82% (68-88%), 61%(50-65%)and 87% (32-98%)of 2AAb subjects. Once ≥2 AAb positive, HLA genotype was less predictive of progression to T1D. This harmonized dataset offers an unparalleled opportunity to validate and improve upon reported risk estimates for T1D development via novel analytical methods.
V. Anand: None. B. Liu: None. M. Ghalwash: None. E. Koski: None. K. Ng: None. J.L. Dunne: None. W. Hagopian: Research Support; Self; Novo Nordisk A/S. M. Lundgren: None. Å. Lernmark: None. J. Ilonen: None. R. Veijola: None. M. Rewers: None.
JDRF
