Islet Autoantibody Levels Differentiate Progression Trajectories in Individuals With Presymptomatic Type 1 Diabetes




Kwon Bum Chul, Achenbach Peter, Anand Vibha, Frohnert Brigitte I, Hagopian William, Hu Jianying, Koski Eileen, Lernmark Åke, Lou Okivia, Martin Frank, Ng Kenney, Toppari Jorma, Veijola Riitta; on behalf of the T1DI Study Group

PublisherAMER DIABETES ASSOC

2022

Diabetes

DIABETES

DIABETES

71

12

2632

2641

10

0012-1797

1939-327X

DOIhttps://doi.org/10.2337/db22-0360

https://doi.org/10.2337/db22-0360

https://research.utu.fi/converis/portal/detail/Publication/178364980



In our previous data-driven analysis of evolving patterns of islet autoantibodies (IAb) against insulin (IAA), GAD (GADA), and islet antigen 2 (IA-2A), we discovered three trajectories, characterized according to multiple IAb (TR1), IAA (TR2), or GADA (TR3) as the first appearing autoantibodies. Here we examined the evolution of IAb levels within these trajectories in 2,145 IAb-positive participants followed from early life and compared those who progressed to type 1 diabetes (n = 643) with those remaining undiagnosed (n = 1,502). With use of thresholds determined by 5-year diabetes risk, four levels were defined for each IAb and overlaid onto each visit. In diagnosed participants, high IAA levels were seen in TR1 and TR2 at ages <3 years, whereas IAA remained at lower levels in the undiagnosed. Proportions of dwell times (total duration of follow-up at a given level) at the four IAb levels differed between the diagnosed and undiagnosed for GADA and IA-2A in all three trajectories (P < 0.001), but for IAA dwell times differed only within TR2 (P < 0.05). Overall, undiagnosed participantsmore frequently had low IAb levels and later appearance of IAb than diagnosed participants. In conclusion, while it has long been appreciated that the number of autoantibodies is an important predictor of type 1 diabetes, consideration of autoantibody levels within the three autoimmune trajectories improved differentiation of IAb-positive children who progressed to type 1 diabetes from those who did not.


Last updated on 2024-26-11 at 22:23