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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 LU orcid ; Lou, Olivia and Martin, Frank , et al. (2022) In Diabetes 71(12). p.2632-2641
Abstract

Our previous data-driven analysis of evolving patterns of islet autoantibodies (IAbs) against insulin (IAA), glutamic acid decarboxylase (GADA) and islet antigen 2 (IA-2A) discovered three trajectories characterized by either multiple IAbs (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) to those remaining undiagnosed (n=1,502). Using thresholds determined by 5-year diabetes risk, four levels were defined for each IAb and overlayed onto each visit. In diagnosed participants, high IAA levels were seen in TR1 and TR2 at ages... (More)

Our previous data-driven analysis of evolving patterns of islet autoantibodies (IAbs) against insulin (IAA), glutamic acid decarboxylase (GADA) and islet antigen 2 (IA-2A) discovered three trajectories characterized by either multiple IAbs (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) to those remaining undiagnosed (n=1,502). Using thresholds determined by 5-year diabetes risk, four levels were defined for each IAb and overlayed 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 participants more frequently had low IAb levels and later appearance of IAb than diagnosed participants. In conclusion, while it has been long 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.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
71
issue
12
pages
2632 - 2641
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85143664683
  • pmid:36112006
ISSN
1939-327X
DOI
10.2337/db22-0360
language
English
LU publication?
yes
additional info
© 2022 by the American Diabetes Association.
id
e6a9fab3-d1fb-48b4-a344-e088b8dae81c
date added to LUP
2022-09-21 20:58:49
date last changed
2025-03-17 23:53:07
@article{e6a9fab3-d1fb-48b4-a344-e088b8dae81c,
  abstract     = {{<p>Our previous data-driven analysis of evolving patterns of islet autoantibodies (IAbs) against insulin (IAA), glutamic acid decarboxylase (GADA) and islet antigen 2 (IA-2A) discovered three trajectories characterized by either multiple IAbs (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) to those remaining undiagnosed (n=1,502). Using thresholds determined by 5-year diabetes risk, four levels were defined for each IAb and overlayed onto each visit. In diagnosed participants, high IAA levels were seen in TR1 and TR2 at ages &lt;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&lt;0.001), but for IAA dwell times differed only within TR2 (p&lt;0.05). Overall, undiagnosed participants more frequently had low IAb levels and later appearance of IAb than diagnosed participants. In conclusion, while it has been long 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.</p>}},
  author       = {{Kwon, Bum Chul and Achenbach, Peter and Anand, Vibha and Frohnert, Brigitte I and Hagopian, William and Hu, Jianying and Koski, Eileen and Lernmark, Åke and Lou, Olivia and Martin, Frank and Ng, Kenney and Toppari, Jorma and Veijola, Riitta}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{12}},
  pages        = {{2632--2641}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Islet Autoantibody Levels Differentiate Progression Trajectories in Individuals with Presymptomatic Type 1 Diabetes}},
  url          = {{http://dx.doi.org/10.2337/db22-0360}},
  doi          = {{10.2337/db22-0360}},
  volume       = {{71}},
  year         = {{2022}},
}