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An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood

Bonifacio, Ezio ; Weiß, Andreas ; Winkler, Christiane ; Hippich, Markus ; Rewers, Marian J ; Toppari, Jorma ; Lernmark, Åke LU orcid ; She, Jin-Xiong ; Hagopian, William A and Krischer, Jeffrey P , et al. (2021) In Diabetes Care 44(10). p.2260-2268
Abstract

OBJECTIVE: Islet autoimmunity develops before clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for presymptomatic type 1 diabetes.

RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young study prospectively monitored 8,556 genetically at-risk children at 3- to 6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models.

RESULTS: The 5-year risk of developing multiple islet autoantibodies was... (More)

OBJECTIVE: Islet autoimmunity develops before clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for presymptomatic type 1 diabetes.

RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young study prospectively monitored 8,556 genetically at-risk children at 3- to 6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models.

RESULTS: The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% CI 3.8-4.7) at 7.5 months of age and declined to 1.1% (95% CI 0.8-1.3) at a landmark age of 6.25 years (P < 0.0001). Risk decline was slight or absent in single insulin and GAD autoantibody phenotypes. The influence of sex, HLA, and other susceptibility genes on risk subsided with increasing age and was abrogated by age 6 years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5-7 years of age.

CONCLUSIONS: The risk of developing islet autoimmunity declines exponentially with age, and the influence of major genetic factors on this risk is limited to the first few years of life.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
44
issue
10
pages
2260 - 2268
publisher
American Diabetes Association
external identifiers
  • scopus:85141200621
  • pmid:33627366
ISSN
1935-5548
DOI
10.2337/dc20-2122
project
The Environmental Determinants of Diabetes in the Young (TEDDY).
language
English
LU publication?
yes
id
873e9b67-f626-41be-8076-0e18c82c1459
date added to LUP
2021-03-03 08:38:58
date last changed
2024-06-14 19:28:43
@article{873e9b67-f626-41be-8076-0e18c82c1459,
  abstract     = {{<p>OBJECTIVE: Islet autoimmunity develops before clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for presymptomatic type 1 diabetes.</p><p>RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young study prospectively monitored 8,556 genetically at-risk children at 3- to 6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models.</p><p>RESULTS: The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% CI 3.8-4.7) at 7.5 months of age and declined to 1.1% (95% CI 0.8-1.3) at a landmark age of 6.25 years (P &lt; 0.0001). Risk decline was slight or absent in single insulin and GAD autoantibody phenotypes. The influence of sex, HLA, and other susceptibility genes on risk subsided with increasing age and was abrogated by age 6 years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5-7 years of age.</p><p>CONCLUSIONS: The risk of developing islet autoimmunity declines exponentially with age, and the influence of major genetic factors on this risk is limited to the first few years of life.</p>}},
  author       = {{Bonifacio, Ezio and Weiß, Andreas and Winkler, Christiane and Hippich, Markus and Rewers, Marian J and Toppari, Jorma and Lernmark, Åke and She, Jin-Xiong and Hagopian, William A and Krischer, Jeffrey P and Vehik, Kendra and Schatz, Desmond A and Akolkar, Beena and Ziegler, Anette-Gabriele}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{10}},
  pages        = {{2260--2268}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood}},
  url          = {{http://dx.doi.org/10.2337/dc20-2122}},
  doi          = {{10.2337/dc20-2122}},
  volume       = {{44}},
  year         = {{2021}},
}