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

Ezio Bonifacio; Andreas Weiß; Christiane Winkler; Markus Hippich; Marian J Rewers; Jorma Toppari; Åke Lernmark; Jin-Xiong She; William A Hagopian; Jeffrey P Krischer; Kendra Vehik; Desmond A Schatz; Beena Akolkar; Anette-Gabriele Ziegler; TEDDY Study Group

doi:10.2337/dc20-2122

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

Ezio Bonifacio, Andreas Weiß, Christiane Winkler, Markus Hippich, Marian J Rewers, Jorma Toppari, Åke Lernmark, Jin-Xiong She, William A Hagopian, Jeffrey P Krischer, Kendra Vehik, Desmond A Schatz, Beena Akolkar, Anette-Gabriele Ziegler, TEDDY Study Group

Research output: Contribution to journal › Article › Scientific › peer-review

37 Citations (Scopus)

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 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.

Original language	English
Journal	Diabetes care
DOIs	https://doi.org/10.2337/dc20-2122
Publication status	E-pub ahead of print - 24 Feb 2021
Publication type	A1 Journal article-refereed

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Bonifacio, E., Weiß, A., Winkler, C., Hippich, M., Rewers, M. J., Toppari, J., Lernmark, Å., She, J.-X., Hagopian, W. A., Krischer, J. P., Vehik, K., Schatz, D. A., Akolkar, B., Ziegler, A.-G., & TEDDY Study Group (2021). An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood. Diabetes care. Advance online publication. https://doi.org/10.2337/dc20-2122

@article{648c9dca56bd48d28a9be13f4140b575,

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

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 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.",

author = "Ezio Bonifacio and Andreas Wei{\ss} and Christiane Winkler and Markus Hippich and Rewers, {Marian J} and Jorma Toppari and {\AA}ke Lernmark and Jin-Xiong She and Hagopian, {William A} and Krischer, {Jeffrey P} and Kendra Vehik and Schatz, {Desmond A} and Beena Akolkar and Anette-Gabriele Ziegler and {TEDDY Study Group} and Suvi Ahonen and Mari {\AA}kerlund and Leena Hakola and Heikki Hy{\"o}ty and Sinikka J{\"a}minki and Mikael Knip and Mirva Koreasalo and Kalle Kurppa and Jarita Kyt{\"o}l{\"a} and Katri Lindfors and Jutta Laiho and Maria L{\"o}nnrot and Markus Mattila and Tiina Niininen and Sari Niinist{\"o} and Sami Oikarinen and Jenna Rautanen and Anne Riikonen and Miia Pekkola and Suvi Virtanen",

note = "{\textcopyright} 2021 by the American Diabetes Association.",

year = "2021",

month = feb,

day = "24",

doi = "10.2337/dc20-2122",

language = "English",

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TY - JOUR

T1 - An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood

AU - Bonifacio, Ezio

AU - Weiß, Andreas

AU - Winkler, Christiane

AU - Hippich, Markus

AU - Rewers, Marian J

AU - Toppari, Jorma

AU - Lernmark, Åke

AU - She, Jin-Xiong

AU - Hagopian, William A

AU - Krischer, Jeffrey P

AU - Vehik, Kendra

AU - Schatz, Desmond A

AU - Akolkar, Beena

AU - Ziegler, Anette-Gabriele

AU - TEDDY Study Group

AU - Ahonen, Suvi

AU - Åkerlund, Mari

AU - Hakola, Leena

AU - Hyöty, Heikki

AU - Jäminki, Sinikka

AU - Knip, Mikael

AU - Koreasalo, Mirva

AU - Kurppa, Kalle

AU - Kytölä, Jarita

AU - Lindfors, Katri

AU - Laiho, Jutta

AU - Lönnrot, Maria

AU - Mattila, Markus

AU - Niininen, Tiina

AU - Niinistö, Sari

AU - Oikarinen, Sami

AU - Rautanen, Jenna

AU - Riikonen, Anne

AU - Pekkola, Miia

AU - Virtanen, Suvi

PY - 2021/2/24

Y1 - 2021/2/24

N2 - 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.

AB - 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.

U2 - 10.2337/dc20-2122

DO - 10.2337/dc20-2122

M3 - Article

C2 - 33627366

SN - 0149-5992

JO - Diabetes care

JF - Diabetes care

ER -

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

Abstract

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