Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study

Environmental Determinants of Diabetes in the Young (TEDDY) Group

doi:10.2337/dc22-1359

Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study

Environmental Determinants of Diabetes in the Young (TEDDY) Group

Steno Diabetes Center Copenhagen

Abstract

OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).

RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.

RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.

CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

Original language	English
Journal	Diabetes Care
ISSN	1935-5548
DOIs	https://doi.org/10.2337/dc22-1359
Publication status	E-pub ahead of print - 3 Mar 2023

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@article{e36f8f598dc24f27bb083cc3f22b02d5,

title = "Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study",

abstract = "OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.",

author = "Thorsen, {Steffen U} and Xiang Liu and Yachana Kataria and Thomas Mandrup-Poulsen and Simranjeet Kaur and Ulla Uusitalo and Virtanen, {Suvi M} and Norris, {Jill M} and Marian Rewers and William Hagopian and Jimin Yang and Jin-Xiong She and Beena Akolkar and Stephen Rich and Aronsson, {Carin Andr{\'e}n} and {\AA}ke Lernmark and Anette-Gabriele Ziegler and Jorma Toppari and Jeffrey Krischer and Parikh, {Hemang M} and Christina Ellervik and Jannet Svensson and {Environmental Determinants of Diabetes in the Young (TEDDY) Group}",

note = "{\textcopyright} 2023 by the American Diabetes Association.",

year = "2023",

month = mar,

day = "3",

doi = "10.2337/dc22-1359",

language = "English",

journal = "Diabetes Care",

issn = "1935-5548",

publisher = "American Diabetes Association",

}

TY - JOUR

T1 - Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload

T2 - Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study

AU - Thorsen, Steffen U

AU - Liu, Xiang

AU - Kataria, Yachana

AU - Mandrup-Poulsen, Thomas

AU - Kaur, Simranjeet

AU - Uusitalo, Ulla

AU - Virtanen, Suvi M

AU - Norris, Jill M

AU - Rewers, Marian

AU - Hagopian, William

AU - Yang, Jimin

AU - She, Jin-Xiong

AU - Akolkar, Beena

AU - Rich, Stephen

AU - Aronsson, Carin Andrén

AU - Lernmark, Åke

AU - Ziegler, Anette-Gabriele

AU - Toppari, Jorma

AU - Krischer, Jeffrey

AU - Parikh, Hemang M

AU - Ellervik, Christina

AU - Svensson, Jannet

AU - Environmental Determinants of Diabetes in the Young (TEDDY) Group

PY - 2023/3/3

Y1 - 2023/3/3

N2 - OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

AB - OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

UR - http://www.scopus.com/inward/record.url?scp=85159499696&partnerID=8YFLogxK

U2 - 10.2337/dc22-1359

DO - 10.2337/dc22-1359

M3 - Journal article

C2 - 36867433

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

ER -

Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study

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