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

Steffen U Thorsen; Xiang Liu; Yachana Kataria; Thomas Mandrup-Poulsen; Simranjeet Kaur; Ulla Uusitalo; Suvi M Virtanen; Jill M Norris; Marian Rewers; William Hagopian; Jimin Yang; Jin-Xiong She; Beena Akolkar; Stephen Rich; Carin Andrén Aronsson; Åke Lernmark; Anette-Gabriele Ziegler; Jorma Toppari; Jeffrey Krischer; Hemang M Parikh; Christina Ellervik; Jannet Svensson; 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

Steffen U Thorsen, Xiang Liu, Yachana Kataria, Thomas Mandrup-Poulsen, Simranjeet Kaur, Ulla Uusitalo, Suvi M Virtanen, Jill M Norris, Marian Rewers, William Hagopian, Jimin Yang, Jin-Xiong She, Beena Akolkar, Stephen Rich, Carin Andrén Aronsson, Åke Lernmark, Anette-Gabriele Ziegler, Jorma Toppari, Jeffrey Krischer, Hemang M ParikhChristina Ellervik, Jannet Svensson, Environmental Determinants of Diabetes in the Young (TEDDY) Group

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

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
Pages (from-to)	1014-1018
Journal	Diabetes Care
Volume	46
Issue number	5
Early online date	2023 Mar 3
DOIs	https://doi.org/10.2337/dc22-1359
Publication status	Published - 2023

Subject classification (UKÄ)

Endocrinology and Diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/dc22-1359

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Thorsen, S. U., Liu, X., Kataria, Y., Mandrup-Poulsen, T., Kaur, S., Uusitalo, U., Virtanen, S. M., Norris, J. M., Rewers, M., Hagopian, W., Yang, J., She, J.-X., Akolkar, B., Rich, S., Aronsson, C. A., Lernmark, Å., Ziegler, A.-G., Toppari, J., Krischer, J., ... Environmental Determinants of Diabetes in the Young (TEDDY) Group (2023). Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study. Diabetes Care, 46(5), 1014-1018. https://doi.org/10.2337/dc22-1359

@article{9a78c4f2aa9c48d2b601ab8b2baf0948,

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",

doi = "10.2337/dc22-1359",

language = "English",

volume = "46",

pages = "1014--1018",

journal = "Diabetes Care",

issn = "1935-5548",

publisher = "American Diabetes Association",

number = "5",

}

Thorsen, SU, Liu, X, Kataria, Y, Mandrup-Poulsen, T, Kaur, S, Uusitalo, U, Virtanen, SM, Norris, JM, Rewers, M, Hagopian, W, Yang, J, She, J-X, Akolkar, B, Rich, S, Aronsson, CA , Lernmark, Å, Ziegler, A-G, Toppari, J, Krischer, J, Parikh, HM, Ellervik, C, Svensson, J & Environmental Determinants of Diabetes in the Young (TEDDY) Group 2023, 'Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study', Diabetes Care, vol. 46, no. 5, pp. 1014-1018. https://doi.org/10.2337/dc22-1359

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

Y1 - 2023

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.

U2 - 10.2337/dc22-1359

DO - 10.2337/dc22-1359

M3 - Article

C2 - 36867433

SN - 1935-5548

VL - 46

SP - 1014

EP - 1018

JO - Diabetes Care

JF - Diabetes Care

IS - 5

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

Abstract

Subject classification (UKÄ)

UN SDGs

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