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

The TEDDY Study Group.; 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 Andren Aronsson; Åke Lernmark; Anette Gabriele Ziegler; Jorma Toppari; Jeffrey Krischer; Hemang M. Parikh; Christina Ellervik; Jannet Svensson

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

The TEDDY Study Group.
, 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 Andren Aronsson
, Åke Lernmark
, Anette Gabriele Ziegler
, Jorma Toppari
, Jeffrey Krischer

Hemang M. Parikh, Christina Ellervik, Jannet Svensson^*

^*Corresponding author for this work

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

5 Citations (Scopus)

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
Number of pages	5
Journal	DIABETES CARE
Volume	46
Issue number	5
DOIs	https://doi.org/10.2337/dc22-1359
Publication status	Published - 2023
Publication type	A1 Journal article-refereed

Funding

Funding. The TEDDY study is funded by grants U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, and U01 DK128847 and contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, Centers for Disease Control and Prevention, and JDRF. This work is supported in part by the National Institutes of Health/National Center for Advancing Translational sciences clinical and translational science awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535) and by Fabrikant Vilhelm Pedersen og Hustrus Mindelegat grant 17798.

Keywords

Child
Humans
Infant
Diabetes Mellitus, Type 1
Autoimmunity/genetics
Iron, Dietary
Iron
Islets of Langerhans
Risk Factors
Autoantibodies/genetics
Iron Overload/genetics
Genetic Predisposition to Disease

Publication forum classification

Publication forum level 3

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Advanced and Specialised Nursing

UN SDGs

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

Access to Document

10.2337/dc22-1359

Cite this

The TEDDY Study Group., 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., ... Svensson, J. (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{a2e6955cd5a8406bba68803992f42045,

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.",

keywords = "Child, Humans, Infant, Diabetes Mellitus, Type 1, Autoimmunity/genetics, Iron, Dietary, Iron, Islets of Langerhans, Risk Factors, Autoantibodies/genetics, Iron Overload/genetics, Genetic Predisposition to Disease",

author = "\{The TEDDY Study Group.\} and 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 She, \{Jin Xiong\} and Beena Akolkar and Stephen Rich and Aronsson, \{Carin Andren\} and {\AA}ke Lernmark and Ziegler, \{Anette Gabriele\} and Jorma Toppari and Jeffrey Krischer and Parikh, \{Hemang M.\} and Christina Ellervik and Jannet Svensson",

note = "Funding Information: Funding. The TEDDY study is funded by grants U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, and U01 DK128847 and contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, Centers for Disease Control and Prevention, and JDRF. This work is supported in part by the National Institutes of Health/National Center for Advancing Translational sciences clinical and translational science awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535) and by Fabrikant Vilhelm Pedersen og Hustrus Mindelegat grant 17798. Publisher Copyright: {\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 = "0149-5992",

publisher = "American Diabetes Association",

number = "5",

}

The TEDDY Study Group., Thorsen, SU, Liu, X, Kataria, Y, Mandrup-Poulsen, T, Kaur, S, Uusitalo, U, Virtanen, SM, Norris, JM, Rewers, M, Hagopian, W, Yang, J, She, JX, Akolkar, B, Rich, S, Aronsson, CA, Lernmark, Å, Ziegler, AG, Toppari, J, Krischer, J, Parikh, HM, Ellervik, C & Svensson, J 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 - The TEDDY Study Group.

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 Andren

AU - Lernmark, Åke

AU - Ziegler, Anette Gabriele

AU - Toppari, Jorma

AU - Krischer, Jeffrey

AU - Parikh, Hemang M.

AU - Ellervik, Christina

AU - Svensson, Jannet

N1 - Funding Information: Funding. The TEDDY study is funded by grants U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, and U01 DK128847 and contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, Centers for Disease Control and Prevention, and JDRF. This work is supported in part by the National Institutes of Health/National Center for Advancing Translational sciences clinical and translational science awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535) and by Fabrikant Vilhelm Pedersen og Hustrus Mindelegat grant 17798. Publisher Copyright: © 2023 by the American Diabetes Association.

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.

KW - Child

KW - Humans

KW - Infant

KW - Diabetes Mellitus, Type 1

KW - Autoimmunity/genetics

KW - Iron, Dietary

KW - Iron

KW - Islets of Langerhans

KW - Risk Factors

KW - Autoantibodies/genetics

KW - Iron Overload/genetics

KW - Genetic Predisposition to Disease

U2 - 10.2337/dc22-1359

DO - 10.2337/dc22-1359

M3 - Article

C2 - 36867433

AN - SCOPUS:85159499696

SN - 0149-5992

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

Funding

Keywords

Publication forum classification

ASJC Scopus subject areas

UN SDGs

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