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

被引：4

作者：

Thorsen, Steffen U. ^{[1
,2
]}

Liu, Xiang ^{[3
]}

Kataria, Yachana ^{[4
]}

Mandrup-Poulsen, Thomas ^{[1
]}

Kaur, Simranjeet ^{[2
]}

Uusitalo, Ulla ^{[3
]}

Virtanen, Suvi M. ^{[5
,6
,7
,8
]}

Norris, Jill M. ^{[9
]}

Rewers, Marian ^{[10
]}

Hagopian, William ^{[11
]}

Yang, Jimin ^{[12
]}

She, Jin-Xiong ^{[12
]}

Akolkar, Beena ^{[13
]}

Rich, Stephen ^{[14
,15
]}

Aronsson, Carin Andren ^{[16
]}

Lernmark, Ake ^{[16
]}

Ziegler, Anette-Gabriele ^{[17
,18
,19
]}

Toppari, Jorma ^{[20
,21
,22
]}

Krischer, Jeffrey ^{[3
]}

Parikh, Hemang M. ^{[3
]}

Ellervik, Christina ^{[23
,24
,25
]}

Svensson, Jannet ^{[2
,23
]}

机构：

[1] Univ Copenhagen, Dept Biomed Sci, Copenhagen, Denmark

[2] Copenhagen Univ Hosp, Steno Diabet Ctr Copenhagen, Herlev, Denmark

[3] Univ S Florida, Hlth Informat Inst, Morsani Coll Med, Tampa, FL USA

[4] Boston Univ, Dept Pathol & Lab Med, Boston, MA 02215 USA

[5] Finnish Inst Hlth & Welf, Dept Publ Hlth & Welf, Helsinki, Finland

[6] Tampere Univ, Unit Hlth Sci, Fac Social Sci, Tampere, Finland

[7] Tampere Univ, Ctr Child Hlth Res, Tampere, Finland

[8] Tampere Univ Hosp, Univ Hosp & Res, Dev & Innovat Ctr, Tampere, Finland

[9] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA

[10] Pacific Northwest Res Inst, 720 Broadway, Seattle, WA 98122 USA

[11] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA

[12] Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA

[13] NIDDK, Bethesda, MD 20892 USA

[14] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[15] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA

[16] Lund Univ, Clin Res Ctr, Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden

[17] Helmholtz Zentrum Munchen, Inst Diabet Res, Neuherberg, Germany

[18] Tech Univ Munich, Klinikum Rechts Isar, Munich, Germany

[19] Forschergrp Diabet eV, Neuherberg, Germany

[20] Univ Turku, Res Ctr Integrat Physiol & Pharmacol, Inst Biomed, Turku, Finland

[21] Univ Turku, Ctr Populat Hlth Res, Turku, Finland

[22] Turku Univ Hosp, Dept Pediat, Turku, Finland

[23] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark

[24] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA

[25] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA

来源：

DIABETES CARE | 2023年 / 46卷 / 05期

基金：

美国国家卫生研究院;

关键词：

ENVIRONMENTAL DETERMINANTS; AUTOANTIBODIES;

D O I：

10.2337/dc22-1359

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVETo 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 METHODSIn 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. RESULTSWe found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS & GE;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. CONCLUSIONSIron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

引用

页码：1014 / 1018

页数：6

共 19 条

[1] Iron Regulation of Pancreatic Beta-Cell Functions and Oxidative Stress [J].

Backe, Marie Balslev ;

Moen, Ingrid Wahl ;

Ellervik, Christina ;

Hansen, Jakob Bondo ;

Mandrup-Poulsen, Thomas .

ANNUAL REVIEW OF NUTRITION, VOL 36, 2016, 36 :241-273

[2] Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis [J].

Benyamin, Beben ;

Esko, Tonu ;

Ried, Janina S. ;

Radhakrishnan, Aparna ;

Vermeulen, Sita H. ;

Traglia, Michela ;

Goegele, Martin ;

Anderson, Denise ;

Broer, Linda ;

Podmore, Clara ;

Luan, Jian'an ;

Kutalik, Zoltan ;

Sanna, Serena ;

van der Meer, Peter ;

Tanaka, Toshiko ;

Wang, Fudi ;

Westra, Harm-Jan ;

Franke, Lude ;

Mihailov, Evelin ;

Milani, Lili ;

Haeldin, Jonas ;

Winkelmann, Juliane ;

Meitinger, Thomas ;

Thiery, Joachim ;

Peters, Annette ;

Waldenberger, Melanie ;

Rendon, Augusto ;

Jolley, Jennifer ;

Sambrook, Jennifer ;

Kiemeney, Lambertus A. ;

Sweep, Fred C. ;

Sala, Cinzia F. ;

Schwienbacher, Christine ;

Pichler, Irene ;

Hui, Jennie ;

Demirkan, Ayse ;

Isaacs, Aaron ;

Amin, Najaf ;

Steri, Maristella ;

Waeber, Gerard ;

Verweij, Niek ;

Powell, Joseph E. ;

Nyholt, Dale R. ;

Heath, Andrew C. ;

Madden, Pamela A. F. ;

Visscher, Peter M. ;

Wright, Margaret J. ;

Montgomery, Grant W. ;

Martin, Nicholas G. ;

Hernandez, Dena .

NATURE COMMUNICATIONS, 2014, 5

[3] Common variants in TMPRSS6 are associated with iron status and erythrocyte volume [J].

Benyamin, Beben ;

Ferreira, Manuel A. R. ;

Willemsen, Gonneke ;

Gordon, Scott ;

Middelberg, Rita P. S. ;

McEvoy, Brian P. ;

Hottenga, Jouke-Jan ;

Henders, Anjali K. ;

Campbell, Megan J. ;

Wallace, Leanne ;

Frazer, Ian H. ;

Heath, Andrew C. ;

de Geus, Eco J. C. ;

Nyholt, Dale R. ;

Visscher, Peter M. ;

Penninx, Brenda W. ;

Boomsma, Dorret I. ;

Martin, Nicholas G. ;

Montgomery, Grant W. ;

Whitfield, John B. .

NATURE GENETICS, 2009, 41 (11) :1173-1175

[4] Iron induced RNA-oxidation in the general population and in mouse tissue [J].

Cejvanovic, Vanja ;

Kjaer, Laura Kofoed ;

Bergholdt, Helle Kirstine Morup ;

Torp-Pedersen, Arendse ;

Henriksen, Trine ;

Weimann, Allan ;

Ellervik, Christina ;

Poulsen, Henrik Enghusen .

FREE RADICAL BIOLOGY AND MEDICINE, 2018, 115 :127-135

[5] The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants [J].

Hagopian, William A. ;

Erlich, Henry ;

Lernmark, Ake ;

Rewers, Marian ;

Ziegler, Anette G. ;

Simell, Olli ;

Akolkar, Beena ;

Vogt, Robert, Jr. ;

Blair, Alan ;

Ilonen, Jorma ;

Krischer, Jeffrey ;

She, JinXiong .

PEDIATRIC DIABETES, 2011, 12 (08) :733-743

[6]

Krischer J, 2007, PEDIATR DIABETES, V8, P286

[7] The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study [J].

Krischer, Jeffrey P. ;

Lynch, Kristian F. ;

Schatz, Desmond A. ;

Ilonen, Jorma ;

Lernmark, Ake ;

Hagopian, William A. ;

Rewers, Marian J. ;

She, Jin-Xiong ;

Simell, Olli G. ;

Toppari, Jorma ;

Ziegler, Anette-G. ;

Akolkar, Beena ;

Bonifacio, Ezio .

DIABETOLOGIA, 2015, 58 (05) :980-987

[8] High Neonatal Blood Iron Content Is Associated with the Risk of Childhood Type 1 Diabetes Mellitus [J].

Kyvsgaard, Julie Nyholm ;

Overgaard, Anne Julie ;

Thorsen, Steffen Ullitz ;

Hansen, Thomas Hesselhoj ;

Pipper, Christian Bressen ;

Mortensen, Henrik Bindesbol ;

Pociot, Flemming ;

Svensson, Jannet .

NUTRIENTS, 2017, 9 (11)

[9] Neoepitopes: a new take on beta cell autoimmunity in type 1 diabetes [J].

Mannering, Stuart I. ;

Di Carluccio, Anthony R. ;

Elso, Colleen M. .

DIABETOLOGIA, 2019, 62 (03) :351-356

[10] Iron in infection and immunity [J].

Nairz, Manfred ;

Weiss, Guenter .

MOLECULAR ASPECTS OF MEDICINE, 2020, 75

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