Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study | Zendy

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Open Access

Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study

Author(s) -

Qian Li,

Hemang Parikh,

Martha Butterworth,

Åke Lernmark,

William Hagopian,

Marian Rewers,

JinXiong She,

Jorma Toppari,

AnetteG. Ziegler,

Beena Akolkar,

Oliver Fiehn,

Sili Fan,

Jeffrey P. Krischer,

Aaron Barbour,

Kimberly Bautista,

Judith Baxter,

Daniel Felipe-Morales,

Kimberly A. Driscoll,

Brigitte I. Frohnert,

Marisa Stahl,

Patricia Gesualdo,

Michelle Hoffman,

Rachel Karban,

Edwin Liu,

Jill M. Norris,

Stesha Peacock,

Hanan Shorrosh,

Andrea K. Steck,

Megan Stern,

Erica Villegas,

Kathleen Waugh,

Olli Simell,

Annika Adamsson,

Suvi Ahonen,

Iris Erlund,

Leena Hakola,

Anne Hekkala,

Henna Holappa,

Heikki Hyöty,

Anni Ikonen,

Jorma Ilonen,

Sinikka Jäminki,

Sanna Jokipuu,

Leena Eklund Karlsson,

Jukka Kero,

Miia Kähönen,

Mikael Knip,

Minna-Liisa Koivikko,

Merja Koskinen,

Mirva Koreasalo,

Kalle Kurppa,

Jarita Kytölä,

Tiina Latva-aho,

Katri Lindfors,

Maria Lönnrot,

Elina Mäntymäki,

Markus Mattila,

Maija E. Miettinen,

Katja Multasuo,

Teija Mykkänen,

Tiiiininen,

Sari Niinistö,

Mia Nyblom,

Sami Oikarinen,

Paula Ollikainen,

Zhian Othmani,

Sirpa Pohjola,

Petra Rajala,

Jenna Rautanen,

Anne Riikonen,

Eija Riski,

Miia Pekkola,

Minna Romo,

Satu Ruohonen,

Satu Simell,

Maija Sjöberg,

Aino Stenius,

Päivi Tossavainen,

Mari Vähä-Mäkilä,

Sini Vainionpää,

Eeva Varjonen,

Riitta Veijola,

Irene Viinikangas,

Suvi Μ. Virtanen,

Desmond Schatz,

Diane Hopkins,

Leigh Steed,

Jennifer Bryant,

Katherine Silvis,

Michael J. Haller,

Melissa Gardiner,

Richard McIndoe,

Ashok Sharma,

Stephen W. Anderson,

Laura M. Jacobsen,

John Marks,

P.D. Towe,

Anette G. Ziegler,

Ezio Bonifacio,

Anita Gavrisan,

Cigdem Gezginci,

Anja Heublein,

Verena Hoffmann,

Sandra Hummel,

Andrea Keimer,

Annette Knopff,

Charlotte Koch,

Sibylle Koletzko,

Claudia Ramminger,

Roswith Roth,

Marlon Scholz,

Joanna Stock,

Katharina Warncke,

Lorena Wendel,

Christiane Winkler,

Daniel Agardh,

Carin Andrén Aronsson,

Maria Ask,

Rasmus Bennet,

Corrado Cilio,

Helene Engqvist,

Emelie Ericson-Hallström,

Annika Fors,

Lina Fransson,

Thomas Gard,

Monika Hansen,

Hanna Jisser,

Fredrik Johansen,

Berglind Jónsdóttir,

Silvija Jović,

Helena Elding Larsson,

Marielle Lindström,

Markus Lundgren,

Marlena Maziarz,

Maria Månsson-Martinez,

Maria Markan,

Jessica Melin,

Zeliha Mestan,

Caroline Nilsson,

Karin Ottosson,

Kobra Rahmati,

Anita Ramelius,

Falastin Salami,

Anette Sjöberg,

Birgitta Janerot-Sjöberg,

Malin Svensson,

Carina Törn,

Anne Wallin,

Åsa Wimar,

Sofie Åberg,

Michael Killian,

Claire Cowen Crouch,

Jennifer Skidmore,

Masumeh Chavoshi,

Rachel Hervey,

Rachel Lyons,

Arlene Meyer,

Denise Mulenga,

Jared Radtke,

Matei Romancik,

Davey Schmitt,

Sarah Zink,

Dorothy Becker,

Margaret Franciscus,

MaryEllen Dalmagro-Elias Smith,

Ashi Daftary,

Mary Beth Klein,

Chrystal Yates,

Sarah Austin-Gonzalez,

Maryouri Avendano,

Sandra Baethke,

Rasheedah Brown,

Brant Burkhardt,

Joanna Clasen,

David Cuthbertson,

Stephen Dankyi,

Christopher Eberhard,

Steven Fiske,

Jennifer Garmeson,

Veena Gowda,

Kathleen Heyman,

Belinda Hsiao,

Christina Karges,

Francisco Perez Laras,

HyeSeung Lee,

Shu Liu,

Xiang Liu,

Kristian Lynch,

Colleen Maguire,

Jamie Malloy,

Cristina McCarthy,

Aubrie Merrell,

Ryan Quigley,

Cassandra Remedios,

Chris Shaffer,

Laura Smith,

Susan Smith,

Noah Sulman,

Roy Tamura,

Dena Tewey,

Michael J. Toth,

Ulla Uusitalo,

Kendra Vehik,

Ponni Vijayakandipan,

Keith Wood,

Jimin Yang,

Michael Abbondondolo,

Lori Ballard,

David Hadley,

Wendy McLeod,

Steven Meulemans,

Kasia Bourcier,

Thomas Briese,

Suzanne Bennett Johnson,

Eric W. Triplett,

Liping Yu Dongmei Miao,

Polly J. Bingley,

Alistair J.K. Williams,

Kyla Chandler,

Olivia Ball,

Ilana Kelland,

Sian Grace,

M Kellis,

Steven J. Mack,

Anna Lisa Fear,

Bill Wikoff,

Brian C. DeFelice,

Dmitry Grapov,

Tobias Kind,

Mine Palazoglu,

Luis Valdiviez,

Benjamin Wancewicz,

Gert Wohlgemuth,

Joyce Wong,

Stephen S. Rich,

WeiMin Chen,

Suna Önengüt-Gümüşcü,

Emily Farber,

Rebecca Roche Pickin,

Jonathan M. Davis,

Jordan Davis,

Dan Gallo,

Jessica Bonnie,

Paul Campolieto

Publication year - 2020

Publication title -

diabetes

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.219

H-Index - 330

eISSN - 1939-327X

pISSN - 0012-1797

DOI - 10.2337/db19-0756

Subject(s) - metabolome , amino acid , autoantibody , methionine , type 1 diabetes , islet , medicine , endocrinology , insulin , biochemistry , biology , diabetes mellitus , chemistry , metabolite , antibody , immunology

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children’s plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and γ-aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.

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