Abstract
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 g-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.
| Original language | English |
|---|---|
| Pages (from-to) | 465-476 |
| Number of pages | 12 |
| Journal | Diabetes |
| Volume | 69 |
| Issue number | 3 |
| DOIs | |
| State | Published - 1 Mar 2020 |
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In: Diabetes, Vol. 69, No. 3, 01.03.2020, p. 465-476.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study
AU - Li, Qian
AU - Parikh, Hemang
AU - Butterworth, Martha D.
AU - Lernmark, Åke
AU - Hagopian, William
AU - Rewers, Marian
AU - She, Jin Xiong
AU - Toppari, Jorma
AU - Ziegler, Anette G.
AU - Akolkar, Beena
AU - Fiehn, Oliver
AU - Fan, Sili
AU - Krischer, Jeffrey P.
AU - Barbour, Aaron
AU - Bautista, Kimberly
AU - Baxter, Judith
AU - Felipe-Morales, Daniel
AU - Driscoll, Kimberly
AU - Frohnert, Brigitte I.
AU - Stahl, Marisa
AU - Gesualdo, Patricia
AU - Hoffman, Michelle
AU - Karban, Rachel
AU - Liu, Edwin
AU - Norris, Jill
AU - Peacock, Stesha
AU - Shorrosh, Hanan
AU - Steck, Andrea
AU - Stern, Megan
AU - Villegas, Erica
AU - Waugh, Kathleen
AU - Toppari, Jorma
AU - Simell, Olli G.
AU - Adamsson, Annika
AU - Ahonen, Suvi
AU - Åkerlund, Mari
AU - Hakola, Leena
AU - Hekkala, Anne
AU - Holappa, Henna
AU - Hyöty, Heikki
AU - Ikonen, Anni
AU - Ilonen, Jorma
AU - Jäminki, Sinikka
AU - Jokipuu, Sanna
AU - Karlsson, Leena
AU - Kero, Jukka
AU - Kähönen, Miia
AU - Knip, Mikael
AU - Koivikko, Minna Liisa
AU - Koskinen, Merja
AU - Koreasalo, Mirva
AU - Kurppa, Kalle
AU - Kytölä, Jarita
AU - Latva-Aho, Tiina
AU - Lindfors, Katri
AU - Lönnrot, Maria
AU - Mäntymäki, Elina
AU - Mattila, Markus
AU - Miettinen, Maija
AU - Multasuo, Katja
AU - Mykkänen, Teija
AU - Niininen, Tiina
AU - Niinistö, Sari
AU - Nyblom, Mia
AU - Oikarinen, Sami
AU - Ollikainen, Paula
AU - Othmani, Zhian
AU - Pohjola, Sirpa
AU - Rajala, Petra
AU - Rautanen, Jenna
AU - Riikonen, Anne
AU - Riski, Eija
AU - Pekkola, Miia
AU - Romo, Minna
AU - Ruohonen, Satu
AU - Simell, Satu
AU - Sjöberg, Maija
AU - Stenius, Aino
AU - Tossavainen, Päivi
AU - Vähä-Mäkilä, Mari
AU - Vainionpää, Sini
AU - Varjonen, Eeva
AU - Veijola, Riitta
AU - Viinikangas, Irene
AU - Virtanen, Suvi M.
AU - She, Jin Xiong
AU - Schatz, Desmond
AU - Hopkins, Diane
AU - Steed, Leigh
AU - Bryant, Jennifer
AU - Silvis, Katherine
AU - Haller, Michael
AU - Gardiner, Melissa
AU - McIndoe, Richard
AU - Sharma, Ashok
AU - Anderson, Stephen W.
AU - Jacobsen, Laura
AU - Marks, John
AU - Towe, P. D.
AU - Bonifacio, Ezio
AU - Gavrisan, Anita
AU - Gezginci, Cigdem
AU - Heublein, Anja
AU - Hoffmann, Verena
AU - Hummel, Sandra
AU - Keimer, Andrea
AU - Knopff, Annette
AU - Koch, Charlotte
AU - Koletzko, Sibylle
AU - Ramminger, Claudia
AU - Roth, Roswith
AU - Scholz, Marlon
AU - Stock, Joanna
AU - Warncke, Katharina
AU - Wendel, Lorena
AU - Winkler, Christiane
AU - Agardh, Daniel
AU - Aronsson, Carin Andrén
AU - Ask, Maria
AU - Bennet, Rasmus
AU - Cilio, Corrado
AU - Engqvist, Helene
AU - Ericson-Hallström, Emelie
AU - Fors, Annika
AU - Fransson, Lina
AU - Gard, Thomas
AU - Hansen, Monika
AU - Jisser, Hanna
AU - Johansen, Fredrik
AU - Jonsdottir, Berglind
AU - Jovic, Silvija
AU - Larsson, Helena Elding
AU - Lindström, Marielle
AU - Lundgren, Markus
AU - Maziarz, Marlena
AU - Månsson-Martinez, Maria
AU - Markan, Maria
AU - Melin, Jessica
AU - Mestan, Zeliha
AU - Nilsson, Caroline
AU - Ottosson, Karin
AU - Rahmati, Kobra
AU - Ramelius, Anita
AU - Salami, Falastin
AU - Sjöberg, Anette
AU - Sjöberg, Birgitta
AU - Svensson, Malin
AU - Törn, Carina
AU - Wallin, Anne
AU - Wimar, Åsa
AU - Åberg, Sofie
AU - Hagopian, William A.
AU - Killian, Michael
AU - Crouch, Claire Cowen
AU - Skidmore, Jennifer
AU - Chavoshi, Masumeh
AU - Hervey, Rachel
AU - Lyons, Rachel
AU - Meyer, Arlene
AU - Mulenga, Denise
AU - Radtke, Jared
AU - Romancik, Matei
AU - Schmitt, Davey
AU - Zink, Sarah
AU - Becker, Dorothy
AU - Franciscus, Margaret
AU - Smith, Mary Ellen Dalmagro Elias
AU - Daftary, Ashi
AU - Klein, Mary Beth
AU - Yates, Chrystal
AU - Krischer, Jeffrey P.
AU - Austin-Gonzalez, Sarah
AU - Avendano, Maryouri
AU - Baethke, Sandra
AU - Brown, Rasheedah
AU - Burkhardt, Brant
AU - Butterworth, Martha
AU - Clasen, Joanna
AU - Cuthbertson, David
AU - Dankyi, Stephen
AU - Eberhard, Christopher
AU - Fiske, Steven
AU - Garmeson, Jennifer
AU - Gowda, Veena
AU - Heyman, Kathleen
AU - Hsiao, Belinda
AU - Karges, Christina
AU - Laras, Francisco Perez
AU - Lee, Hye Seung
AU - Li, Qian
AU - Liu, Shu
AU - Liu, Xiang
AU - Lynch, Kristian
AU - Maguire, Colleen
AU - Malloy, Jamie
AU - McCarthy, Cristina
AU - Merrell, Aubrie
AU - Parikh, Hemang
AU - Quigley, Ryan
AU - Remedios, Cassandra
AU - Shaffer, Chris
AU - Smith, Laura
AU - Smith, Susan
AU - Sulman, Noah
AU - Tamura, Roy
AU - Tewey, Dena
AU - Toth, Michael
AU - Uusitalo, Ulla
AU - Vehik, Kendra
AU - Vijayakandipan, Ponni
AU - Wood, Keith
AU - Yang, Jimin
AU - Abbondondolo, Michael
AU - Ballard, Lori
AU - Hadley, David
AU - McLeod, Wendy
AU - Meulemans, Steven
AU - Akolkar, Beena
AU - Bourcier, Kasia
AU - Briese, Thomas
AU - Johnson, Suzanne Bennett
AU - Triplett, Eric
AU - Yu, Liping
AU - Miao, Dongmei
AU - Bingley, Polly
AU - Williams, Alistair
AU - Chandler, Kyla
AU - Ball, Olivia
AU - Kelland, Ilana
AU - Grace, Sian
AU - Erlich, Henry
AU - Mack, Steven J.
AU - Fear, Anna Lisa
AU - Fiehn, Oliver
AU - Wikoff, Bill
AU - Defelice, Brian
AU - Grapov, Dmitry
AU - Kind, Tobias
AU - Palazoglu, Mine
AU - Valdiviez, Luis
AU - Wancewicz, Benjamin
AU - Wohlgemuth, Gert
AU - Wong, Joyce
AU - Rich, Stephen S.
AU - Chen, Wei Min
AU - Onengut-Gumuscu, Suna
AU - Farber, Emily
AU - Pickin, Rebecca Roche
AU - Davis, Jonathan
AU - Davis, Jordan
AU - Gallo, Dan
AU - Bonnie, Jessica
AU - Campolieto, Paul
N1 - Publisher Copyright: © 2020 by the American Diabetes Association.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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 g-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.
AB - 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 g-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.
UR - https://www.scopus.com/pages/publications/85081143063
U2 - 10.2337/db19-0756
DO - 10.2337/db19-0756
M3 - Article
C2 - 32029481
AN - SCOPUS:85081143063
SN - 0012-1797
VL - 69
SP - 465
EP - 476
JO - Diabetes
JF - Diabetes
IS - 3
ER -