Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study

Qian Li; Hemang Parikh; Martha D. Butterworth; Åke Lernmark; William Hagopian; Marian Rewers; Jin Xiong She; Jorma Toppari; Anette G. Ziegler; Beena Akolkar; Oliver Fiehn; Sili Fan; Jeffrey P. Krischer; Marian Rewers; Aaron Barbour; Kimberly Bautista; Judith Baxter; Daniel Felipe-Morales; Kimberly Driscoll; Brigitte I. Frohnert; Marisa Stahl; Patricia Gesualdo; Michelle Hoffman; Rachel Karban; Edwin Liu; Jill Norris; Stesha Peacock; Hanan Shorrosh; Andrea Steck; Megan Stern; Erica Villegas; Kathleen Waugh; Jorma Toppari; Olli G. Simell; Annika Adamsson; Suvi Ahonen; Mari Åkerlund; Leena Hakola; Anne Hekkala; Henna Holappa; Heikki Hyöty; Anni Ikonen; Jorma Ilonen; Sinikka Jäminki; Sanna Jokipuu; Leena 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 Miettinen; Katja Multasuo; Teija Mykkänen; Tiina Niininen; 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 M. Virtanen; Jin Xiong She; Desmond Schatz; Diane Hopkins; Leigh Steed; Jennifer Bryant; Katherine Silvis; Michael Haller; Melissa Gardiner; Richard McIndoe; Ashok Sharma; Stephen W. Anderson; Laura 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; Åke Lernmark; 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 Jonsdottir; Silvija Jovic; 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 Sjöberg; Malin Svensson; Carina Törn; Anne Wallin; Åsa Wimar; Sofie Åberg; William A. Hagopian; 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; Mary Ellen Dalmagro Elias Smith; Ashi Daftary; Mary Beth Klein; Chrystal Yates; Jeffrey P. Krischer; Sarah Austin-Gonzalez; Maryouri Avendano; Sandra Baethke; Rasheedah Brown; Brant Burkhardt; Martha Butterworth; Joanna Clasen; David Cuthbertson; Stephen Dankyi; Christopher Eberhard; Steven Fiske; Jennifer Garmeson; Veena Gowda; Kathleen Heyman; Belinda Hsiao; Christina Karges; Francisco Perez Laras; Hye Seung Lee; Qian Li; Shu Liu; Xiang Liu; Kristian Lynch; Colleen Maguire; Jamie Malloy; Cristina McCarthy; Aubrie Merrell; Hemang Parikh; Ryan Quigley; Cassandra Remedios; Chris Shaffer; Laura Smith; Susan Smith; Noah Sulman; Roy Tamura; Dena Tewey; Michael Toth; Ulla Uusitalo; Kendra Vehik; Ponni Vijayakandipan; Keith Wood; Jimin Yang; Michael Abbondondolo; Lori Ballard; David Hadley; Wendy McLeod; Steven Meulemans; Beena Akolkar; Kasia Bourcier; Thomas Briese; Suzanne Bennett Johnson; Eric Triplett; Liping Yu; Dongmei Miao; Polly Bingley; Alistair Williams; Kyla Chandler; Olivia Ball; Ilana Kelland; Sian Grace; Henry Erlich; Steven J. Mack; Anna Lisa Fear; Oliver Fiehn; Bill Wikoff; Brian Defelice; Dmitry Grapov; Tobias Kind; Mine Palazoglu; Luis Valdiviez; Benjamin Wancewicz; Gert Wohlgemuth; Joyce Wong; Stephen S. Rich; Wei Min Chen; Suna Onengut-Gumuscu; Emily Farber; Rebecca Roche Pickin; Jonathan Davis; Jordan Davis; Dan Gallo; Jessica Bonnie; Paul Campolieto

doi:10.2337/db19-0756

Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study

Qian Li, Hemang Parikh, Martha D. Butterworth, Åke Lernmark, William Hagopian, Marian Rewers, Jin Xiong She, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Oliver Fiehn, Sili Fan, Jeffrey P. Krischer, Marian Rewers, Aaron Barbour, Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Kimberly Driscoll, Brigitte I. FrohnertMarisa Stahl, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Stesha Peacock, Hanan Shorrosh, Andrea Steck, Megan Stern, Erica Villegas, Kathleen Waugh, Jorma Toppari, Olli G. Simell, Annika Adamsson, Suvi Ahonen, Mari Åkerlund, Leena Hakola, Anne Hekkala, Henna Holappa, Heikki Hyöty, Anni Ikonen, Jorma Ilonen, Sinikka Jäminki, Sanna Jokipuu, Leena 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 Miettinen, Katja Multasuo, Teija Mykkänen, Tiina Niininen, 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 M. Virtanen, Jin Xiong She, Desmond Schatz, Diane Hopkins, Leigh Steed, Jennifer Bryant, Katherine Silvis, Michael Haller, Melissa Gardiner, Richard McIndoe, Ashok Sharma, Stephen W. Anderson, Laura 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, Åke Lernmark, 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 Jonsdottir, Silvija Jovic, 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 Sjöberg, Malin Svensson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A. Hagopian, 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, Mary Ellen Dalmagro Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Jeffrey P. Krischer, Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, Joanna Clasen, David Cuthbertson, Stephen Dankyi, Christopher Eberhard, Steven Fiske, Jennifer Garmeson, Veena Gowda, Kathleen Heyman, Belinda Hsiao, Christina Karges, Francisco Perez Laras, Hye Seung Lee, Qian Li, Shu Liu, Xiang Liu, Kristian Lynch, Colleen Maguire, Jamie Malloy, Cristina McCarthy, Aubrie Merrell, Hemang Parikh, Ryan Quigley, Cassandra Remedios, Chris Shaffer, Laura Smith, Susan Smith, Noah Sulman, Roy Tamura, Dena Tewey, Michael Toth, Ulla Uusitalo, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Michael Abbondondolo, Lori Ballard, David Hadley, Wendy McLeod, Steven Meulemans, Beena Akolkar, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Eric Triplett, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Olivia Ball, Ilana Kelland, Sian Grace, Henry Erlich, Steven J. Mack, Anna Lisa Fear, Oliver Fiehn, Bill Wikoff, Brian Defelice, Dmitry Grapov, Tobias Kind, Mine Palazoglu, Luis Valdiviez, Benjamin Wancewicz, Gert Wohlgemuth, Joyce Wong, Stephen S. Rich, Wei Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jonathan Davis, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto

Obstetrics and Gynecology

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

25 Scopus citations

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 (US)
Pages (from-to)	465-476
Number of pages	12
Journal	Diabetes
Volume	69
Issue number	3
DOIs	https://doi.org/10.2337/db19-0756
State	Published - Mar 1 2020

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

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

Access to Document

10.2337/db19-0756

Cite this

Li, Q., Parikh, H., Butterworth, M. D., Lernmark, Å., Hagopian, W., Rewers, M., She, J. X., Toppari, J., Ziegler, A. G., Akolkar, B., Fiehn, O., Fan, S., Krischer, J. P., Rewers, M., Barbour, A., Bautista, K., Baxter, J., Felipe-Morales, D., Driscoll, K., ... Campolieto, P. (2020). Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study. Diabetes, 69(3), 465-476. https://doi.org/10.2337/db19-0756

Li, Q, Parikh, H, Butterworth, MD, Lernmark, Å, Hagopian, W, Rewers, M, She, JX, Toppari, J, Ziegler, AG, Akolkar, B, Fiehn, O, Fan, S, Krischer, JP, Rewers, M, Barbour, A, Bautista, K, Baxter, J, Felipe-Morales, D, Driscoll, K, Frohnert, BI, Stahl, M, Gesualdo, P, Hoffman, M, Karban, R, Liu, E, Norris, J, Peacock, S, Shorrosh, H, Steck, A, Stern, M, Villegas, E, Waugh, K, Toppari, J, Simell, OG, Adamsson, A, Ahonen, S, Åkerlund, M, Hakola, L, Hekkala, A, Holappa, H, Hyöty, H, Ikonen, A, Ilonen, J, Jäminki, S, Jokipuu, S, Karlsson, L, Kero, J, Kähönen, M, Knip, M, Koivikko, ML, Koskinen, M, Koreasalo, M, Kurppa, K, Kytölä, J, Latva-Aho, T, Lindfors, K, Lönnrot, M, Mäntymäki, E, Mattila, M, Miettinen, M, Multasuo, K, Mykkänen, T, Niininen, T, Niinistö, S, Nyblom, M, Oikarinen, S, Ollikainen, P, Othmani, Z, Pohjola, S, Rajala, P, Rautanen, J, Riikonen, A, Riski, E, Pekkola, M, Romo, M, Ruohonen, S, Simell, S, Sjöberg, M, Stenius, A, Tossavainen, P, Vähä-Mäkilä, M, Vainionpää, S, Varjonen, E, Veijola, R, Viinikangas, I, Virtanen, SM, She, JX, Schatz, D, Hopkins, D, Steed, L, Bryant, J, Silvis, K, Haller, M, Gardiner, M, McIndoe, R, Sharma, A, Anderson, SW, Jacobsen, L, Marks, J, Towe, PD, Ziegler, AG, Bonifacio, E, Gavrisan, A, Gezginci, C, Heublein, A, Hoffmann, V, Hummel, S, Keimer, A, Knopff, A, Koch, C, Koletzko, S, Ramminger, C, Roth, R, Scholz, M, Stock, J, Warncke, K, Wendel, L, Winkler, C, Lernmark, Å, Agardh, D, Aronsson, CA, Ask, M, Bennet, R, Cilio, C, Engqvist, H, Ericson-Hallström, E, Fors, A, Fransson, L, Gard, T, Hansen, M, Jisser, H, Johansen, F, Jonsdottir, B, Jovic, S, Larsson, HE, Lindström, M, Lundgren, M, Maziarz, M, Månsson-Martinez, M, Markan, M, Melin, J, Mestan, Z, Nilsson, C, Ottosson, K, Rahmati, K, Ramelius, A, Salami, F, Sjöberg, A, Sjöberg, B, Svensson, M, Törn, C, Wallin, A, Wimar, Å, Åberg, S, Hagopian, WA, Killian, M, Crouch, CC, Skidmore, J, Chavoshi, M, Hervey, R, Lyons, R, Meyer, A, Mulenga, D, Radtke, J, Romancik, M, Schmitt, D, Zink, S, Becker, D, Franciscus, M, Smith, MEDE, Daftary, A, Klein, MB, Yates, C, Krischer, JP, Austin-Gonzalez, S, Avendano, M, Baethke, S, Brown, R, Burkhardt, B, Butterworth, M, Clasen, J, Cuthbertson, D, Dankyi, S, Eberhard, C, Fiske, S, Garmeson, J, Gowda, V, Heyman, K, Hsiao, B, Karges, C, Laras, FP, Lee, HS, Li, Q, Liu, S, Liu, X, Lynch, K, Maguire, C, Malloy, J, McCarthy, C, Merrell, A, Parikh, H, Quigley, R, Remedios, C, Shaffer, C, Smith, L, Smith, S, Sulman, N, Tamura, R, Tewey, D, Toth, M, Uusitalo, U, Vehik, K, Vijayakandipan, P, Wood, K, Yang, J, Abbondondolo, M, Ballard, L, Hadley, D, McLeod, W, Meulemans, S, Akolkar, B, Bourcier, K, Briese, T, Johnson, SB, Triplett, E, Yu, L, Miao, D, Bingley, P, Williams, A, Chandler, K, Ball, O, Kelland, I, Grace, S, Erlich, H, Mack, SJ, Fear, AL, Fiehn, O, Wikoff, B, Defelice, B, Grapov, D, Kind, T, Palazoglu, M, Valdiviez, L, Wancewicz, B, Wohlgemuth, G, Wong, J, Rich, SS, Chen, WM, Onengut-Gumuscu, S, Farber, E, Pickin, RR, Davis, J, Davis, J, Gallo, D, Bonnie, J & Campolieto, P 2020, 'Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study', Diabetes, vol. 69, no. 3, pp. 465-476. https://doi.org/10.2337/db19-0756

@article{c977c6139ab84597a1661712aad66b37,

title = "Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study",

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{\textquoteright}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.",

author = "Qian Li and Hemang Parikh and Butterworth, {Martha D.} and {\AA}ke Lernmark and William Hagopian and Marian Rewers and She, {Jin Xiong} and Jorma Toppari and Ziegler, {Anette G.} and Beena Akolkar and Oliver Fiehn and Sili Fan and Krischer, {Jeffrey P.} and Marian Rewers and Aaron Barbour and Kimberly Bautista and Judith Baxter and Daniel Felipe-Morales and Kimberly Driscoll and Frohnert, {Brigitte I.} and Marisa Stahl and Patricia Gesualdo and Michelle Hoffman and Rachel Karban and Edwin Liu and Jill Norris and Stesha Peacock and Hanan Shorrosh and Andrea Steck and Megan Stern and Erica Villegas and Kathleen Waugh and Jorma Toppari and Simell, {Olli G.} and Annika Adamsson and Suvi Ahonen and Mari {\AA}kerlund and Leena Hakola and Anne Hekkala and Henna Holappa and Heikki Hy{\"o}ty and Anni Ikonen and Jorma Ilonen and Sinikka J{\"a}minki and Sanna Jokipuu and Leena Karlsson and Jukka Kero and Miia K{\"a}h{\"o}nen and Mikael Knip and Koivikko, {Minna Liisa} and Merja Koskinen and Mirva Koreasalo and Kalle Kurppa and Jarita Kyt{\"o}l{\"a} and Tiina Latva-Aho and Katri Lindfors and Maria L{\"o}nnrot and Elina M{\"a}ntym{\"a}ki and Markus Mattila and Maija Miettinen and Katja Multasuo and Teija Mykk{\"a}nen and Tiina Niininen and Sari Niinist{\"o} and Mia Nyblom and Sami Oikarinen and Paula Ollikainen and Zhian Othmani and Sirpa Pohjola and Petra Rajala and Jenna Rautanen and Anne Riikonen and Eija Riski and Miia Pekkola and Minna Romo and Satu Ruohonen and Satu Simell and Maija Sj{\"o}berg and Aino Stenius and P{\"a}ivi Tossavainen and Mari V{\"a}h{\"a}-M{\"a}kil{\"a} and Sini Vainionp{\"a}{\"a} and Eeva Varjonen and Riitta Veijola and Irene Viinikangas and Virtanen, {Suvi M.} and She, {Jin Xiong} and Desmond Schatz and Diane Hopkins and Leigh Steed and Jennifer Bryant and Katherine Silvis and Michael Haller and Melissa Gardiner and Richard McIndoe and Ashok Sharma and Anderson, {Stephen W.} and Laura Jacobsen and John Marks and Towe, {P. D.} and Ziegler, {Anette G.} and Ezio Bonifacio and Anita Gavrisan and Cigdem Gezginci and Anja Heublein and Verena Hoffmann and Sandra Hummel and Andrea Keimer and Annette Knopff and Charlotte Koch and Sibylle Koletzko and Claudia Ramminger and Roswith Roth and Marlon Scholz and Joanna Stock and Katharina Warncke and Lorena Wendel and Christiane Winkler and {\AA}ke Lernmark and Daniel Agardh and Aronsson, {Carin Andr{\'e}n} and Maria Ask and Rasmus Bennet and Corrado Cilio and Helene Engqvist and Emelie Ericson-Hallstr{\"o}m and Annika Fors and Lina Fransson and Thomas Gard and Monika Hansen and Hanna Jisser and Fredrik Johansen and Berglind Jonsdottir and Silvija Jovic and Larsson, {Helena Elding} and Marielle Lindstr{\"o}m and Markus Lundgren and Marlena Maziarz and Maria M{\aa}nsson-Martinez and Maria Markan and Jessica Melin and Zeliha Mestan and Caroline Nilsson and Karin Ottosson and Kobra Rahmati and Anita Ramelius and Falastin Salami and Anette Sj{\"o}berg and Birgitta Sj{\"o}berg and Malin Svensson and Carina T{\"o}rn and Anne Wallin and {\AA}sa Wimar and Sofie {\AA}berg and Hagopian, {William A.} and Michael Killian and Crouch, {Claire Cowen} and Jennifer Skidmore and Masumeh Chavoshi and Rachel Hervey and Rachel Lyons and Arlene Meyer and Denise Mulenga and Jared Radtke and Matei Romancik and Davey Schmitt and Sarah Zink and Dorothy Becker and Margaret Franciscus and Smith, {Mary Ellen Dalmagro Elias} and Ashi Daftary and Klein, {Mary Beth} and Chrystal Yates and Krischer, {Jeffrey P.} and Sarah Austin-Gonzalez and Maryouri Avendano and Sandra Baethke and Rasheedah Brown and Brant Burkhardt and Martha Butterworth and Joanna Clasen and David Cuthbertson and Stephen Dankyi and Christopher Eberhard and Steven Fiske and Jennifer Garmeson and Veena Gowda and Kathleen Heyman and Belinda Hsiao and Christina Karges and Laras, {Francisco Perez} and Lee, {Hye Seung} and Qian Li and Shu Liu and Xiang Liu and Kristian Lynch and Colleen Maguire and Jamie Malloy and Cristina McCarthy and Aubrie Merrell and Hemang Parikh and Ryan Quigley and Cassandra Remedios and Chris Shaffer and Laura Smith and Susan Smith and Noah Sulman and Roy Tamura and Dena Tewey and Michael Toth and Ulla Uusitalo and Kendra Vehik and Ponni Vijayakandipan and Keith Wood and Jimin Yang and Michael Abbondondolo and Lori Ballard and David Hadley and Wendy McLeod and Steven Meulemans and Beena Akolkar and Kasia Bourcier and Thomas Briese and Johnson, {Suzanne Bennett} and Eric Triplett and Liping Yu and Dongmei Miao and Polly Bingley and Alistair Williams and Kyla Chandler and Olivia Ball and Ilana Kelland and Sian Grace and Henry Erlich and Mack, {Steven J.} and Fear, {Anna Lisa} and Oliver Fiehn and Bill Wikoff and Brian Defelice and Dmitry Grapov and Tobias Kind and Mine Palazoglu and Luis Valdiviez and Benjamin Wancewicz and Gert Wohlgemuth and Joyce Wong and Rich, {Stephen S.} and Chen, {Wei Min} and Suna Onengut-Gumuscu and Emily Farber and Pickin, {Rebecca Roche} and Jonathan Davis and Jordan Davis and Dan Gallo and Jessica Bonnie and Paul Campolieto",

note = "Publisher Copyright: {\textcopyright} 2020 by the American Diabetes Association.",

year = "2020",

month = mar,

day = "1",

doi = "10.2337/db19-0756",

language = "English (US)",

volume = "69",

pages = "465--476",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "3",

}

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 - Rewers, Marian

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 - Ziegler, Anette G.

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 - Lernmark, Åke

AU - Agardh, Daniel

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AU - Ask, Maria

AU - Bennet, Rasmus

AU - Cilio, Corrado

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AU - Fors, Annika

AU - Fransson, Lina

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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

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AU - Killian, Michael

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AU - Skidmore, Jennifer

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AU - Meyer, Arlene

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AU - Hsiao, Belinda

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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

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 - http://www.scopus.com/inward/record.url?scp=85081143063&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85081143063&partnerID=8YFLogxK

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 -

Longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the TEDDY study

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