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

Li, Qian ; Parikh, Hemang LU ; Butterworth, Martha D ; Lernmark, Åke LU ; Hagopian, William ; Rewers, Marian ; She, Jin-Xiong ; Toppari, Jorma ; Ziegler, Anette-G and Akolkar, Beena , et al. (2020) In Diabetes 69(3). p.465-476
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),... (More)

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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published
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Diabetes
volume
69
issue
3
pages
12 pages
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:32029481
  • scopus:85081143063
ISSN
1939-327X
DOI
10.2337/db19-0756
language
English
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yes
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c11117ac-bc58-43b3-90cf-92395899dfbc
date added to LUP
2020-02-14 18:14:06
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2020-03-24 08:18:48
@article{c11117ac-bc58-43b3-90cf-92395899dfbc,
  abstract     = {<p>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.</p>},
  author       = {Li, Qian and Parikh, Hemang and Butterworth, Martha D and Lernmark, Åke and Hagopian, William and Rewers, Marian and She, Jin-Xiong and Toppari, Jorma and Ziegler, Anette-G and Akolkar, Beena and Fiehn, Oliver and Fan, Sili and Krischer, Jeffrey P},
  issn         = {1939-327X},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {465--476},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study},
  url          = {http://dx.doi.org/10.2337/db19-0756},
  doi          = {10.2337/db19-0756},
  volume       = {69},
  year         = {2020},
}