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

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 En...

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Autores principales: Li, Qian, Parikh, Hemang, Butterworth, Martha D., Lernmark, Åke, Hagopian, William, Rewers, Marian, She, Jin-Xiong, Toppari, Jorma, Ziegler, Anette-G., Akolkar, Beena, Fiehn, Oliver, Fan, Sili, Krischer, Jeffrey P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034190/
https://www.ncbi.nlm.nih.gov/pubmed/32029481
http://dx.doi.org/10.2337/db19-0756
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author Li, Qian
Parikh, Hemang
Butterworth, Martha D.
Lernmark, Åke
Hagopian, William
Rewers, Marian
She, Jin-Xiong
Toppari, Jorma
Ziegler, Anette-G.
Akolkar, Beena
Fiehn, Oliver
Fan, Sili
Krischer, Jeffrey P.
author_facet Li, Qian
Parikh, Hemang
Butterworth, Martha D.
Lernmark, Åke
Hagopian, William
Rewers, Marian
She, Jin-Xiong
Toppari, Jorma
Ziegler, Anette-G.
Akolkar, Beena
Fiehn, Oliver
Fan, Sili
Krischer, Jeffrey P.
author_sort Li, Qian
collection PubMed
description 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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spelling pubmed-70341902021-03-01 Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study Li, Qian Parikh, Hemang Butterworth, Martha D. Lernmark, Åke Hagopian, William Rewers, Marian She, Jin-Xiong Toppari, Jorma Ziegler, Anette-G. Akolkar, Beena Fiehn, Oliver Fan, Sili Krischer, Jeffrey P. Diabetes Genetics/Genomes/Proteomics/Metabolomics 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. American Diabetes Association 2020-03 2020-02-13 /pmc/articles/PMC7034190/ /pubmed/32029481 http://dx.doi.org/10.2337/db19-0756 Text en © 2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Li, Qian
Parikh, Hemang
Butterworth, Martha D.
Lernmark, Åke
Hagopian, William
Rewers, Marian
She, Jin-Xiong
Toppari, Jorma
Ziegler, Anette-G.
Akolkar, Beena
Fiehn, Oliver
Fan, Sili
Krischer, Jeffrey P.
Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
title Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
title_full Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
title_fullStr Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
title_full_unstemmed Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
title_short Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
title_sort longitudinal metabolome-wide signals prior to the appearance of a first islet autoantibody in children participating in the teddy study
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034190/
https://www.ncbi.nlm.nih.gov/pubmed/32029481
http://dx.doi.org/10.2337/db19-0756
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