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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • University of South Florida
  • Pacific Northwest Diabetes Research Institute
  • University of Colorado-Denver
  • Augusta University
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • University of California, Davis
  • Skåne University Hospital
  • University of Turku
  • Turku University Hospital
  • Helmholtz Zentrum München
  • Technical University of Munich
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Pediatrics
Original languageEnglish
Pages (from-to)465-476
Number of pages12
JournalDiabetes
Volume69
Issue number3
Early online date2020 Feb 6
Publication statusPublished - 2020 Mar 1
Publication categoryResearch
Peer-reviewedYes