Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study

Research output: Contribution to journalArticle

Abstract

Children's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.

Details

Authors
Organisations
External organisations
  • Farr Institute of Health Informatics Research
  • University of South Florida; Department of Sociology
  • Shriners Hospitals for Children, Tampa
  • University of South Florida
  • Finnish National Institute for Health and Welfare
  • Pacific Northwest Diabetes Research Institute
  • University of Colorado-Denver
  • Augusta University
  • Turku University Hospital
  • Jalisco Institute of Diabetes and Obesity Research SC
  • National Institutes Of Health Clinical Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)282-292
Number of pages11
JournalDiabetes
Volume70
Issue number1
Early online date2020 Oct 26
Publication statusPublished - 2021 Jan
Publication categoryResearch
Peer-reviewedYes