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Li, Q.* ; Liu, X.* ; Yang, J.* ; Erlund, I.* ; Lernmark, A.* ; Hagopian, W.* ; Rewers, M.* ; She, J.X.* ; Toppari, J.* ; Ziegler, A.-G. ; Akolkar, B.* ; Krischer, J.P.*

Plasma metabolome and circulating vitamins stratified onset age of an initial islet autoantibody and progression to type 1 diabetes: The TEDDY Study.

Diabetes 70, 282-292 (2021)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Beta-cell Autoimmunity; Environmental Determinants; Ascorbic-acid; Amino-acid; Risk; Children; Childhood; Association; Discovery; Lipidome
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 70, Issue: 1, Pages: 282-292 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Grants National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards
JDRF
National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, Centers for Disease Control and Prevention
National Institute of Diabetes and Digestive and Kidney Diseases