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

Qian Li, Xiang Liu, Jimin Yang, Iris Erlund, Åke Lernmark, William Hagopian, Marian Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, TEDDY Study Group, Suvi Ahonen, Mari Åkerlund, Leena Hakola, Heikki Hyöty, Mirva Koreasalo, Kalle Kurppa, Maria LönnrotMarkus Mattila, Sami Oikarinen, Anne Riikonen, Suvi Virtanen

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)282–292
JournalDiabetes
Volume70
Issue number1
Early online date26 Oct 2020
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 3

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