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

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

Abstrakti

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.

AlkuperäiskieliEnglanti
Sivut282–292
JulkaisuDiabetes
Vuosikerta70
Numero1
Varhainen verkossa julkaisun päivämäärä26 lokak. 2020
DOI - pysyväislinkit
TilaJulkaistu - 2021
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

  • Jufo-taso 3

Sormenjälki

Sukella tutkimusaiheisiin 'Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study'. Ne muodostavat yhdessä ainutlaatuisen sormenjäljen.

Siteeraa tätä