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Plasma metabolome and circulating vitamins stratified onset age of an initial islet autoantibody and progression to type 1 diabetes: the TEDDY study
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posted on 2020-10-26, 19:41 authored by Ada AdminAda Admin, 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 GroupChildren’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.