TY - JOUR
T1 - Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes
T2 - The TEDDY Study
AU - TEDDY study group
AU - Li, Qian
AU - Liu, Xiang
AU - Yang, Jimin
AU - Erlund, Iris
AU - Lernmark, Åke
AU - Hagopian, William
AU - Rewers, Marian
AU - She, Jin Xiong
AU - Toppari, Jorma
AU - Ziegler, Anette G.
AU - Akolkar, Beena
AU - Krischer, Jeffrey P.
N1 - Publisher Copyright:
© 2020 by the American Diabetes Association.
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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 Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 newborns by screening of 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], and erythrocyte membrane fatty acids following birth until IA seroconversion under a nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or GAD (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 with nonprogressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, and alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA case subjects but not in matched control subjects, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.
AB - 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 Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 newborns by screening of 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], and erythrocyte membrane fatty acids following birth until IA seroconversion under a nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or GAD (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 with nonprogressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, and alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA case subjects but not in matched control subjects, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.
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U2 - 10.2337/db20-0696
DO - 10.2337/db20-0696
M3 - Article
C2 - 33106256
AN - SCOPUS:85099072947
VL - 70
SP - 282
EP - 292
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 1
ER -