RT Journal Article
SR Electronic
T1 Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP db200696
DO 10.2337/db20-0696
A1 Li, Qian
A1 Liu, Xiang
A1 Yang, Jimin
A1 Erlund, Iris
A1 Lernmark, Åke
A1 Hagopian, William
A1 Rewers, Marian
A1 She, Jin-Xiong
A1 Toppari, Jorma
A1 Ziegler, Anette-G.
A1 Akolkar, Beena
A1 Krischer, Jeffrey P.
A1 ,
YR 2020
UL http://diabetes.diabetesjournals.org/content/early/2020/10/26/db20-0696.abstract
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 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.