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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.
Diabetes. 2020 Oct 26 [Online ahead of print]D

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.

Authors+Show Affiliations

Health Informatics Institute, University of South Florida, Tampa, FL, USA. Qian.Li@epi.usf.edu.Health Informatics Institute, University of South Florida, Tampa, FL, USA.Health Informatics Institute, University of South Florida, Tampa, FL, USA.Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland.Department of Clinical Sciences, Clinical Research Centre, Skåne University Hospital, Lund University, Malmo, Sweden.Pacific Northwest Research Institute, Seattle, Washington, USA.Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.Department of Pediatrics, Turku University Hospital, Turku, Finland. Department of Physiology, University of Turku, Turku, Finland.Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany. Forschergruppe Diabetes, Technical University of Munich, Klinikum Rechts der Isar, Munich, Germany. Forschergruppe Diabetes e.V. at Helmholtz Zentrum München, Munich, Germany.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.Health Informatics Institute, University of South Florida, Tampa, FL, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33106256

Citation

Li, Qian, et al. "Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study." Diabetes, 2020.
Li Q, Liu X, Yang J, et al. Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study. Diabetes. 2020.
Li, Q., Liu, X., Yang, J., Erlund, I., Lernmark, Å., Hagopian, W., Rewers, M., She, J. X., Toppari, J., Ziegler, A. G., Akolkar, B., & Krischer, J. P. (2020). Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study. Diabetes. https://doi.org/10.2337/db20-0696
Li Q, et al. Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study. Diabetes. 2020 Oct 26; PubMed PMID: 33106256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study. 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, AU - ,, Y1 - 2020/10/26/ PY - 2020/07/01/received PY - 2020/10/19/accepted PY - 2020/10/27/entrez PY - 2020/10/28/pubmed PY - 2020/10/28/medline JF - Diabetes JO - Diabetes 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 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. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/33106256/Plasma_Metabolome_and_Circulating_Vitamins_Stratified_Onset_Age_of_an_Initial_Islet_Autoantibody_and_Progression_to_Type_1_Diabetes:_the_TEDDY_Study L2 - https://diabetes.diabetesjournals.org/lookup/pmidlookup?view=long&pmid=33106256 DB - PRIME DP - Unbound Medicine ER -
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