Longitudinal Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: The TEDDY Study

• Activity Number: 46 - Statistical Challenges and Breakthroughs in Diabetes and Obesity Research in the Big Data Era
• Type: Topic-Contributed
• Date/Time: Sunday, August 8, 2021 : 3:30 PM to 5:20 PM
• Sponsor: Section on Bayesian Statistical Science
• Author(s): Qian Li* and Xiang Liu and Jimin Yang and Iris Erlund and Åke Lernmark and William Hagopian and Marian Rewers and Jin-Xiong She and Jorma Toppari and Anette-G Ziegler and Beena Akolkar and Jeffrey Krischer
• Companies: St. Jude Children’s Research Hospital and University of South Florida and University of South Florida and Finnish Institute for Health and Welfare and Lund University and Pacific Northwest Research Institute and University of Colorado Denver and Augusta University and University of Turku and Technical University of Munich and NIDDK/NIH and University of South Florida

Abstract

The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 newborns by screening of HLA-DR-DQ haplogenotypes at six clinical centers in four countries, and collected longitudinal plasma samples following birth for mass spectrometry metabolomics analysis and ascorbic acid, 25-hydroxyvitamin D (25(OH)D) measurement under a nested case-control design. We clustered temporal plasma lipidomes of n=165 cases by applying the Gaussian mixture model and identified a subgroup of children developing autoimmunity at an earlier age compared to the others, similar to the age of population-wide early incidence. Differential analysis showed that children having early onset of autoimmunity had reduced plasma ascorbic acid, cholesterol and sphingomyelins at infant age, while plasma 25(OH)D, diglycerides, lysophosphatidylcholines, triglycerides, and alanine prior to the onset of autoimmunity was associated with progression to T1D. Plasma ascorbic acid and 25(OH)D at infancy were found associated with HLA-DR3/DR4 haplogenotype among cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals.