Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study

• Published in: Diabetes/metabolism research and reviews Vol. 30; no. 5; pp. 424 - 434
• Main Authors: Lee, Hye-Seung, Burkhardt, Brant R., McLeod, Wendy, Smith, Susan, Eberhard, Chris, Lynch, Kristian, Hadley, David, Rewers, Marian, Simell, Olli, She, Jin-Xiong, Hagopian, Bill, Lernmark, Ake, Akolkar, Beena, Ziegler, Anette G., Krischer, Jeffrey P.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-07-2014; Wiley Subscription Services, Inc
• Subjects: Autoantibodies - analysis; Autoantibodies - immunology; batch effects; biomarker discovery; Biomarkers - analysis; Case-Control Studies; Clinical Medicine; Diabetes Mellitus, Type 1 - immunology; Diet; Endocrinology and Diabetes; Endokrinologi och diabetes; Epidemiologic Methods; Gene Expression; Humans; Islets of Langerhans - immunology; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolomics; Metagenomics; Microbiota; nested case-control design; TEDDY; type 1 diabetes; TEDDY; nested case-control design; type 1 diabetes; biomarker discovery; batch effects
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.2510

Aims
The Environmental Determinants of Diabetes in the Young planned biomarker discovery studies on longitudinal samples for persistent confirmed islet cell autoantibodies and type 1 diabetes using dietary biomarkers, metabolomics, microbiome/viral metagenomics and gene expression.
Methods
This article describes the details of planning The Environmental Determinants of Diabetes in the Young biomarker discovery studies using a nested case–control design that was chosen as an alternative to the full cohort analysis. In the frame of a nested case–control design, it guides the choice of matching factors, selection of controls, preparation of external quality control samples and reduction of batch effects along with proper sample allocation.
Results and conclusion
Our design is to reduce potential bias and retain study power while reducing the costs by limiting the numbers of samples requiring laboratory analyses. It also covers two primary end points (the occurrence of diabetes‐related autoantibodies and the diagnosis of type 1 diabetes). The resulting list of case–control matched samples for each laboratory was augmented with external quality control samples. Copyright © 2013 John Wiley & Sons, Ltd.