This project, called also The Diabetes Autoimmunity Study in the Young (DAISY), began in July 1993 and allowed the investigators to establish two unique cohorts of very young children who are at increased (up to 20-fold) risk of insulin-dependent diabetes mellitus (IDDM): (i) a cohort of nearly 300 siblings and offspring, aged initially 0-7 years, relatives of persons with IDDM, and (ii) a cohort of approximately 500 newborns with IDDM associated HLA-DR, DQ alleles, identified through a cord blood screening of 10,000 general population children without a relative with IDDM. In the next 5 years, the investigators are proposing: 1. to continue the follow-up of the sibling/offspring cohort until the mean age of 10 yrs, and of the general population newborn cohort until the mean age of 6 yrs, to further define the natural history of beta-cell autoimmunity, and to sustain this population laboratory for additional studies of IDDM and other autoimmune diseases; 2. to complete, with sufficient power, already initiated studies of dietary and viral determinants of beta-cell autoimmunity and its persistence; 3. to develop automated reliable high-throughput methods, using dried blood blots, to screen for the following: a) the HLA-DRB1*03/*04, DQB1*0302 genotype that is present in 2% of the general population, but in 35-50% of IDDM children, b) autoantibodies against beta-cell antigens GAD65, ICA512 (IA-2), and phogrin; and 4. using these high-throughput methods: a) to screen an estimated 50,000 Colorado newborns for the high risk HLA-DRB1*03/*04, DQB1*0302 genotype, and b) to enroll 780 of an estimated 1,170 eligible high risk children in a prospective follow-up, similar to that already underway, with assessment of selected environmental exposures and yearly screening for beta-cell autoantibodies. The investigators point out that the study is filling an important gap in the understanding of the events leading to IDDM. They further state that the proposed follow-up of this large high risk population will likely bring more complete understanding of IDDM cases and prevention opportunities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK032493-17
Application #
6176581
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Akolkar, Beena
Project Start
1983-07-01
Project End
2001-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
17
Fiscal Year
2000
Total Cost
$598,849
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Frohnert, Brigitte I; Laimighofer, Michael; Krumsiek, Jan et al. (2018) Prediction of type 1 diabetes using a genetic risk model in the Diabetes Autoimmunity Study in the Young. Pediatr Diabetes 19:277-283
Steck, Andrea K; Dong, Fran; Frohnert, Brigitte I et al. (2018) Predicting progression to diabetes in islet autoantibody positive children. J Autoimmun 90:59-63
Liu, Chih-Wei; Bramer, Lisa; Webb-Robertson, Bobbie-Jo et al. (2018) Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression. J Proteomics 172:100-110
Waugh, Kathleen; Snell-Bergeon, Janet; Michels, Aaron et al. (2017) Increased inflammation is associated with islet autoimmunity and type 1 diabetes in the Diabetes Autoimmunity Study in the Young (DAISY). PLoS One 12:e0174840
Gu, Yong; Zhao, Zhiyuan; High, Hilary et al. (2017) Islet Autoantibody Detection by Electrochemiluminescence (ECL) Assay. J Clin Cell Immunol 8:
Liu, Edwin; Dong, Fran; BarĂ³n, Anna E et al. (2017) High Incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes. Gastroenterology 152:1329-1336.e1
Frohnert, Brigitte I; Ide, Lisa; Dong, Fran et al. (2017) Late-onset islet autoimmunity in childhood: the Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia 60:998-1006
Yu, Liping; Zhao, Zhiyuan; Steck, Andrea K (2017) T1D Autoantibodies: room for improvement? Curr Opin Endocrinol Diabetes Obes 24:285-291
Liu, Chih-Wei; Bramer, Lisa; Webb-Robertson, Bobbie-Jo et al. (2017) Temporal profiles of plasma proteome during childhood development. J Proteomics 152:321-328
Gesualdo, Patricia D; Bautista, Kimberly A; Waugh, Kathleen C et al. (2016) Feasibility of screening for T1D and celiac disease in a pediatric clinic setting. Pediatr Diabetes 17:441-8

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