Type 1 diabetes (T1D) affects 1.4 million people in the U.S. and its incidence has doubled over the past 20 years. The Diabetes Autoimmunity in the Young Study (DAISY) has already provided new clues concerning the etiology and natural history of T1D in early childhood. We hypothesize that the development of T1D reflects two processes, activation of autoimmunity and then relapsing-remitting islet destruction. With the increasing age of the cohort, we are proposing in this application to address unanswered research challenges: 1) To continue the follow-up of the existing cohort until the age of 18 yrs to determine the natural history of islet autoimmunity (IA) and other autoimmune phenotypes and to explore the heterogeneity of IA and T1D in children and adolescents. We will follow for 5 more years already established cohorts of general population children with high risk HLA-DR,DQ genotypes (n=1422) and non-diabetic first degree relatives of patients with T1D (n=1,120), current median age 12.8 yr. We will estimate overall burden of pre-clinical and clinical T1D, celiac, thyroid, adrenal, rheumatic and parietal autoimmune disease in the general population of Colorado by age 18. This will inform future screening and prevention programs. We will further explore the apparent heterogeneity of IA and T1D and its implications for adult-onset diabetes. 2) To evaluate selected environmental risk factors as potential initiators of IA and/or promoters of progression to T1D. The proposed additional follow-up will extend the scope of this study to T1D cases expected between ages 12-18 yr - the peak incidence of T1D. We will continue to evaluate candidate risk factors that appear to operate only as triggers of IA, but also focus on factors that become more important with age and may be the key promoters of progression from IA to T1D. Alternatively, we will seek the factors that slow down the progression and may help IA to remit. 3) To define the effects of early diagnosis and treatment on preservation of endogenous insulin, glycemic control and variability, and quality of life in children with screening-identified T1D. Screening-detected patients avoid ketoacidosis at diagnosis and have higher fasting C-peptide levels, lower HbA1c, and lower insulin dose during the initial year post-diagnosis than community controls. However, no longer-term follow-up data exist to rule out a lead-time bias and confirm the benefit of screening. The proposed studies are important to reach our overarching goals: to find the environmental causes of T1D, develop primary prevention, and inform public health screening for several autoimmune disorders in children and adolescents. We will continue to make every effort to share DAISY resources with multiple investigators studying T1D and other autoimmune diseases, striving for an open-source database and repository.

Public Health Relevance

Type 1 diabetes (T1D) affects 1.4 million people in the U.S. and its incidence has doubled over the past 20 years. The Diabetes Autoimmunity in the Young Study (DAISY) will estimate overall burden of T1D and other autoimmune diseases in the general population by age 18. It will evaluate environmental risk factors for T1D and define the effects of early diagnosis and treatment. The study will share resources with multiple investigators studying autoimmune diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK032493-31
Application #
8667421
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Spain, Lisa M
Project Start
1994-11-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
31
Fiscal Year
2014
Total Cost
$639,249
Indirect Cost
$217,814
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
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
Frohnert, Brigitte I; Laimighofer, Michael; Krumsiek, Jan et al. (2017) Prediction of type 1 diabetes using a genetic risk model in the Diabetes Autoimmunity Study in the Young. Pediatr Diabetes :
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
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
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
Simmons, Kimber M; McFann, Kim; Taki, Iman et al. (2016) Reduced Bone Mineral Density Is Associated with Celiac Disease Autoimmunity in Children with Type 1 Diabetes. J Pediatr 169:44-8.e1
Steck, Andrea K; Dong, Fran; Waugh, Kathleen et al. (2016) Predictors of slow progression to diabetes in children with multiple islet autoantibodies. J Autoimmun 72:113-7
Zhao, Zhiyuan; Miao, Dongmei; Waugh, Kathleen et al. (2016) Higher Sensitivity and Earlier Identification of Celiac Disease Autoimmunity by a Nonradioactive Assay for Transglutaminase Autoantibodies. J Immunol Res 2016:2904563
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
Zhao, Zhiyuan; Miao, Dongmei; Michels, Aaron et al. (2016) A multiplex assay combining insulin, GAD, IA-2 and transglutaminase autoantibodies to facilitate screening for pre-type 1 diabetes and celiac disease. J Immunol Methods 430:28-32

Showing the most recent 10 out of 190 publications