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
Lamb, Molly M; Miller, Melissa; Seifert, Jennifer A et al. (2015) The effect of childhood cow's milk intake and HLA-DR genotype on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young. Pediatr Diabetes 16:31-8
Steck, Andrea K; Dong, Fran; Taki, Iman et al. (2014) Early hyperglycemia detected by continuous glucose monitoring in children at risk for type 1 diabetes. Diabetes Care 37:2031-3
Jin, Yulan; Sharma, Ashok; Bai, Shan et al. (2014) Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function. Diabetes 63:2506-15
Norris, Jill M; Kroehl, Miranda; Fingerlin, Tasha E et al. (2014) Erythrocyte membrane docosapentaenoic acid levels are associated with islet autoimmunity: the Diabetes Autoimmunity Study in the Young. Diabetologia 57:295-304
Frederiksen, Brittni N; Kroehl, Miranda; Fingerlin, Tasha E et al. (2013) Association between vitamin D metabolism gene polymorphisms and risk of islet autoimmunity and progression to type 1 diabetes: the diabetes autoimmunity study in the young (DAISY). J Clin Endocrinol Metab 98:E1845-51
Ziegler, Anette G; Rewers, Marian; Simell, Olli et al. (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473-9
Narwaney, Komal J; Glanz, Jason M; Norris, Jill M et al. (2013) Association of HLA class II genes with clinical hyporesponsiveness to trivalent inactivated influenza vaccine in children. Vaccine 31:1123-8
Frederiksen, B; Liu, E; Romanos, J et al. (2013) Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY). J Steroid Biochem Mol Biol 133:51-7
Frederiksen, Brittni; Kroehl, Miranda; Lamb, Molly M et al. (2013) Infant exposures and development of type 1 diabetes mellitus: The Diabetes Autoimmunity Study in the Young (DAISY). JAMA Pediatr 167:808-15
Lamb, Molly M; Simpson, Melissa D; Seifert, Jennifer et al. (2013) The association between IgG4 antibodies to dietary factors, islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young. PLoS One 8:e57936

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