Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
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Nutrigenetics & -genomics of Vitamin D and Omega-3 Fatty Acids in Type 1 Diabetes

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? DESCRIPTION (provided by applicant): The incidence of type 1 diabetes (T1D), one of the most common chronic diseases of childhood, is increasing, perhaps due to decreases in protective factors. While vitamin D and omega-3 fatty acids have been hypothesized to be protective dietary factors for T1D, the evidence supporting their role is either contradictory or lacking. Many nutrition epidemiology studies rely on self-reported dietary intake information, which can be subjective and inaccurate, making it difficult to understand the role of diet in disease development. There exists a critical need for independent assessment of dietary intake via metabolomics profiling and for reliable predictors that connect nutrient metabolism with the etiology of the disease process. Metabolomic profiling can be used as an independent marker of dietary intake and metabolism within the body. T1D is a complex chronic disease, with multiple genetic and environmental risk factors influencing critical time-points in the disease's natural history; therefore, it is necessary to combine prospectively-collected dietary data with dietary biomarkers, metabolites, genetic variants, DNA methylation and gene expression data in order to more fully understand the pathways involved. For example, it is not known whether omega-3 fatty acids and vitamin D interact with genetic variants (nutrigenetics), or whether they alter gene expression, via epigenomic changes (nutrigenomics), to reduce risk for islet autoimmunity (IA), the pre-clinical phase that precedes T1D, and T1D itself. The Diabetes Autoimmunity Study in the Young (DAISY) cohort of 2,547 children at increased T1D risk has made substantial progress in elucidating the nutritional etiology of IA and T1D, although this has highlighted the complexities of the relationships and limitations of the tools of associational epidemiology. We propose to conduct a nested case-control study using the prospectively collected data in DAISY. The overall aim of the study is to elucidate the nutrition epidemiological findings regarding vitamin D and omega-3 fatty acids and risk of IA and T1D using cutting-edge metabolomics, nutrigenetic and nutrigenomics techniques. We propose to further explore the nutrition epidemiology of T1D by supplementing existing nutrition and biomarker data with vitamin D binding protein (in order to calculate free 25[OH]D), and metabolites related to vitamin D and omega-3 fatty acid pathways, in order to obtain an assessment of intake and nutrient metabolism, independent of self-reported intake. We will then explore the nutrigenetics of T1D by examining whether the effect of vitamin D and omega-3 fatty acids on IA and T1D differs by genetic variation. Finally, we will explore the nutrigenomics of T1D by investigating whether vitamin D and omega-3 fatty acid intake alter gene expression, via epigenetic changes, to influence predisposition to T1D. There are significant gaps in understanding the biologic mechanisms underlying the association between vitamin D and omega-3 fatty acids and the development of IA and T1D. Elucidating these mechanisms is critical for the development of prevention and treatment strategies aimed at reducing the burden of T1D.
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