DESCRIPTION (provided by applicant): Research has documented the emergence of macrovascular and microvascular disease among youth with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Little is known about the role of nutritional factors in the emergence of these complications. The proposed study is a continuation of the SEARCH Nutrition Ancillary Study (SNAS1; funded NIH/NIDDK), and ancillary to the SEARCH for Diabetes in Youth project (SEARCH; CDC/DDT and NIH/NIDDK funded). SEARCH includes incident DM cases diagnosed when <20 years of age, from 2002-present, and has a baseline research visit. The SEARCH Cohort study includes a follow-up research visit for SEARCH participants with DM diagnosed in 2002-2006 and 2008 with DM duration >5 years. The aims of SNAS1 included identification of nutritional factors associated with beta cell function and cardiovascular (CVD) risk factors in youth with T1DM at the baseline visit. SNAS2 is a natural extension of SNAS1 and will examine the associations of nutritional factors with macro- and microvascular complications in youth with T1DM and T2DM using cross-sectional and longitudinal designs. Exposure data from the baseline and Cohort Study visits will include plasma nutrient biomarkers (fatty acids, vitamins D and E), and data from a food frequency questionnaire incorporating measurement error modeling. We will address the following aims separately among youth with T1DM (n=2,710) and T2DM (n=435): Aim 1: To evaluate selected nutritional factors in relation to markers of subclinical CVD (pulse wave velocity, augmentation index, and retinal vessel diameter), hypothesizing that specific saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), the ratio of n-3 to n-6 PUFA, vitamins D and E, fiber, fructose, and dietary patterns (Dietary Approaches to Stop Hypertension, Mediterranean, a statistically derived dietary pattern) will be associated with these markers. Aim 2: To evaluate selected nutritional factors in relation to markers of diabetic retinopathy (DR), hypothesizing tha vitamins D and E, PUFA, and dietary patterns will be inversely associated with DR. Aim 3: To evaluate selected nutritional factors in relation to markers of diabetic kidney disease (DKD; urine
albumin:creatinine ratio [UACR]) and estimated glomerular filtration rate [eGFR]) and its progression (UACR), hypothesizing that specific SFA, PUFA, vitamins D and E, and dietary patterns will be associated with DKD. The SNAS2 study leverages and expands data from one of the largest cohort of youth with DM ever assembled to answer critical research questions regarding nutrition and DM complications. Additionally, this study will employ enhanced and novel analytic methods to examine these highly clinically relevant questions. Results will inform nutrition recommendations for youth with DM and provide the much needed scientific basis for clinical trials employing nutritional approaches to reduce risk of macro- and microvascular complications.