PROJECT SUMMARY Children with type 1 diabetes (T1D) have small but significant deficits in neurocognitive functioning compared to their peers without diabetes, especially in the areas of memory, learning, and executive function skills. Further, neuroimaging studies consistently observe differences in brain structures and brain development in children with T1D, particularly brain white matter microstructure. These deficits in cognitive function negatively affect children’s ability to manage diabetes effectively, increasing risk for poor glycemic outcomes and further brain insults. Evidence suggests that factors such as diabetic ketoacidosis (DKA) at time of T1D onset and exposure to chronic hyperglycemia or severe hypoglycemia may increase risk or severity of these deficits, but findings are mixed, and many studies were limited by the inclusion of older adolescents or adults with T1D, small, homogenous samples, or cross-sectional designs. Thus, a large prospective study of a diverse sample of school-aged children newly diagnosed with T1D and a matched group of children without diabetes is needed to identify modifiable risk and protective factors for neurocognitive complications in this population. We will over-enroll children from minoritized racial and ethnic groups to understand factors that may contribute to disparities in outcomes. As a Clinical Center, we will work with the Biostatistics Research Core, the NIDDK Project Scientist, and the other centers to finalize the study protocol, including collection of neuroimaging, neurocognitive, and glucose data, and development of neuroimaging harmonization plans. Our multidisciplinary team includes a pediatric psychologist, a pediatric neurologist, a pediatric endocrinologist, and a pediatric neuroradiologist, as well as experts in imaging science and harmonization of imaging data. The Children’s Diabetes Program at Vanderbilt University Medical Center serves a large, diverse population of children with T1D and has a strong history of multicenter collaborations with other pediatric diabetes centers. Further, as recipients of a related U34 award, we engaged with community members, including caregivers of children with T1D, to inform the study aims and protocol. The proposed project will assess hypothesized risk factors (DKA at presentation, glycemic variability, adverse childhood experience, socioeconomic status), as well as potentially modifiable protective factors (child sleep quality, caregiver distress, and use of diabetes devices). In addition, we will optimize neuroimaging protocols and processing tools to allow for harmonization of high-resolution neuroimaging data across sites and scanners for the most robust analysis. Reductions of neuronal density and white matter integrity may be measured non-invasively via advanced MRI of the brain methods. This project has the potential to influence standards of clinical care for children with T1D and to pinpoint critical periods for prevention and inter...