Mapping Neurocognitive Complications of Pediatric Type 1 Diabetes (T1D) and Potential Risk and Protective Factors - Modified Project Summary/Abstract Section Type 1 diabetes (T1D) is associated with neurocognitive complications that may emerge early after diagnosis and worsen over time. Risk may be pronounced in children diagnosed prepubertally, as the developing brain is likely particularly vulnerable to dysglycemia, diabetic ketoacidosis (DKA), and other metabolic disturbances associated with T1D. Although prior studies suggest that early age of onset, glycemic variability, hyperglycemia, hypoglycemia, and DKA may adversely affect cognitive development, the mechanisms underlying these associations remain poorly understood. Existing studies have generally been limited by small sample sizes, cross-sectional designs, and/or incomplete characterization of clinical, neurocognitive, neuroimaging, and environmental factors that may influence outcomes. Understanding underlying mechanisms is vital. The Brain Research Alliance in Youth with Type 1 Diabetes (BRAINY-T1D) Study is a prospective, multicenter longitudinal cohort study designed to identify risk and protective factors for neurocognitive outcomes in prepubertal children with recently diagnosed T1D. In partnership with a centralized Biostatistics Research Center, other clinical centers, and specialized laboratory, phenotyping, and neuroimaging cores, our UNC site will implement a harmonized protocol and enroll children with T1D and demographically similar children without diabetes. The study will enroll prepubertal children ages 4 to 9 years. Children with T1D will be enrolled within 3–6 months of diagnosis and followed for approximately 18 months. The primary objective is to determine whether greater time in target glucose range is associated with protection against neurocognitive difficulties. Additional objectives include evaluating whether DKA at diagnosis, age at diabetes onset, glycemic variability, and other diabetes-related factors predict neurocognitive outcomes and brain development. Participants undergo comprehensive longitudinal assessments including neuropsychological testing, multimodal brain MRI, continuous glucose monitoring metrics, laboratory evaluations, physical activity and sleep monitoring, and detailed measures of psychosocial functioning, family environment, diet, and diabetes management. Repeated assessments will allow investigators to characterize trajectories of neurocognitive development over time, while identifying factors that may increase vulnerability or confer resilience. Through close collaboration with participating families and community stakeholders, we aim to generate critical knowledge regarding the neurodevelopmental consequences of pediatric T1D and identify modifiable factors that can be targeted to improve long-term cognitive and health outcomes. Findings from BRAINY-T1D are expected to inform future interventions, diabetes technologies, and clinical care strategies designed to reduce neurocognitive complications and improve quality of life for children living with T1D.
