Identifying Modifiable Risk and Protective Factors for Neurocognitive Complications of Pediatric Type 1 Diabetes

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PROJECT SUMMARY Meta-analytic studies have identified small but significant deficits in neurocognitive functioning in children with type 1 diabetes (T1D) 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. Evidence suggests that factors such as age of onset, diabetic ketoacidosis (DKA) at time of 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 samples or cross-sectional designs. Thus, a large prospective study of young children with T1D followed over time with rigorous assessment and follow-up is needed to identify modifiable risk and protective factors for neurocognitive complications in this population. This U34 planning award will provide the time and resources needed to prepare for an observational, longitudinal cohort study of young children with T1D (age 6 to 10 years at enrollment), and a comparison group of children without diabetes. We will establish contracts with other clinical research centers, obtain data needed to develop neuroimaging harmonization plans, and finalize the protocols, including neuroimaging and neurocognitive testing. Our multidisciplinary team includes a pediatric psychologist, a pediatric neurologist, a pediatric endocrinologist, and a pediatric neuroradiologist; experts in imaging science and harmonization of imaging data, as well as a biostatistician experienced in analyses with imaging data, and a researcher using a novel mobile phone-based method to capture child function in real- time, called ecological momentary assessment. The Children's Diabetes Program (CDP) 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. The proposed project will assess hypothesized risk factors (age of onset, DKA at presentation and glycemic control), as well as potentially modifiable protective factors (child sleep quality, caregiver distress, and use of diabetes devices). In addition, we will optimize imaging protocols and processing tools to allow for harmonization of neuroimaging data across sites and scanners for the most robust analysis. This project has the potential to influence standards of clinical care for children with T1D and to pinpoint critical periods for prevention and intervention to improve brain health and function.