UNITED: Understanding neurocognitive outcomes in Type 1 diabetes: Modifiable risk and protective factors in diverse youth

PROJECT SUMMARY Growing evidence suggests that individuals with Type 1 diabetes mellitus (T1D) are at risk for cognitive dysfunction over time, with approximately 28% of middle-aged adults with T1D and 48% of older adults with T1D meeting criteria for clinically significant cognitive impairment. Our team and others have shown early appearing differences in brain structure and selected cognitive functions, with differing trajectories over time in children with T1D. However, significant variability in outcomes remains unexplained, and there is debate about the mechanisms and modifiable factors contributing to these neurocognitive deficits. Studying early cognitive, functional, and structural effects in young patients with T1D before complications occur is a necessary step towards informing risk factors, critical periods for prevention and intervention, and strategies to mitigate the risk of neurocognitive complications of T1D later in life. Previous work has not been adequately powered or designed to determine the effects of potential modifiable or protective risk factors for brain outcomes, how T1D factors influence dynamic cognitive function in real-world settings and whether individuals with T1D from diverse socioeconomic situations face greater risk for altered brain outcomes. We propose to address these deficiencies by first engaging community stakeholders from diverse backgrounds to better understand families' perspectives and needs. Their input will then guide the specific recruitment and data collection methodology that we employ for this longitudinal study of diverse, prepubertal children with newly diagnosed T1D and their siblings without T1D. In sum, this work will provide a definitive view of the complex risk and protective factors shaping neurodevelopment in a diverse group of children with T1D and will help identify critical targets for intervention to promote optimal brain and cognitive outcomes.