Cognitive, structural and functional impact of new onset type 1 diabetes on the brain of young children: Understanding risks and protective factors - An increasing body of data show the brain is a target of diabetes complications. We and others have investigated
the impact of type 1 diabetes (T1D) in the developing brain in children as young as 4-years old. Using structural
and functional brain MRI, neurocognitive assessments, and continuous glucose monitoring (CGM) we observed
quantifiable differences in gray and white matter volume (and microstructure) in children with T1D compared to
age-matched nondiabetic controls, and meaningful differences in working memory, executive function scores,
and performance IQ. These differences widened when children were followed at 4-time points over nearly 8-
years, findings strongly correlated to hyperglycemia. This Funding Opportunity seeks to further investigate
neurocognitive and psychosocial function now in children with new onset diabetes, including those of diverse
racial and socioeconomic (SES) backgrounds. This is timely given our preliminary data raise important questions
as to the impact of better normalization of blood glucose using advanced insulin delivery (AID)/closed-loop
systems. We propose an observational, longitudinal study in a large cohort of 4-10-year old prepubertal children
with new onset T1D (n=525) presenting with or without diabetic ketoacidosis (DKA), studied within 4-6 weeks of
diagnosis, compared to age-matched nondiabetic controls (preferably siblings and classmates) (n=175).
Primary Aims: (1) To determine their neurocognitive function (principal); (2) To correlate neurocognitive
function scores with metrics of dysglycemia, and severity of diabetes and DKA at presentation; (3) To assess
patient/family reported perceptions of quality of life, including diabetes distress and psychosocial aspects, in
children, and mood in parents; (4) To correlate above AIMS with use of AID closed-loop technologies; (5) To
assess structural gray and white matter volume and white matter microstructure and functional (f)MRI during
cognitive tasks (baseline & 24-months). Pertinent social determinants of health (SDOH) will be collected, and all
outcomes adjusted by sex and SES and level of glycemia. To accomplish this, we will perform standardized
neurocognitive testing using NIH toolbox, psychosocial assessments, structural and functional MRI using
multimodal imaging, CGM downloads and HbA1c, SDOH data collected using NIH toolbox PhenX. Children will
be recruited across 10 centers selected along a Biostatistical Research Core, in a new network. Children with
T1D will be followed quarterly, CGM and pump (if applicable) data downloaded, principal assessments done at
baseline, 12 and 24-months. This principal investigator, and the experienced team assembled, would bring
considerable expertise and strength to the new network, with an outstanding record of accomplishments studying
T1D and the brain in children and well-established clinical and research infrastructure. This innovative proposal
is a prototype of the observational study we can perform. Results will offer critical insight on developmental and
cognitive trajectories in young children with new onset T1D, racially and socioeconomically diverse, and whether
better glycemic control, including early use of AID technology can prevent or improve cognitive outcomes.
