Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study

Objective: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and non-diabetic controls persist, worsen or improve as children grow into puberty, and whether differences are associated with hyperglycemia.

Research Design & Methods: 144 children with type 1 diabetes and 72 non-diabetic age-matched controls, mean±SD age 7.0±1.7 years at baseline, 46% female, had unsedated magnetic resonance imaging and cognitive testing up to 4 times over 6.4±0.4 years (5.3-7.8); HbA1_C and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed effects models at 6, 8, 10 and 12 years. Correlations with glycemia were performed.

Results: Total brain, gray and white matter volumes, full-scale and verbal IQ were lower in the diabetes group [at 6, 8, 10 and 12 years estimate group differences in full-scale IQ respectively:

-4.15, -3.81, -3.46, -3.11, p <0.05; total brain volume: -15410 mm³x10³, -21159, -25548,

-28577, p <0.05 at 8, 10 and 12 years]. Differences at baseline persisted or increased over time, brain volumes and cognitive scores negatively correlated with a life-long HbA1_C index and higher sensor glucose in diabetes.

Conclusions: Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children.