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 control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia. RESEARCH DESIGN AND METHODS One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean +/- SD age at baseline 7.0 +/- 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 +/- 0.4 (range 5.3-7.8) years; HbA(1c) 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 and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of -4.15, -3.81, -3.46, and -3.11, respectively (P < 0.05), and total brain volume differences of -15,410, -21,159, -25,548, and -28,577 mm(3) at 6, 8, 10, and 12 years, respectively (P < 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA(1c) 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.

Automated summary

The study revealed that children with early-onset type 1 diabetes have persistent differences in brain volumes and cognitive scores compared to control subjects, which are associated with metrics of hyperglycemia and worsen over time. These findings suggest that diabetes has long-term effects on the brains of children and further research is needed to investigate whether these changes can be reversed.