Differences in White Matter Microstructure in Children With Type 1 Diabetes Persist During Longitudinal Follow up: Relation to Dysglycemia

Type 1 diabetes has detrimental effects in white matter microstructure. In a longitudinal study, we investigated if these reported findings change as children grow and enter puberty.

143 children with type 1 diabetes and 71 non-diabetic controls, 4-9 years old at study entry had brain MRI using diffusion tensor imaging, neurocognitive and glycemic assessments at 4 time points across 6-8 years of follow-up. Longitudinal mixed-effects modeling was used to examine changes in fractional anisotropy (FA), axial diffusivity (AD) (measures of myelination and fiber integrity), radial diffusivity (RD) (axonal leakage) and mean diffusivity (MD) (average diffusion). Associations with glycemic and cognitive measures were assessed.

We observed in 182 children (121 type 1 diabetes, vs. 61 controls) who had testing at Time 4 that FA increased, and RD, AD, MD decreased significantly in both groups, with no differences between groups for FA, RD and MD over time. However, children with diabetes had lower AD than controls at 6-10 years, differences not detected at 12 years (age imputed from data), when in puberty. Higher blood sugars are associated with lower FA, higher RD and MD. Higher glucose %Time-in-Range was associated with higher FA, reflecting better fiber integrity and myelination, and higher cognitive metrics. Within the diabetes group AD and MD showed no association with neurocognitive outcomes.

In summary, white matter axial diffusivity was decreased in children with diabetes, less so during puberty, and fractional anisotropy was reciprocally related to hyperglycemia. These data suggest continued negative impact of chronic hyperglycemia in the developing brain.