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

UNLABELLED: Type 1 diabetes has detrimental effects in white matter microstructure. In a longitudinal study, we investigated whether these reported findings change as children grow and enter puberty. At study entry, there were 143 children with type 1 diabetes and 71 control participants without diabetes, 4-9 years old. Brain MRI using diffusion tensor imaging, neurocognitive, and glycemic assessments were performed four times 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 control participants) who had testing at time 4 that FA increased, and RD, AD, and 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 control participants at 6-10 years. Differences were not detected at 12 years (age imputed from data), when in puberty. Higher blood glucose levels are associated with lower FA and higher RD and MD. Higher glucose percentage 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 AD was decreased in children with diabetes, less so during puberty, and FA was reciprocally related to hyperglycemia. These data suggest continued negative impact of chronic hyperglycemia in the developing brain.

ARTICLE HIGHLIGHTS: Type 1 diabetes has detrimental effects in white matter in young children. We performed a longitudinal study using brain MRI (diffusion tensor imaging) and cognitive assessments in 4- to 9-year-old children, control participants without diabetes (n = 71) and with type 1 diabetes (n = 143), plus continuous glucose monitoring, to assess changes at four time points as children grow over 6-8 years. White matter myelination and fiber integrity were assessed using axial diffusivity, which was decreased in the diabetes versus control group, less so during puberty, and fractional anisotropy was reciprocally related to hyperglycemia. Data suggest continued negative impact of chronic hyperglycemia in the developing brain.