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Persistence of abnormalities in white matter in children with type 1 diabetes
Larry A Fox1, Tamara Hershey2, Nelly Mauras3
1Pediatric Endocrinology, Nemours Children's Health System, 807 Children's Way, Jacksonville, FL, 32207, USA. lfox@nemours.org.
Insights
Children with type 1 diabetes show persistent white matter microstructure alterations. Lower hyperglycemia exposure in these children is linked to better white matter development and cognitive function.
Area of Science:
- Neuroscience
- Pediatrics
- Endocrinology
Background:
- Type 1 diabetes (T1D) in children is associated with altered brain white matter development.
- Hyperglycemia is a suspected contributor to these neurological changes.
Purpose of the Study:
- To investigate the longitudinal impact of dysglycemia on white matter microstructure development in young children with T1D.
- To determine if hyperglycemia exposure influences white matter development trajectories over time.
Main Methods:
- Longitudinal observational study of 118 children with T1D and 58 controls (aged 4-10 years).
- Diffusion tensor imaging (DTI) used to analyze white matter microstructure at baseline and 18 months.
- Continuous glucose monitoring and HbA1c levels collected to assess glycemic control.
Main Results:
- Children with T1D exhibited lower axial diffusivity at both baseline and 18 months, indicating persistent microstructural differences.
- Reduced hyperglycemia exposure since diagnosis correlated with higher fractional anisotropy (FA) in children with T1D.
- Higher FA was positively associated with cognitive performance and full-scale IQ scores.
Conclusions:
- Hyperglycemia in early childhood T1D is linked to altered white matter development trajectories.
- These microstructural changes may underlie cognitive deficits observed in children with T1D.
Aims/Hypothesis:
Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes.
Methods:
One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA1c levels were obtained every 3 months.
Results:
Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02).
Conclusions/Interpretation:
These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.
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