Persistence of abnormalities in white matter in children with type 1 diabetes

Abstract

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 HbA_1c 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.

Keywords: Brain development; Paediatric diabetes; White matter.

Fig. 1

Estimated trajectories of axial (a), radial (b) and mean (c) diffusivity and fractional anisotropy (d) from baseline to 18 months. Dashed black lines, diabetes group; solid black lines, group without diabetes; grey dotted lines, 95% CIs for diabetes group; grey solid lines, 95% CIs for the group without diabetes. *p<0.05, with vs without diabetes at baseline and 18 months in axial diffusivity only; no between-group differences were noted at baseline or 18 months in radial diffusivity, mean diffusivity or fractional anisotropy. ^†p<0.05, 18 months vs baseline for radial diffusivity, mean diffusivity and fractional anisotropy within groups for participants with and without diabetes (p values are shown in Table 2)