White matter microstructural integrity in youth with type 1 diabetes

Abstract

Decreased white and gray matter volumes have been reported in youth with type 1 diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter integrity have not been quantitatively assessed during brain development. We performed diffusion tensor imaging, using two complimentary approaches--region-of-interest and voxelwise tract-based spatial statistics--to quantify white matter integrity in a large retrospective study of T1DM youth and control participants. Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT), were estimated through medical records review, HbA(1c) levels, and interview of parents and youth. We found lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history of three or more severe hyperglycemic episodes was associated with reduced anisotropy and increased diffusivity in the superior parietal lobule and increased diffusivity in the hippocampus. These results add microstructural integrity of white matter to the range of structural brain alterations seen in T1DM youth and suggest vulnerability of the superior parietal lobule, hippocampus, and thalamus to glycemic extremes during brain development. Longitudinal analyses will be necessary to determine how these alterations change with age or additional glycemic exposure.

FIG. 1.

ROIs defined on a T2 (left) and fractional anisotropy (right) image. CC, corpus callosum; PLIC, posterior limb of the internal capsule. (A high-quality color representation of this figure is available in the online issue.)

FIG. 2.

A: TBSS results comparing axial diffusivity maps between T1DM and control subjects, which were reduced in T1DM youth compared with control subjects. B: Different severe hyperglycemic categories and control subjects. One-way ANOVA was significant, but none of the pairwise comparisons reached significance. C: Severe hypoglycemic categories and control subjects. One-way ANOVA was significant, but none of the pairwise comparisons reached significance. Green, TBSS skeleton; red, P = 0.05; orange, P = 0.02. (A high-quality digital representation of this figure is available in the online issue.)