Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes

Abstract

Studies of brain structure in type 1 diabetes (T1D) describe widespread neuroanatomical differences related to exposure to glycemic dysregulation in adults and adolescents. In this study, we investigate the neuroanatomical correlates of dysglycemia in very young children with early-onset T1D. Structural magnetic resonance images of the brain were acquired in 142 children with T1D and 68 age-matched control subjects (mean age 7.0 ± 1.7 years) on six identical scanners. Whole-brain volumetric analyses were conducted using voxel-based morphometry to detect regional differences between groups and to investigate correlations between regional brain volumes and measures of glycemic exposure (including data from continuous glucose monitoring). Relative to control subjects, the T1D group displayed decreased gray matter volume (GMV) in bilateral occipital and cerebellar regions (P < 0.001) and increased GMV in the left inferior prefrontal, insula, and temporal pole regions (P = 0.002). Within the T1D group, hyperglycemic exposure was associated with decreased GMV in medial frontal and temporal-occipital regions and increased GMV in lateral prefrontal regions. Cognitive correlations of intelligence quotient to GMV were found in cerebellar-occipital regions and medial prefrontal cortex for control subjects, as expected, but not for the T1D group. Thus, early-onset T1D affects regions of the brain that are associated with typical cognitive development.

Figure 1

Sagittal (left) and axial (right) three-dimensional renderings of clusters of significant differences between T1D and control subjects. Increased GMV in lateral temporo-frontal regions in T1D relative to control subjects (red cluster, P < 0.01) was also found to be associated with higher HbA_1cD_X. Decreased GMV in occipital regions and cerebellum in T1D relative to control subjects (yellow cluster, P < 0.001) was found to be associated with higher HbA_1cAUC_6% and higher mean glucose.

Figure 2

Significant GMV clusters from whole-brain regression analysis of glycemic measures in the T1D group (height threshold of T = 1.66, cluster extent threshold of P < 0.05, and corrected for FWE and nonstationary smoothness). Clusters are overlaid on the average GM template. HbA_1cAUC_6% (−) (P < 0.001), T1D duration (−, GMV) (P = 0.001), T1D duration (−, WMV) (P < 0.001), HbA_1cD_X (+) (P = 0.01), mean BG (−) (P = 0.007), and mean BG (+) (P = 0.03).

Figure 3

Regions with significant correlations between IQ and GMV. Top: Clusters from whole-brain regression analysis of IQ in the control group (height threshold of T = 1.66, cluster extent threshold of P < 0.05, and corrected for FWE and nonstationary smoothness). Bottom: Conjunction regions with IQ-GMV correlations in control subjects and glycemic-GMV correlations in T1D. Color denotes glycemic variable/contrast: T1D duration (−) (blue), mean glucose (−) (green), control >T1D (red), overlap (yellow). Clusters are overlaid on the average GM template.