Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes

Abstract

Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes.

© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Growth rates of total WMVs and GMVs are significantly reduced for type 1 diabetes relative to control subjects; total WMV P < 0.003 (A) and total GMV P < 0.05 (B). Growth rate is defined as the volume at time2 minus the volume at time1 divided by the interval between scans (type 1 diabetes, red line; control subjects, black line).

Figure 2

Cortical regions with significantly reduced growth rates for type 1 diabetes (T1D) relative to control subjects. Colors indicate surface regions where children with diabetes, relative to control subjects, have significantly less growth of cortical volume and SA and significantly more cortical thinning. Regions are displayed on an inflated cortical surface with views of left lateral, left medial, right medial, and right lateral surfaces (gyri, light gray; sulci, dark gray).

Figure 3

Change in total GMV is negatively correlated with the change in instantaneous blood glucose level across scan times for the children with type 1 diabetes (slope = −9.3 mL/[100 mg/dL], P < 0.001).

Figure 4

Cortical regions within the type 1 diabetes group with significant negative correlations to blood glucose level at the time of the scan. Colors indicate surface regions with significant negative correlations of cortical volume, SA, and CT with the change in blood glucose level. Regions are displayed on an inflated cortical surface with views of left lateral, left medial, right medial, and right lateral surfaces (gyri, light gray; sulci, dark gray).