The brain as a target of diabetes complications in children
Abstract
Background and Aims / Part 1
Severe hypoglycemia may affect the developing brain, yet exposure to chronic hyperglycemia may also adversely impact brain development, particularly in children with early-onset T1D. In the Diabetes Research in Children Network, we are studying cognitive and neurodevelopmental consequences of T1D in a cohort of 144 children (initially 4-9 years old), and 70 age-matched non-diabetic controls.
Methods / Part 2
We performed unsedated structural MRI, using contemporary software, and age-appropriate cognitive testing. Lifetime A1c and glucose sensor data were also assessed.
Results / Part 3
We observed significant differences in total brain, gray matter (GM) and white matter (WM) volumes, and altered WM microstructure in T1D compared to controls, and slower brain growth after longitudinal, 18-months follow-up. These differences were highly correlated with metrics of hyperglycemia. Subsequent longitudinal follow-up through puberty shows that children with T1D had slower growth of total cortical and subcortical GM and WM than controls at all time-points; also lower verbal IQ and working memory scores, differences again associated with higher lifetime A1c. Using functional MRI, brain activation patterns showed increased recruitment of executive control areas in T1D, which possibly act to offset diabetes-related impairments in the default mode network (the brain’s “idle “system). We posit these findings may be compensatory mechanisms to facilitate cognitive and behavioral performance.
Conclusions / Part 4
In conclusion, these and other studies demonstrate that hyperglycemia is detrimental to the developing brain during the critical period of rapid brain maturation in children. The impact of improved glycemic control on the brain using artificial pancreas technologies, e.g., is being actively investigated and requires long-term study.