Chronic hyperglycaemia may be detrimental to developing brain
Children with early-onset type 1 diabetes (T1D) and poor glycaemic control have a slower growth of brain regions associated with sensory processing and cognition compared with nondiabetic controls, according to a longitudinal study of brain growth by the DirecNet*.
Growth of total cortical and subcortical white matter, as well as grey matter, was slower in children with T1D vs controls at all timepoints. Grey matter regions such as the frontal, temporal, subcortical, and occipital cortex showed less growth as did white matter areas like the temporal, parietal, and occipital regions in the brain of children with T1D (p<0.05 family wise error [FWE]-corrected for both). [ADA 2019, abstract 209-OR]
The occipital-cerebellar and basal ganglia regions appeared to be the most affected, with regions of slower growth linked to higher HbA1c values.
The differences are related to disease-long measures of dysglycaemia, said co-principal investigator Dr Nelly Mauras from the Division of Endocrinology, Diabetes & Metabolism at Nemours Children’s Health System in Jacksonville, Florida, US during a news briefing at ADA 2019.
“The higher the HbA1c for life [measured from the time of diagnosis], the lower the [grey matter and white matter] volumes,” she emphasized. “These data suggest that continued exposure to chronic hyperglycaemia may be detrimental to the developing brain and cognition during this critical period of rapid brain maturation.”
Despite the advent of better therapies for T1D, maintenance of near-normal glucose control in young children with hyperglycaemic episodes remains to be a challenge due to parental fears of hypoglycaemic events, which could bring about a spectrum of symptoms ranging from altered cognitive function to seizures, or coma, when severe.
“Hyper- and hypoglycaemia, depending on age and severity, can lead to altered brain structure and cognitive function, particularly in the young developing brain,” said Mauras. However, the extent to which glycaemic exposure adversely impacts the developing brain in young children with early-onset T1D remains to be fully understood.
Mauras and her team sought to investigate whether there are differences in the brain of children with T1D (n=138) vs age-matched controls without diabetes (n=67) followed for 5 years, and whether neuroanatomical changes correlated with long-term exposure to hypo- and hyperglycaemia. A quarter of those in the control group were siblings of the children with T1D.
At baseline, mean age of the children was 7 years, mean HbA1c was 7.9 percent, and median diabetes duration was 2.5 years. Structural MRI was done at baseline, at 18 months, and 2.9 years after the second visit. Voxel-based morphometry was used to determine white matter and grey matter volumes in the children’s brain regions. HbA1c measurements and continuous glucose monitoring were performed every 3 months for 18 months.
When cognitive function was evaluated in this same cohort, those with T1D had persistent deficits on verbal IQ and vocabulary vs the nondiabetic children. [ADA 2019, abstract 1346-P]
“Again, [this is] strongly associated with hyperglycaemia,” noted Mauras. “Longitudinal follow-up of this cohort will continue [for us] to better elucidate the developmental changes in the brain of these children over time.”
Whether these apparent differences can be reversed with scrupulous metabolic control and automated insulin delivery systems is now being actively investigated, she concluded.
*DirecNet: Diabetes Research in Children Network