Blood sugar without proper control harms cognition and brain development over period of time in children

Continuous exposure to chronic high blood sugar or hyperglycaemia is detrimental to the developing brain and cognition in children, according to data from Diabetes Research in Children Network (DirecNet).

Optimum blood sugar control is useful for all diabetes patients but maintaining blood sugar levels within accepted treatment norms are equally important in children with diabetes.

Poor blood sugar control and early-onset type 1 diabetes in children is associated with slower growth of brain regions involved in cognition and sensory processing compared with children without the condition, revealed results presented at the American Diabetes Association (ADA) 2019 Scientific Sessions.

The study found that the growth of grey matter, as well as the cortical and subcortical white matter, was slower in children having type 1 diabetes versus controls. The grey matter regions affected include frontal, temporal, subcortical, and occipital cortex. The white matter areas affected include temporal, parietal, and occipital regions. The occipital-cerebellar and basal ganglia regions appeared to be the most affected, with regions of slower growth linked to higher HbA_1c values.

Nelly Mauras, chief, Division of Endocrinology, Diabetes, & Metabolism, Nemours Children's Health System, Jacksonville, Florida, and colleagues 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 HbA_1c 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. HbA_1c measurements and continuous glucose monitoring were performed every 3 months for 18 months.

When the cognitive function was evaluated in this same cohort, those with T1D had persistent deficits on verbal IQ and vocabulary vs the nondiabetic children.

Key findings of the study include:

• Children with type 1 diabetes had slower growth of total cortical and subcortical gray and white matter areas, which are involved in sensory processing and cognition, compared with the control group.


• The occipital-cerebellar and basal ganglia regions appeared to be most vulnerable to the effects of type 1 diabetes in this pediatric population.


• These regions of slower growth were associated with higher cumulative hyperglycemic exposure, as measured by lifetime HbA1c from the time of diagnosis of type 1 diabetes.


• The higher [the] HbA1c for life, the lower the [brain] volumes.

“The higher the HbA_1c for life [measured from the time of diagnosis], the lower the [grey matter and white matter] volumes,” emphasized Dr. Mauras. “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.

“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.