Abstract Body

It has been increasingly appreciated that chronic exposure to hyperglycemia is detrimental to the brain, particularly during the critical periods of growth and development in young children. The Diabetes Research in Children Network conducted a longitudinal study focused on neuroanatomical and cognitive consequences of type 1 diabetes (T1D). Over six years of study, we conducted unsedated MRI, cognitive testing batteries, and continuous glucose monitoring assessments in 144 children with diabetes and 72 age-matched controls, beginning at the age of 4-9; compared anatomical and cognitive outcomes between groups; and within the T1D group, correlations with measures of glycemia.

Total brain, gray and white matter volumes, and full-scale and verbal intelligence quotients were lower in the T1D group at all assessment points, and rates of growth of cortical and subcortical gray and white matter were consistently slower in T1D children over this time period spanning childhood and early puberty. Within the T1D group, brain volumes and cognitive scores were negatively correlated with higher CGM-measured glucose levels and a calculated lifetime A1c index. Resting-state fMRI demonstrated increased functional connectivity in executive function control areas in the T1D group, suggesting a mechanism to compensate for the adverse effects of dysglycemia to maintain cognitive and behavioral performance.

The need for improved control of hyperglycemia during the developmental window of childhood and puberty is clear. A recently completed six-month pilot study utilizing automated delivery systems in adolescents with T1D may help to determine the potential impact of improved short-term glycemic control on these critical anatomic and cognitive outcomes.

Abstract Body

AIM: To investigate the effect of acute hyperglycemia on brain connectivity in adolescents with type 1 diabetes.

RESEARCH AND DESIGN METHODS: Fifteen adolescents with type 1 diabetes (14.93 ± 1.87 years), and 20 healthy controls (14.4 ± 2.82 years) performed functional MRI (fMRI) sessions. Participants with type 1 diabetes performed the first session in euglycemia and the second session in hyperglycemia (20 mmol/L [360 mg/dL]). Blood glucose was not manipulated in the control group.

All participants also performed structural MRI scan to evaluate grey and white brain matter and to serve as template for fMRI.

The trial was registered on 15 th June 2017 at clincaltrials.gov, the trial number: NCT03188757, and was approved by National Medical Ethics Committee 0120–476/2017/2.

RESULTS: Gray matter volume (p < 0.005) and cortical surface area were significantly reduced

(p < 0.05) in participants with type 1 diabetes. Fractional anisotropy was significantly increased (p < 0.05), radial and axial diffusivity were significantly decreased (p < 0.05) in participants with type 1 diabetes.

Brain connectivity was significantly increased (p < 0.002) in group with type 1 diabetes. However, during acute hyperglycaemia, it was reduced (p < 0.002) as compared to euglycemia.

CONCLUSIONS: The proposed compensatory mechanism of increased brain connectivity in adolescents with type 1 diabetes fails during acute hyperglycaemia, with possible deleterious effect on executive functions.