Novel Insights into The Associations between Specific Brain Tract Segmental Alterations, Glucose Levels, and Cognitive Performance Among Adolescents with Type 1 Diabetes

Background:
Type 1 diabetes mellitus (T1D) impacts brain function and structure, even among pediatric patients. Despite intensive management and technological interventions, most patients do not achieve glycaemic goals and have high postprandial excursions. The effects of these excursions on specific relations between cognitive performance and specific brain tract alterations in young patients are yet unknown.

Aim:
To assess the association between neurocognitive accomplishments, quantitative parameters of white matter brain architecture, and glycaemic control among adolescents with T1D and healthy siblings of similar age.

Methods:
A case-control study included 12- to 18-year-old patients with T1D (N=17, 8 males, diabetes duration of 6·53±4·1 year) and their healthy siblings(N=13). Participants underwent brain imaging, including diffusion tension imaging (DTI) and baseline neurocognitive tests. All were hospitalized for 30 hours for continuous glucose monitoring and multiple repeated neurocognitive testing as a function of controlled manipulation of food intake and pre-meal insulin administration to enable capillary glucose of >240 mg/dl versus

Results:
Mean HbA1c was 8·61±1·26, eight participants having HbA1c≤8·3. Significant associations were detected between glucose level, HbA1c, and executive function (EF), inhibition ability, and semantic and episodic memory. White matter analysis demonstrated opposite effects of diffusion coefficients in various regions according to glycaemic control, indicating specific associations between anatomical pathways and cognitive performance as a function of the group.

Conclusions:
Worse glycaemic control and transient high glucose levels are associated with lower executive function and variability in brain architecture in related areas.