Cognitive Performance and Specific Brain Tract Segmental Alterations are Associated with Glycemic Control and Variability in Pediatric Patients with T1D

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 glycemic goals, with high postprandial excursions. The effects of the excursions on specific relations between cognitive performance and specific brains tract alterations in young patients are yet unknown.

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

Methods: A case-control study included 12-18 years old patients with T1D (N=17, 8 males, diabetes duration of 6·53±4·1 year) and their healthy siblings(N=13). All underwent brain imaging including diffusion tension imaging (DTI) and baseline neurocognitive tests; a 30-hours hospitalization for continuous capillary glucose monitoring along with multiple repeated neurocognitive tests as a function of controlled manipulation of food intake and pre-meal insulin administration so to enable capillary glucose of above 240 mg/dl versus lower than 180 mg/dl.

Results: Mean HbA1c was 8·61±1·26, 8 of them having HbA1c≤8.3. Significant associations were detected between glucose level, HbA1c, and performance in domains of executive functions, inhibition ability, semantic and episodic memory. White matter (WM) analysis demonstrated opposite effects of diffusion coefficients in various regions according to glycemic control, which indicated specific associations between anatomical pathways and cognitive functions, as a function of the group.

Discussion: Worse glycemic control and transient high glucose levels are associated with both lower performance in executive functions and variability in brain architecture in related areas.