Altered brain function and structure in youth-onset type 2 diabetes

Abstract Objective Despite the aggressive clinical trajectory of youth-onset type 2 diabetes (Y-T2D) and consistent evidence of cognitive dysfunction and poor brain health in adults with T2D, the impact of Y-T2D on brain function and structure is understudied. Design This study aimed to characterize brain function and structure in a cross-sectional sample of young people with Y-T2D and compare these brain attributes to peers with obesity alone (OB) or healthy weight (HW) without T2D. Methods Brain structure and function were measured via magnetic resonance imaging. Functional connectivity was estimated with a seed-to-voxel analysis, and gray matter (GM) volume differences explored between groups. Results Forty young adult participants were included (Y-T2D: n=12, mean [±SD] age 25.0±7.2 years, diabetes duration 6.5±6.7 years; OB: n=8, age 19±1.6 years; HW: n=20, age 22.9±4.1 years). The Y-T2D group showed stronger functional connectivity between the salience network and default mode network, compared to both the OB and HW groups (p<0.05 for all, respectively). The Y-T2D group had reduced GM volume in regions associated with executive functioning, language, and visual processing relative to the OB and HW groups (p<0.001 for all, respectively). Conclusions Y-T2D is associated with distinct alterations in brain function and structure, providing evidence of potentially compromised brain health in this clinical population.