The relationship between brain perfusion and structure in youth with obesity, with and without type 2 diabetes: A pilot study

Neurocognitive decline, dementia, and stroke are associated with obesity and type 2 diabetes (T2D) in adults. Youth-onset T2D and obesity are occurring more frequently, increasing the risk of earlier onset brain-related morbidity. Emerging evidence has demonstrated global and regional changes in gray matter volume (GMV) and cerebral blood flow (CBF) in youth with T2D and obesity as well. Understanding brain pathophysiology in youth-onset T2D and obesity requires more complex and multi-modal investigation of the brain, such as integration of brain structure and perfusion. Twenty youth with T2D and nineteen age, race, sex, and body mass index (BMI) similar youth with obesity and normal glycemic control (obese controls) underwent brain MRI to examine GMV (structure) and CBF (perfusion). Voxel-wise analysis was used to examine association between GMV and CBF in all study participants using a linear model. Clusters of voxels with significant model coefficients were determined at p < 0.05 with adjustment for multiple comparisons. Additionally, a systematic algorithm was used to identify clusters of voxels with median effect size exceeding a threshold (f² > 0.15) for each model coefficient. Effect size was represented by Cohen's f² calculated voxel-wise for each model term. A significant and positive relationship between CBF (perfusion) and GMV (structure) among youth with obesity, with and without T2D, was demonstrated in several clusters encompassing the calcarine, cuneus, precuneus, occipital, fusiform, lingual, right insula, and right precentral brain regions (p < 0.05). Effect size analysis yielded suprathreshold voxel clusters for the interaction coefficient in widespread anatomical regions, including the temporal, precuneus, frontal, occipital, lingual, and insular regions, indicating brain regions where the relationship between GMV and CBF differed by group (T2D vs obese controls). Results of this pilot study identified several brain regions with a significant positive relationship between CBF and GMV suggesting that brain perfusion and structure may be coupled in youth with obesity, with and without T2D. Utilization of obese controls revealed brain regions where the relationship between cerebral perfusion and brain structure may be impacted by T2D.