Regional Brain Structure Alterations in Diabetes but Not Prediabetes

Diabetes (DM) affects brain volume and white matter hyperintensity (WMH), but whether regional gray matter volume (GMV) and tract-specific WMH progress in the prediabetes (PreDM) stage remains unclear.

We investigate brain structural changes across 3 distinct glycemic states.

We analyzed 512 participants (122 with DM, 109 with PreDM, and 281 controls) using advanced neuroimaging techniques. High-resolution structural T1-weighted magnetic resonance images and FLAIR (fluid-attenuated inversion recovery) images were acquired, complemented by cognitive assessments, grip strength measurements, and gait speed testing. We performed correlational analyses to examine the relationships between observed brain changes, cognitive performance, and motor function across different levels of glycemic states.

We found substantial changes in GMV in DM, especially in areas responsible for movement and coordination, including the bilateral cerebellum, right precentral gyrus, and left postcentral gyrus (P < .001 uncorrected with cluster size > 500). These brain changes were associated with decreases in cognitive test scores (Montreal Cognitive Assessment; P = .04), gait speed (P < .05), and right-hand grip strength (P < .05)-effects not seen in the prediabetic group. We observed significantly higher WMH index across 20 tracts in DM brains (P < .05; false discovery rate [FDR]-corrected). Glycemic levels positively correlated with WMH index in multiple tracts (P < .05; FDR-corrected).

This study illuminates DM as a powerful force in cerebral architecture, challenging the notion of a gradual decline beginning in PreDM. These insights not only underscore the critical importance of DM prevention but also hint at the brain's remarkable resilience in the face of early metabolic challenges.