RESUMEN
Background and Purpose: According to reports, type 2 diabetes (T2D) is a progressive disease. However, no known research has examined the progressive brain structural changes associated with T2D. The purpose of this study was to determine whether T2D patients exhibit progressive brain structural alterations and, if so, how the alterations progress. Materials and Methods: Structural magnetic resonance imaging scans were collected for 81 T2D patients and 48 sex-and age-matched healthy controls (HCs). Voxel-based morphometry (VBM) and causal structural covariance network (CaSCN) analyses were applied to investigate gray matter volume (GMV) alterations and the likely chronological processes underlying them in T2D. Two sample t-tests were performed to compare group differences, and the differences were corrected using Gaussian random field (GRF) correction (voxel-level p < 0.001, cluster-level p < 0.01). Results: Our findings demonstrated that GMV alterations progressed in T2D patients as disease duration increased. In the early stages of the disease, the right temporal pole of T2D patients had GMV atrophy. As the diseases duration prolonged, the limbic system, cerebellum, subcortical structures, parietal cortex, frontal cortex, and occipital cortex progressively exhibited GMV alterations. The patients also exhibited a GMV alterations sequence exerting from the right temporal pole to the limbic-cerebellum-striatal-cortical network areas. Conclusion: Our results indicate that the progressive GMV alterations of T2D patients manifested a limbic-cerebellum-striatal-cortical sequence. These findings may contribute to a better understanding of the progression and an improvement of current diagnosis and intervention strategies for T2D.