Progressive reduction in basal ganglia explains and predicts cerebral structural alteration in type 2 diabetes

Type 2 diabetes is consistently reported to be associated with reduced gray matter, mainly in the cortical-striatal-limbic networks. However, little is known about how the progression of diabetes affects cerebral gray matter. To investigate, we collected 543 age- and sex-matched participants of nondiabetes, prediabetes, and diabetes. Voxel-based morphometry using a linear trend model was performed to reveal brain regions associated with disease progression. The Granger causal network of structural covariance was used to assess the causal relationships of brain structural alterations according to disease progression. Multivariate pattern analysis was applied for the stage-specific predictions of hyperglycemia. We detected a linear trend of gray matter volume reduction in the basal ganglia with disease progression (P < 0.05, FWER corrected), which caused a reduction in bilateral temporal gyri, frontal pole, parahippocampus, and bilateral posterior cingulate/precuneus volumes. In addition, the gray matter pattern of the basal ganglia could predict patients with diabetes (accuracy 60.12%, p = 0.002). In conclusion, the basal ganglia is the brain area with progressive gray matter reduction as diabetes progress. The reduced volume in the basal ganglia causes widespread gray matter reductions throughout diabetes progression. These findings indicate that the basal ganglia play a key role in diabetes by affecting the cortical-striatal-limbic network.