Altered functional connectivity in type 2 diabetes with and without cerebral small vessel disease: a multimodal MRI study

Comorbid type 2 diabetes (T2D) and cerebral small vessel disease (CSVD) cause severe cognitive impairment. Using diffusion tensor imaging (DTI) and functional connectivity (FC), this study identifies non-invasive imaging biomarkers of early functional changes in T2D patients with CSVD. This study retrospectively analyzed T2D patients who were hospitalized in the Endocrinology Department from November 2024 to November 2025. The enrolled patients were divided into the T2D with and without CSVD groups, based on magnetic resonance imaging (MRI). We collected their laboratory indicators of glucose, lipid metabolism, and liver and kidney function, as well as MRI structural and functional imaging. Independent samples t-test, correlation analysis and FC analysis were applied to compare intergroup differences in microstructural properties, neural activity and functional connectivity. The glycated hemoglobin A1c (HbA1c) was an independent risk factor for the occurrence of CSVD in T2D patients ( P = 0.038, OR = 1.7). DTI results showed the Mean Diffusivity (MD) values of T2D with CSVD in the right middle cingulum were higher than those without CSVD group, P = 0.036, and the Anisotropy Mode (MO) values were closer to 0. Based on the cingulum and hippocampus seeds points, voxel-wise FC analysis revealed that the FC of T2D with CSVD patients had significantly reduced in hippocampus, parahippocampal and prefrontal cortex regions (P FDR <0.001). Finally, ROI-wise FC results showed that the zFC values of the left hippocampus, and the edge memory circuit in T2D with CSVD patients were significantly decreased ( P < 0.05). The correlation analysis results showed the T2D with CSVD had a stronger correlation with glycosylated albumin ( r =-0.681, P = 0.010). HbA1c is an independent risk factor for diabetic patients developing CSVD. The combination of DTI with rs-fMRI results can serve as an early imaging biomarker for occult brain cognitive impairment in patients with diabetes combined with CSVD.