Objective: Cognitive impairment in type 2 diabetes mellitus (T2DM) patients is related to changes in hippocampal structure and function. However, the alternation of hippocampal subfields volumes and their relationship with cognitive function are unclear. This study explored morphological alterations in the hippocampus and its subfields in T2DM patients and their relationship with cognitive function. Methods: Thirty T2DM patients and 20 healthy controls (HCs) were recruited and underwent 3-dimensional, high-resolution T1-weighted sequence (3D-T1) and a battery of cognitive tests. Freesurfer 6.0 was performed to segment the hippocampus into 12 subregions automatically. Then relationships between hippocampal subfield volumes and neurocognitive scale scores in the T2DM group were evaluated. Results: Immediate memory scores on the auditory verbal learning test (AVLT) and Montreal Cognitive Assessment (MoCA) scores in T2DM patients were lower than in the HCs. T2DM patients showed that volumes of the bilateral hippocampus were significantly reduced, mainly in the bilateral molecular layer, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), cornu ammonis 4 (CA4), fimbria, and left subiculum and the right hippocampus amygdala transition area (HATA) compared to HCs. In addition, T2DM patients showed the FINS was negatively correlated with volume of left GC-ML-DG (r = -0.415, P = 0.035) and left CA4 (r = -0.489, P = 0.011); the FBG was negatively correlated with volume of right fimbria (r = -0.460, P = 0.018); the HOMA-IR was negatively correlated with volume of left GC-ML-DG (r = -0.367, P = 0.046) and left CA4(r = 0.462, P = 0.010). Partial correlation analysis found that the volume of right HATA in T2DM group was positively correlated with AVLT (immediate) scores (r = 0.427, P = 0.03). Conclusion: This study showed the volumes of multiple hippocampal subfields decreased and they were correlated with FINS, FBG and HOMA-IR in T2DM patients. We hypothesized that decreased hippocampal subfields volumes in T2DM patients was related to insulin resistance and impaired vascular function. In addition, we also found that abnormal hippocampal subfields volumes were related to memory function in T2DM patients, suggesting that reduced volumes in specific hippocampal subfields may be the potential mechanism of memory dysfunction in these patients.

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