Structural alteration of hippocampal subfields in type 2 diabetes mellitus patients with dyslipidemia.

Objective: To explore alterations in hippocampal subfield volumes in type 2 diabetes mellitus (T2DM) patients with dyslipidemia using hippocampal subfield segmentation.

Methods: A total of 99 T2DM patients were prospectively recruited and divided into two groups based on the presence or absence of dyslipidemia: the T2DM dyslipidemia group and the T2DM normal lipidemia group. Additionally, 57 healthy volunteers were recruited as the healthy control (HC) group. General clinical data and cognitive psychological scale scores were collected. Subgroup analyses of T2DM patients were conducted based on the presence or absence of mild cognitive impairment (MCI). Hippocampal subfield volumes were analyzed using a general linear model with post-hoc Bonferroni correction. Significant differential hippocampal subfields were further analyzed in subgroups using the general linear model with post-hoc Bonferroni tests. Partial correlation analyses were performed to assess correlations between subfield-specific volumes and lipid and glucose metabolism indicators, as well as cognitive psychological scale scores. P-values from partial correlation analyses were corrected using the false discovery rate (FDR).

Results: Volumes of the bilateral hippocampal tail, left presubiculum_body, and right subiculum_body were significantly reduced in the T2DM dyslipidemia group compared to both the HC group and the T2DM normal lipidemia group. Post-hoc analyses revealed that the T2DM dyslipidemia group had the smallest hippocampal subfield volumes. Further subgroup analysis showed that T2DM dyslipidemia patients with MCI exhibited the most pronounced volume reductions in the bilateral hippocampal tail and right subiculum_body. After FDR correction, partial correlation analysis indicated that, in the T2DM dyslipidemia group, the left hippocampal tail volume was positively correlated with the Montreal Cognitive Assessment score. In the T2DM dyslipidemia without MCI group, the volume of the right subiculum_body was negatively correlated with fasting insulin levels and the insulin resistance index, but positively correlated with total cholesterol and low-density lipoprotein cholesterol levels. In T2DM patients with normal lipidemia without MCI, the volume of the right subiculum_body was positively correlated with TC levels.

Conclusion: T2DM patients with dyslipidemia, especially those with MCI, exhibit significant atrophy in hippocampal subfield volumes, with correlations observed between lipid levels and hippocampal subfield volume changes. These findings suggest that lipid alterations may play an essential role in hippocampal structural abnormalities and cognitive impairment in T2DM patients. This study provides new insights into the neuropathophysiological mechanisms underlying brain alterations and cognitive decline in T2DM.