2型糖尿病共病抑郁多模态磁共振脑改变与胰岛素抵抗的相互关系及机制研究

The prevalence of type 2 diabetes comorbid depression (T2DD) is increasing, which leads to poor compliance with treatment recommendations, increased disability and mortality of diabetic patients, and brings heavy social burden. However, the neurological mechanism of T2DD remains unclear. Our preliminary studies found the impairment of the functional connectivity between left hippocampus and bilateral precuneus in T2DD by using resting-state MR, and the significant different brain regions was negatively correlated with insulin resistance (IR). Therefore, we hypothesized that IR plays a potential important role in the neuropathogenesis of T2DD. The present study aimed to systematically explore the cerebral structural and functional alterations and multimodal MRI data fusion in T2DD by using multimodality MRI such as 3 dimensional T1 weighted image, high resolution diffusion tensor imaging, resting-state functional MRI and 3 dimensional arterial spin labeling technique. And then analyze the correlation between the abnormal patterns of the cerebral imaging and IR in T2DD, elucidate the relationship and mechanism between IR and multimodal cerebral MR abnormalities of T2DD. This project will contribute to understand the role of IR in the pathophysiology of T2DD, and to provide a new insight for elucidating the pathogenesis of T2DD and valuable objective imaging biomarkers for early diagnosis and early intervention for T2DD. The findings will have important scientific significance and social values.

2型糖尿病共病抑郁（type 2 diabetes comorbid depression，T2DD）患病率不断升高，导致糖尿病患者治疗依存性差和致残率、致死率增加，带来沉重社会负担。但其神经机制仍不清楚。本课题组前期以静息态fMRI对T2DD进行了预实验, 发现T2DD患者海马与楔前叶间功能连接受损, 且与胰岛素抵抗（insulin resistance，IR）呈负相关。因此，本项目假设IR是参与T2DD神经机制的潜在重要因素，拟采用多模态MRI技术从脑结构、功能改变及多模态数据融合等多方面探讨T2DD的脑影像异常模式，并检测外周血IR指数，分析其与脑改变的相互关系, 力图阐明IR与T2DD多模态脑改变的关系及机制。本研究有助于理解IR在T2DD神经病理生理过程中的作用，为阐明T2DD的神经病理生理机制提供新思路, 为T2DD的早诊断、早干预提供客观依据, 具有重要科学意义和社会价值。

2型糖尿病共病抑郁（T2DD）患病率不断升高，导致糖尿病患者治疗依存性差和致残率、致死率增加，带来沉重社会负担，但其神经机制仍不清楚。本课题组前期以静息态功能磁共振（rs-fMRI）对T2DD进行了预实验, 发现T2DD患者海马与楔前叶间功能连接受损, 且与胰岛素抵抗（IR）呈负相关。本项目假设IR是参与T2DD神经机制的潜在重要因素，采用多模态MRI技术从脑结构、功能改变等多方面探讨T2DD的脑影像异常模式，并检测外周血IR指数，分析其与脑改变的相互关系。结果发现：1. 相较于健康对照组，T2DM患者多个关键脑区间功能连通性明显紊乱，还存在小脑亚区与大脑多个核心脑区间功能连接异常，表明T2DM患者存在静息态脑功能受损。2. T2DD组与T2DM非抑郁组均存在双侧楔前叶、后扣带回和海马的神经活动异常，但T2DD组存在更显著的自发脑活动异常，其中左侧前扣带回局部脑功能活动同步性与胰岛素抵抗指数（HOMA2-IR）相关。另外，基底神经节区的多个脑区的DC值可能是鉴别T2DD组与T2DM非抑郁组的潜在良好指标。3. T2DM患者多个关键脑区的脑皮层厚度存在异常，且右侧岛叶和额下回的体积缩小在伴有IR的T2DM比不伴IR 的T2DM更明显，其中T2DM-IR组左侧岛叶体积减小的同时还伴有自发神经活动的减弱。本研究以IR为研究切入点，以功能磁共振联合结构磁共振技术，结合认知神经心理量表及血液指标变化，进行了系统地分析和研究，为进一步揭示和阐明T2DD的神经病理生理机制提供了新的思路, 为T2DD的早诊断、早干预提供了客观影像学依据, 为该技术在临床上的推广应用提供了科学基础，具有重要科学意义和社会价值。