White matter microstructural integrity and BOLD fluctuation alterations mediated the effects of insulin resistance on cognitive function in patients with type 2 diabetes mellitus

Aims To explore the neural mechanism of white matter related cognitive dysfunction in patients with type 2 diabetes mellitus. Methods This prospective study between 2016 and 2018 included 55 patients with type 2 diabetes mellitus and 40 participants without type 2 diabetes mellitus. Detailed neuropsychological assessment, clinical and biochemical information, diffusion tensor imaging and resting-state functional MRI were collected. The fractional anisotropy (FA), mean diffusivity (MD) and amplitude of low-frequency fluctuation (ALFF) in white matter were compared between the two groups and then extracted for correlation and mediation analysis with clinical parameters and cognitive assessments. Results The current research showed that three parameters changed in several white matter areas of patients with type 2 diabetes mellitus. Meanwhile, FA in the corpus callosum mediated the effect of insulin resistance on executive function in both two groups. In the group without type 2 diabetes mellitus, ALFF moderated the effect of FA on executive function. Conclusion Patients with type 2 diabetes mellitus showed alterations in structural integrity and activation of white matter, which played a mediating and regulating role in the cognitive impairment caused by insulin resistance.