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The aim of this study was to explore the topological alterations of the brain functional network in type 2 diabetes mellitus (T2DM) patients with and without mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory approaches. In total, 27 T2DM patients with MCI, 27 T2DM patients without MCI, and 27 healthy controls (HCs) underwent rs-fMRI scanning. The whole-brain functional network was constructed by thresholding the Pearson’s correlation matrices of 90 brain regions. The topological organization of the constructed networks was analyzed by using graph theory approaches. The global and nodal properties of the participants in the three groups were compared by using one-way ANOVA as well as  post hoc  Tukey’s  t -tests. The relationships between the altered topological properties and clinical features or scores of neuropsychological tests were analyzed in T2DM patients with MCI. At the global level, the global and local efficiency of the patients in the T2DM with MCI group were significantly higher than that of participants in the HCs group, and the length of the characteristic path was significantly lower than that of the participants in the HCs group ( p  &amp;lt; 0.05). No significant difference was found among the other groups. At the nodal level, when compared with T2DM patients without MCI, T2DM patients with MCI showed significantly increased nodal centrality in four brain regions, which were mainly located in the orbitofrontal lobe and anterior cingulate gyrus (ACG) ( p  &amp;lt; 0.05). No significant difference was found between the T2DM patients without MCI and HCs. Moreover, nodal degree related coefficient ( r  = −0381,  p  = 0.050) and nodal efficiency ( r  = −0.405,  P  = 0.036) of the ACG showed a significant closed correlation with the scores of the digit span backward test in the T2DM patients with MCI. Our results suggested that the increased nodal properties in brain regions of the orbitofrontal lobe and ACG were biomarkers of cognitive impairment in T2DM patients and could be used for its early diagnosis. The global topological alterations may be related to the combination of MCI and T2DM, rather than any of them.

Topological Alterations of the Brain Functional Network in Type 2 Diabetes Mellitus Patients With and Without Mild Cognitive Impairment