Some patients with type 2 diabetes mellitus (T2DM) progress towards mild cognitive impairment (MCI), while some patients can always maintain normal cognitive function. Network topologic alterations at global and nodal levels between T2DM individuals with and without cognitive impairment may underlie the difference.To investigate the topological alterations of the whole-brain white matter (WM) structural connectome in T2DM patients with and without MCI and characterize its relationship with disease severity.Cross-sectional and prospective study.Forty-four (63.6% females) T2DM patients, 22 with mild cognitive impairment (DM-MCI) and 22 with normal cognition (DM-NC), and 34 (58.8% females) healthy controls (HC).3 T/diffusion tensor imaging.Graph theoretical analysis was used to investigate the topological organization of the structural networks. The global topological properties and nodal efficiency were investigated and compared. Relationship between network metrics and clinical measurements was characterized.Student's t-test, chi-square test, ANOVA, partial correlation analyses, and multiple comparisons correction.The global topological organization of WM networks was significantly disrupted in T2DM patients with cognitive impairment (reduced global and local efficiency and increased shortest path length) but not in those with normal cognition, compared with controls. The DM-MCI group had significantly decreased network efficiency compared with the DM-NC group. Compared with controls, decreased nodal efficiency was detected in three regions in DM-NC group. More regions with decreased nodal efficiency were found in the DM-MCI group. Altered global network properties and nodal efficiency of some regions were correlated with diabetic duration, HbA1c levels, and cognitive assessment scores.The more disrupted WM connections and weaker organized network are found in DM-MCI patients relative to DM-NC patients and controls. Network analyses provide information for the neuropathology of cognitive decline in T2DM patients. Altered nodal efficiency may act as potential markers for early detection of T2DM-related MCI.1 TECHNICAL EFFICACY: Stage 2.© 2021 International Society for Magnetic Resonance in Medicine.