Hailing Zhou ^1* Weiwei Ni ² Weiyin Vivian Liu ³ Li Mingrui ⁴ Shouchao Wei ⁵ Xuanzi Xu ⁶ Shutong Huang ⁷ Lanhui Zhu ² Jieru Wang ¹ Fengling Wen ¹

• ¹ Department of Radiology, Central People's Hospital of Zhanjiang, Zhanjiang, China
• ² Physical Examination Centre, Central People's Hospital of Zhanjiang, Zhanjiang, China, Zhanjiang, Guangdong Province, China
• ³ MRI Research, GE Healthcare (China), Beijing, China
• ⁴ Department of Magnatic Resonance Imaging, Zhanjiang First Hospital of Traditional Chinese Medicine, Zhanjiang, China, Zhanjiang, Guangdong Province, China
• ⁵ Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, China, Zhanjiang, Guangdong Province, China
• ⁶ Department of Teaching and Training, Central People's Hospital of Zhanjiang, Zhanjiang, China, Zhanjiang, Guangdong Province, China
• ⁷ Department of Clinical Laboratory, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong Province, China

Introduction: Type 2 diabetes mellitus (T2DM) accelerates brain aging and disrupts brain functional network connectivity, though the specific mechanisms remain unclear. This study aimed to investigate T2DM-driven alterations in brain functional network connectivity and topology.Methods: Eighty-five T2DM patients and sixty-seven healthy controls (HCs) were included. All participants underwent clinical, neuropsychological, and laboratory tests, followed by MRI examinations, including resting-state functional magnetic resonance imaging (rs-fMRI) and threedimensional high-resolution T1-weighted imaging (3D-T1WI) on a 3.0T MRI scanner. Post-image preprocessing, brain functional networks were constructed using the Dosenbach atlas and analyzed with the DPABI-NET toolkit through graph theory.Results: In T2DM patients, functional connectivity within and between the default mode network (DMN), frontal parietal network (FPN), subcortical network (SCN), ventral attention network (VAN), somatosensory network (SMN), and visual network (VN) was significantly reduced compared to HCs. Conversely, two functional connections within the VN and between the DMN and SMN were significantly increased. Global network topology analysis showed an increased shortest path length and decreased clustering coefficient, global efficiency, and local efficiency in the T2DM group. MoCA scores were negatively correlated with the shortest path length and positively correlated with global and local efficiency in the T2DM group. Node network topology analysis indicated reduced clustering coefficient, degree centrality, eigenvector centrality, and nodal efficiency in multiple nodes in the T2DM group. MoCA scores positively correlated with clustering coefficient and nodal efficiency in the bilateral precentral gyrus in the T2DM group.Discussion: This study demonstrated significant abnormalities in connectivity and topology of largescale brain functional networks in T2DM patients. These findings suggest that brain functional network connectivity and topology could serve as imaging biomarkers, providing insights into the underlying neuropathological processes associated with T2DM-related cognitive impairment.