Topological Property Impairments of Brain Functional Network in Newly-Onset Overweight/Obese Patients with Type 2 Diabetes Mellitus.

Purpose: Obesity can exacerbate metabolic dysfunction in patients with type 2 diabetes mellitus (T2DM), and the degree of various injuries to our body cannot be fully controlled. However, research on early brain function changes in overweight/obese patients with T2DM is not yet perfect. Herein, we studied the topological structure of brain networks and cognitive function alterations in newly-onset overweight/obese T2DM patients. Methods: To investigate the changes in topological structure, we collected clinical data, cognitive scales, and resting-state functional magnetic resonance imaging (fMRI) data from 32 patients with newly-onset overweight/obese T2DM and 27 normal controls (NCs). The topological structure of the constructed network, derived from preprocessed fMRI data, was extracted and analyzed using graph theory methods by GRETNA. The relationships between changes in topological structure and clinical data as well as neurocognitive test scores in patients with newly-onset overweight/obese T2DM were analyzed. Results: Within the set threshold range, both newly-onset T2DM and NC groups had global small-world (δ) values >1.1, but the T2DM group showed lower δ values at each threshold. Compared to NC, T2DM had decreased δ (P = 0.0423, T = -2.079), global efficiency (Eglob) (P = 0.0312, T = -2.212), and increased characteristic path length (Lp) (P = 0.0253, T = 2.301). After multiple comparison corrections, local topological metrics showed no significant inter-group differences. For the sake of prudence, we employed a significance reference threshold of p < 0.005 for uncorrected analyses. Through exploratory investigation, we identified that, without multiple comparison corrections, there were inter-group nodal differences in specific brain regions for the metrics including nodal degree centrality (Dc), nodal clustering coefficient (NCp), and nodal local efficiency (NLe). Network-based statistic found no aberrant connections (P > 0.05). In the T2DN group, a positive correlation was observed between the Dc of left inferior parietal angular gyrus and BMI (P < 0.05). Conclusion: The functional networks of patients with newly-onset T2DM have changes in network efficiency and brain region function. Brain function damage may exist in the early stage of overweight/obese T2DM. This study provides a new thought for the neurobiological mechanism of early brain function damage in overweight/obese T2DM. It is worth noting that the findings of this study suggest that the combined metabolic burden resulting from the coexistence of T2DM and overweight/obesity may jointly participate in mediating alterations in brain networks. However, constrained by the study design, this study failed to independently distinguish the specific effects of obesity. In the future, it is still necessary to conduct refined analyses stratified by BMI to further disentangle the independent and interactive effects of obesity and hyperglycemia on brain structure and function.