Brain functional alterations in type 2 diabetes with obstructive sleep apnea patients: A multicenter resting-state fMRI study.

Objective: This multicenter study aimed to investigate resting-state brain functional alterations in patients with type 2 diabetes mellitus (T2DM) comorbid with obstructive sleep apnea (OSA), and to elucidate the underlying neural mechanisms.

Methods: A total of 139 participants were enrolled from two centers, including 48 healthy controls (HCs), 46 T2DM patients, and 45 T2DM with OSA patients. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to assess brain function using degree centrality (DC), amplitude of low-frequency fluctuation (ALFF), and seed-based functional connectivity (FC). Group comparisons were conducted, and partial correlation analyses were performed with clinical and neuropsychological measures.

Results: Compared with HCs group, the T2DM group showed significantly lower ALFF values in the right parahippocampal gyrus, which were negatively correlated with fasting glucose levels. Compared with the T2DM group, the T2DM with OSA group exhibited significantly lower DC values in the left medial superior frontal gyrus, and lower ALFF values in the bilateral medial superior frontal gyrus and the left middle frontal gyrus. Additionally, FC between the left medial superior frontal gyrus and the left middle frontal gyrus was higher, whereas FC between the left middle frontal gyrus and the right middle temporal gyrus, as well as the right rectus gyrus, was lower. These functional alterations were closely associated with the Montreal Cognitive Assessment (MoCA) scores and oxygen desaturation index (ODI).

Conclusion: The findings reveal widespread brain functional abnormalities in patients with T2DM and in those with comorbid T2DM and OSA, particularly within the frontal and temporal networks. These alterations are strongly associated with hyperglycemia, intermittent hypoxia, and cognitive impairment. These findings offer novel imaging-based insights into the neural mechanisms underlying brain dysfunction in patients with coexisting T2DM and OSA, and underscore the clinical importance of implementing integrated interventions in this population to mitigate the risk of cognitive decline.