Glymphatic system impairment in type II diabetes mellitus adults

Abstract Type 2 diabetes mellitus (T2DM) is associated with multiple systemic complications, including cognitive decline and increased risk of neurodegenerative diseases. The glymphatic system, a brain waste-clearance pathway that can be impaired by sleep disturbances common in T2DM, has not yet been examined in the condition. Therefore, the aim was to evaluate glymphatic system in T2DM subjects using diffusion tensor imaging along the perivascular space (DTI-ALPS) index. A total of 78 T2DM adults and 106 healthy controls underwent brain MRI. Sleep issues were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and cognition with the Montreal Cognitive Assessment (MoCA). Group differences in DTI-ALPS, sleep metrics, and MoCA scores were assessed with analysis of covariance (covariates, age, sex, and BMI). Other covariates (MoCA, ESS, and sleep apnea status) were also included to examine DTI-ALPS differences between groups, in addition to age, sex and BMI. Correlations analyses were performed to assess associations between sleep measures (PSQI and ESS), disease duration, HbA1c levels, and DTI-ALPS indices in T2DM adults. T2DM patients exhibited higher PSQI ( p = 0.03) and ESS ( p = 0.004), reflecting poorer sleep quality and increased daytime sleepiness. MoCA scores were significantly lower in T2DM adults ( p = 0.001), with impairments emerged in visuospatial skills, attention, and language. Also, significantly reduced DTI-ALPS values appeared in T2DM over controls ( p = 0.017), but no significant associations were found between DTI-ALPS index and other measures in T2DM adults. T2DM adults show impaired glymphatic function along with poor sleep quality and daytime sleepiness. The findings indicate that glymphatic dysfunction, potentially-driven by metabolic, vascular, and sleep-related disturbances may exacerbate cognitive deficits in T2DM adults.