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Association between red blood cell count and cortical functional connectivity in type 2 diabetes mellitus patients residing at high altitude: resting-state fMRI study in the Tibetan Plateau

Year: 2026

Type: article

Abstract: Background: Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and emotional disturbances, in which the hippocampus and amygdala are key limbic structures. We investigated hippocampal and amygdala functional connectivity (FC) in Tibetan patients with T2DM residing in a high-altitude hypoxic environment and examined associations with clinical and biochemical measures. Methods: We included 87 Tibetan patients with T2DM and 63 healthy controls (HC) from the Tibetan Plateau. Seed-based resting-state FC analysis was used to compare whole-brain hippocampal and amygdala FC between groups. Associations between altered FC and biochemical indices, emotional symptoms, and cognitive performance were assessed using Pearson or Spearman correlation analyses. Results: Compared with HC, Tibetan patients with T2DM showed increased FC between the right hippocampus and the left dorsolateral prefrontal cortex (DLPFC)/superior frontal gyrus and between the left amygdala and the right orbitofrontal cortex (OFC)/right DLPFC. Within the T2DM group, hippocampal FC was positively associated with red blood cell (RBC) count and visuospatial memory scores, whereas amygdala FC was positively associated with visuospatial memory scores and Mini-Mental State Examination scores. Conclusion: Tibetan patients with T2DM showed increased hippocampal and amygdala FC, which was associated with RBC count and memory-related cognitive performance. No significant associations were observed between altered FC and blood glucose measures. These findings characterize limbic-prefrontal connectivity alterations and their clinical associations in this high-altitude Tibetan T2DM cohort.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1931880