Introduction & Objective: Diabetes elevated cognitive impairment risk. Early identification of at-risk diabetes patients is crucial. This study explores exosomal microRNAs (exo-miRNAs) as potential biomarkers for early detection of cognitive impairment in T2DM.
Methods: Small RNA sequencing was conducted on exosomes from adipose tissue of T2DM patients and healthy controls. Mendelian randomization (MR) analysis was employed to detect the causal effect of miRNAs on cognitive impairment. Diagnostic performance of the candidates was tested in serum samples from a training cohort and validated in a multicenter cohort.
Results: Twenty-six miRNAs were significantly upregulated in adipose tissue exosomes of T2DM patients. MR analyses identified three miRNAs (miR-25-5p, miR-584-5p, and miR-625-5p) that were causally linked to impaired cognitive function (β=-0.016~ -0.012, P<0.05) and dementia (OR=1.06~1.12, P<0.05). The panel of these three exo-miRNAs in serum samples exhibited a robust ability to detect dementia in T2DM patients (AUC= 0.82, 95%CI 0.71~0.96), which was further confirmed in an external validation cohort.
Conclusions: The study revealed a causal link between exo-miRNAs and dementia in T2DM, providing a new perspective for early detection and therapeutic targets of cognitive impairment in T2DM.
Y. Bi: None. S. Yang: None. Z. Zhang: None.
