Hsa_circ_0015335 as a potential biomarker for cognitive decline in type 2 diabetes mellitus

BackgroundType 2 diabetes (T2DM) is an independent risk factor for accelerated cognitive decline, creating a need for non-invasive biomarkers to diagnose T2DM-related mild cognitive impairment (T2DM-MCI). Circular RNAs (circRNAs), known to regulate T2DM pathophysiology, represent promising candidate biomarkers.ObjectiveWe aimed to assess the relationship between circRNAs levels and cognitive decline in T2DM patients.MethodThis study included 64 patients with T2DM-MCI and 75 patients with T2DM and normal cognition (T2DM-NC). All T2DM-MCI participants completed a 1.5-year follow-up period. Neuropsychological assessments were performed for all participants. Blood levels of circRNA were quantified using real-time quantitative polymerase chain reaction.Results(1) Whole-blood expression of hsa_circ_0015335 was significantly reduced in T2DM-MCI patients compared to T2DM-NC controls. (2) Receiver operating characteristic (ROC) curve analysis demonstrated that hsa_circ_0015335 could differentiate T2DM-MCI from T2DM-NC with an Area Under ROC Curve of 0.722. (3) Lower hsa_circ_0015335 levels showed significant negative correlations with global cognitive function, episodic memory, and executive function scores in T2DM-MCI patients. (4) A significant interaction was observed between reduced hsa_circ_0015335 expression and elevated triglyceride glucose (TyG) index, collectively contributing to global cognitive impairment in T2DM-MCI patients. (5) Mediation analysis revealed that the TyG index significantly mediated the association between baseline hsa_circ_0015335 levels and the rate of global cognitive decline during follow-up.ConclusionsPeripheral blood hsa_circ_0015335 shows potential as a biomarker for T2DM-MCI identification and cognitive decline progression in affected patients. This circRNA may contribute to cognitive impairment pathogenesis in T2DM, potentially through mechanisms involving glucose metabolism dysregulation.