SIRT1 and miR-34a-5p Expression in PBMCs as Potential Biomarkers for Patients With Type 2 Diabetes With Cognitive Impairments

Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer's disease (AD). However, no biomarkers are available for early identification of T2DM patients with cognitive impairment (T2DM-CI). Mitochondrial dysfunction is linked to AD. Silent Information Regulator 1 (SIRT1), which is responsible for regulating mitochondrial biogenesis, and its related miRNAs were also altered in AD.This study aimed to determine whether mitochondrial function in peripheral blood mononuclear cells (PBMCs) of T2DM-CI patients was altered and if these alterations could be used as biomarkers.A total of 374 subjects were enrolled, including AD, T2DM-CI, T2DM-nCI (T2DM without cognitive impairment), and healthy controls. The mitochondrial function was determined using a commercial assay kit. The mitochondrial DNA (mtDNA) content, the expression of SIRT1, and selected miRNAs in PBMCs were measured by qPCR. The correlations and diagnostic accuracy were assessed using the Spearman correlation coefficient or receiver operating characteristics analysis, respectively.We found significant changes in mitochondrial function in PBMCs of AD patients compared to controls (all P < 0.05), which were not found in T2DM-CI. However, mtDNA content and SIRT1 mRNA expression were lower in T2DM-CI patients' PBMCs, while miR-34a-5p expression was higher compared with T2DM-nCI patients (all P < 0.05). A combination of SIRT1 and miR-34a-5p demonstrated excellent discrimination between T2DM-CI and T2DM-nCI (AUC = 0.793; sensitivity: 80.01%; specificity: 78.46%). Furthermore, correlation analysis revealed a link between miR-34a-5p expression and hyperglycemia in T2DM-CI.Our findings revealed that there was an alteration of mitochondria at the peripheral level in T2DM-CI patients. SIRT1 combined with miR-34a-5p in PBMCs performed well in identifying T2DM-CI patients and may be a promising biomarker.