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Context: Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer disease (AD). However, no biomarkers are available for early identification of patients with T2DM 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.
Objective: This study aimed to determine whether mitochondrial function in peripheral blood mononuclear cells (PBMCs) of patients with T2DM-CI was altered and if these alterations could be used as biomarkers.
Methods: 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 quantitative polymerase chain reaction. The correlations and diagnostic accuracy were assessed using the Spearman correlation coefficient or receiver operating characteristics analysis, respectively.
Results: We found significant changes in mitochondrial function in PBMCs of patients with AD compared with controls (all P < .05), which were not found in T2DM-CI. However, mtDNA content and SIRT1 mRNA expression were lower in PBMCs of patients with T2DM-CI, while miR-34a-5p expression was higher than in patients with T2DM-nCI (all P < .05). A combination of SIRT1 and miR-34a-5p demonstrated excellent discrimination between T2DM-CI and T2DM-nCI (area under the curve = 0.793; sensitivity: 80.01%; specificity: 78.46%). Furthermore, correlation analysis revealed a link between miR-34a-5p expression and hyperglycemia in T2DM-CI.
Conclusion: Our findings revealed that there was an alteration of mitochondria at the peripheral level in patients with T2DM-CI. SIRT1 combined with miR-34a-5p in PBMCs performed well in identifying patients with T2DM-CI and may be a promising biomarker.
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http://dx.doi.org/10.1210/clinem/dgad562 | DOI Listing |
Sci Rep
January 2025
Department of MRI, Shaanxi Provincial People's Hospital, Xi'an, China.
Early detection of cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) is important for preventive measures due to the lack of effective treatments. The purpose of this study is to investigate the relationship between enlarged perivascular space in the hippocampus (H-EPVS) and cognitive performance in patients with T2DM, and to determine whether it can serve as an imaging marker for cognitive dysfunction. 66 T2DM patients with cognitive impairment (T2DM-CI) and 71 T2DM patients with normal cognitive function (T2DM-NC) underwent cranial MRI scans and comprehensive neuropsychological assessments.
View Article and Find Full Text PDFACS Chem Neurosci
February 2025
Department of International Medical, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road 373, Hefei 230001, Anhui, China.
The dysregulation of T cell differentiation was associated with cognitive impairment. Recently, the peripheric β-secretase (BACE1) has been suggested as a regulator of T cell differentiation, which was increased in both cognitive impairment (CI) and type 2 diabetes mellitus (T2DM) in CI patients. However, the relationship between T cell dysfunction and CI remains unclear.
View Article and Find Full Text PDFNutr Diabetes
November 2024
Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, 710038, Shaanxi, China.
Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
August 2023
Department of Neurology, Affiliated Hospital of Putian University, Putian Fujian 351100.
Objectives: The intestinal microbial characteristics of patients with simple cerebral infarction (CI) and CI complicated with Type 2 diabetes mellitus (CI-T2DM) are still not clear. This study aims to analyze the differences in the variable characteristics of intestinal flora between patients simply with CI and CI-T2DM.
Methods: This study retrospectively collected the patients who were admitted to the Affiliated Hospital of Putian University from September 2021 to September 2022.
J Clin Endocrinol Metab
February 2024
Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Context: Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer disease (AD). However, no biomarkers are available for early identification of patients with T2DM with cognitive impairment (T2DM-CI). Mitochondrial dysfunction is linked to AD.
View Article and Find Full Text PDF