Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2025; 16(8): 106664
Published online Aug 15, 2025. doi: 10.4239/wjd.v16.i8.106664
Higher glycated hemoglobin amplifies the effect of apolipoprotein E epsilon 4-related cognition and olfaction impairments in type 2 diabetes
Ya-Rong Wang, Yang Gao, Yan-Chao Liu, Zhi-Peng Xu, Yu-Ying Wang, Hai-Bo Xu, Jian-Zhi Wang, Yao Zhang
Ya-Rong Wang, Yao Zhang, Department of Endocrinology, Li-Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Hubei Province, China
Yang Gao, Hai-Bo Xu, Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
Yan-Chao Liu, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Zhi-Peng Xu, Yu-Ying Wang, Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Jian-Zhi Wang, Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Co-first authors: Ya-Rong Wang and Yang Gao.
Co-corresponding authors: Jian-Zhi Wang and Yao Zhang.
Author contributions: Zhang Y, Wang JZ designed the research and wrote the manuscript; Wang YR, Gao Y, Liu YC, Xu ZP, Wang YY, Xu HB recruited the patients and collected blood samples; Wang YR and Gao Y performed the experiments, performed the statistical analysis; Wang YR contributed to data interpretation and manuscript editing; Zhang Y and Wang JZ was the guarantor of this work and has full access to all the data in the study, and took responsibility for the integrity of the data and accuracy of the data analysis; All authors read and approved the final manuscript.
Supported by the China Postdoctoral Science Foundation General Program, No. 2024M762504; and the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 2023 LYYYGZRP0004.
Institutional review board statement: The Medical Ethics Committee approved the study protocol (No. 2013-S071), Tongji Medical College, Huazhong University of Science and Technology.
Informed consent statement: All participants had provided written informed consent.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: All data are available in the manuscript or the supplementary materials. Other data supporting the findings of this study are available from the corresponding author, prof. Zhang Y (zhangyaodoc@163.com), upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yao Zhang, Doctor, Department of Endocrinology, Li-Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Qiaokou District, Wuhan 430077, Hubei Province, China. zhangyaodoc@163.com
Received: March 4, 2025
Revised: April 30, 2025
Accepted: July 4, 2025
Published online: August 15, 2025
Processing time: 163 Days and 17.4 Hours
Core Tip

Core Tip: This study explores how the apolipoprotein E epsilon 4 (APOE4) genotype and glycated hemoglobin (HbA1c) levels influence cognitive and olfactory performance in individuals with type 2 diabetes mellitus. The findings suggest that APOE4 is linked to both cognitive and olfactory deficits, and that elevated HbA1c levels further intensify these effects. Rather than serving as a mediator, HbA1c modifies the relationship, strengthening the adverse impact of APOE4. These results indicate that both APOE4 and poor glycemic control contribute to neurofunctional decline, underscoring the importance of early intervention in at-risk diabetic populations.