Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2025; 16(5): 101473
Published online May 15, 2025. doi: 10.4239/wjd.v16.i5.101473
Impaired efferocytosis by monocytes and monocyte-derived macrophages in patients with poorly controlled type 2 diabetes
Qian-Yun Mao, Hui Ran, Qiu-Yue Hu, Sun-Yue He, Yao Lu, Han Li, Yi-Meng Chai, Zhao-Yin Chu, Xu Qian, Wan Ding, Yi-Xin Niu, Hong-Mei Zhang, Xiao-Yong Li, Qing Su
Qian-Yun Mao, Hui Ran, Qiu-Yue Hu, Yao Lu, Han Li, Yi-Meng Chai, Zhao-Yin Chu, Xu Qian, Wan Ding, Yi-Xin Niu, Hong-Mei Zhang, Xiao-Yong Li, Qing Su, Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
Sun-Yue He, Department of Endocrinology and Metabolism, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 200240, Zhejiang Province, China
Co-first authors: Qian-Yun Mao and Hui Ran.
Co-corresponding authors: Xiao-Yong Li and Qing Su.
Author contributions: Mao QY and Ran H conceived the idea and designed the study; Mao QY and Hu QY performed the research and data analyses; Mao QY, Ran H, Li XY and Niu YX recruited patients; He SY provided the experiment methodology; Lu Y, Qian X and Li H contributed to the study design; Chai YM, Chu ZY, Ding W and Zhang HM analyzed and managed the data and images; Mao QY wrote the manuscript; Su Q, Li XY and Ran H revised the manuscript. All authors had approved the final manuscript for submission. Li XY and Su Q are the guarantors of this work and, as such, had full access to all the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis. Mao QY and Ran H contributed equally to this work as co-first authors. The two co-corresponding authors contributed equally to this study. Prof. Su Q and Li XY are the guarantors of this work and, as such, had full access to all the data in the study and responded to the integrity of the data and the accuracy of the data analysis. In particular, professor Su Q proposed the idea, completed the preliminary experiments and provided advice on experimental ideas and experimental methods. Li XY participated in recruited patients and sample collection. In addition, the two co-corresponding authors provided funding to ensure the study was conducted. Considering the importance of both corresponding authors' contributions, we listed them as co-corresponding authors.
Supported by National Natural Science Foundation of China, No. 81970669, No. 82170835, and No. 82100848; Shanghai Municipal Health Commission, No. 202240107, and No. 20234Y0040; and China Endocrine Metabolism Research Program of Excellence, No. 2023-N-03-05.
Institutional review board statement: Study procedures for human participants were approved by the ethics committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. All participants gave written informed consent prior to enrollment.
Institutional animal care and use committee statement: No animal experiments are performed in this paper.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data sharing statement: No additional data are available.
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: Qing Su, MD, PhD, Professor, Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. suqing@xinhuamed.com.cn
Received: September 16, 2024
Revised: January 8, 2025
Accepted: February 21, 2025
Published online: May 15, 2025
Processing time: 221 Days and 17.3 Hours
Abstract
BACKGROUND

Deficient efferocytosis (i.e., phagocytic clearance of apoptotic cells) by macrophages has been frequently reported in experimental models of type 2 diabetes (T2D).

AIM

To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.

METHODS

Overall, 30 patients with poorly controlled T2D [glycosylated hemoglobin (HbA1c) ≥ 8.0%] and 30 age- and sex-matched control subjects were enrolled in the study. The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining. Macrophage membrane CD14 expression was examined by flow cytometry. Metabolic factors such as 25(OH)D and immune factors such as interleukin-1β were also measured.

RESULTS

The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group. Notably, efferocytosis remained impaired after monocytes differentiated into macrophages. Additionally, the percentages of classical monocytes (CD14++CD16- monocytes) and CD14+ macrophages were significantly lower in the diabetes group. Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level, and that the macrophage efferocytosis index was significantly associated with the percentage of CD14+ macrophages.

CONCLUSION

Impaired efferocytosis was observed in T2D patients, with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages. The efferocytosis index was negatively associated with metrics of glycemic control, and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.

Keywords: Type 2 diabetes; Efferocytosis; Monocyte; Macrophage

Core Tip: This study compared the efferocytosis function of blood monocytes and monocyte-derived macrophages in type 2 diabetes (T2D) patients with poor glycemic control. The results revealed that both monocytes and macrophages exhibited impaired efferocytosis. Additionally, the percentages of classical monocytes (CD14++CD16- monocytes) and CD14+ macrophages were significantly lower in the diabetes group. Multivariate linear regression analysis demonstrated that the monocyte efferocytosis index was independently associated with both the glycosylated hemoglobin level and the macrophage efferocytosis index showed a significant association with the percentage of CD14+ macrophages. These findings suggest that glucotoxicity may impact efferocytosis by reducing CD14 expression on both monocytes and macrophages in T2D patients.