Letter to the Editor
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2025; 16(7): 107406
Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.107406
Breaking the diabetes-depression cycle: Exploring shared mechanisms, neuroinflammation, and emerging interventions for metabolic-mood comorbidities
Cheng Luo, Xian-Mei Yu, Mei-Qi Zeng, Cheng-Zheng Duan, Shi-Yu Xu, Chun-Yan Zhu, Zhi-Gang Zheng, Da Sun, Jian Fang, Dong-Juan He
Cheng Luo, Cheng-Zheng Duan, Shi-Yu Xu, Chun-Yan Zhu, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Xian-Mei Yu, Dong-Juan He, Department of Endocrinology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Mei-Qi Zeng, Zhi-Gang Zheng, Department of Ophthalmology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Da Sun, Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325000, Zhejiang Province, China
Jian Fang, Department of Hepatobiliary Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Co-first authors: Cheng Luo and Xian-Mei Yu.
Co-corresponding authors: Jian Fang and Dong-Juan He.
Author contributions: Luo C and Yu XM contributed to conceptualization and writing of the original draft, they contributed equally as co-first authors; Zeng MQ and Duan CZ contributed to formal analysis and data validation; Xu SY and Zhu CY contributed to methodology and investigation; Zheng ZG and Sun D contributed to supervision and project administration; Fang J and He DJ contributed to reviewing, editing, and final approval of the manuscript, they contributed equally as co-corresponding authors; and all authors participated in drafting the manuscript and have read, contributed to, and approved the final version of the manuscript.
Supported by the Quzhou Science and Technology Plan Project funded by the Quzhou Municipal Science and Technology Bureau, No. 2022K67, No. 2022K69, and No. 2024K076.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Dong-Juan He, MD, Chief Physician, Deputy Director, Department of Endocrinology, The Second People’s Hospital of Quzhou, No. 338 Xin’an Avenue, Qujiang District, Quzhou 324002, Zhejiang Province, China. hedongjuan1247@wmu.edu.cn
Received: March 24, 2025
Revised: April 9, 2025
Accepted: May 15, 2025
Published online: July 15, 2025
Processing time: 114 Days and 23.7 Hours
Core Tip

Core Tip: Type 2 diabetes mellitus and depression share a bidirectional relationship driven by immune inflammation, gut-brain axis dysfunction, metabolic abnormalities, and neuroendocrine dysregulation. Chronic low-grade inflammation, insulin resistance, gut microbiota imbalance, and overactivation of the hypothalamic-pituitary-adrenal axis contribute to both conditions. Emerging treatments targeting these shared mechanisms include anti-inflammatory therapies, gut microbiota modulation, regulation of the hypothalamic-pituitary-adrenal axis, and metabolic interventions such as glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. A multidisciplinary, integrative approach is essential for effective management, emphasizing the need for comprehensive metabolic-mental health strategies to improve patient outcomes and quality of life.