MINI REVIEW article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
This article is part of the Research TopicImmunosenescence and Metabolic Reprogramming in Aging: Mechanistic Insights and InterventionsView all 8 articles
Diabetic Encephalopathy: Metabolic Reprogramming as a Potential Driver of Accelerated Brain Aging and Cognitive Decline
Provisionally accepted
- 1Department of Endocrinology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
- 2Nanjing University of Chinese Medicine, Nanjing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Diabetic encephalopathy (DE) is a serious neurological complication of diabetes and is expressed as progressive decline in cognitive function, emotional disorders, and changes in brain structure. This review brings together the relevant evidence and demonstrates that metabolic reprogramming, the adaptive reconfiguration of the core metabolic pathway in response to hyperglycemia, is a potential driver of accelerated brain aging in DE. The main pathological characteristics are: abnormal brain insulin signaling, resulting in a decrease in neuronal glucose intake and a decrease in mitochondrial oxidative phosphorylation, oxidative stress and neuroinflammation caused by high blood sugar, in which excess reactive oxygen species (ROS), impairs mitochondrial integrity and leads to activation of microglia cells. The impaired mitophagy and the macrophages remove defects and cause the accumulation and energy collapse of the dysfunctional organelles. In addition, it promotes excessive glycolytic flux, lipolysis disorder, lactic acid accumulation, and ceramide-dependent synaptic damage. We further examine shared metabolic mechanisms between DE and neurodegenerative diseases such as alzheimer's disease (AD) and treatment strategies for pathological metabolic reprogramming including GLP-1 receptor agonists, NAD+ boosters, and AMPK activators. This analysis laid the foundation for new intervention measures against the development of DE.
Keywords: Diabetic encephalopathy, metabolic reprogramming, Brain insulin resistance, Oxidative Stress, mitophagy, Glycolytic flux, GLP-1 receptor agonists, NAD+ boosters
Received: 08 Sep 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Huai, Chang, Zhu, Ma, Lv, Sun and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Sun, sunjing@njucm.edu.cn
Xiqiao Zhou, zhouxiqiao@njucm.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.