A growing understanding of trained immunity, a form of long-lasting immune system adaptation, is reshaping how scientists view diabetes and its many complications. A new review highlights how persistent changes in the body’s innate immune system may contribute to the development of diabetes, worsen disease progression, and create new opportunities for treatment.
Diabetes affects hundreds of millions of people worldwide and is a leading cause of cardiovascular disease, kidney disease, vision loss, and other serious health problems. While high blood sugar has long been recognized as a central driver of these complications, increasing attention is now focused on the role of chronic inflammation and immune dysfunction.
The review explains that trained immunity occurs when innate immune cells, such as monocytes and macrophages, undergo lasting changes after exposure to metabolic stress or inflammatory signals. These cells become primed to respond more aggressively to future challenges, creating a sustained inflammatory state that can persist even after the original trigger has disappeared. This phenomenon links metabolic disturbances directly to immune system behavior.
According to the review, factors commonly associated with diabetes—including hyperglycemia, obesity, lipid abnormalities, and changes in the gut microbiome—can activate trained immunity pathways. The resulting inflammatory responses may promote insulin resistance, impair the function of insulin-producing beta cells, and accelerate damage throughout the body.
The effects extend beyond diabetes itself. Evidence summarized in the review suggests that trained immunity may contribute to the progression of atherosclerosis, diabetic kidney disease, delayed wound healing, and potentially other diabetes-related complications. Persistent immune activation appears to influence tissue injury, fibrosis, vascular dysfunction, and chronic inflammation across multiple organs.
The review also identifies several promising therapeutic directions. Potential approaches include targeting inflammatory pathways such as the NLRP3 inflammasome, modifying cellular metabolism, improving gut microbial balance through dietary interventions and microbiome-focused therapies, and exploring vaccination strategies that influence immune programming. These approaches aim not only to control blood glucose levels but also to address the underlying immune mechanisms that drive disease progression.
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Qiming Gong, Yuqing Huang, Fahui Liu, Tingting Zhou, Wei Huang, Yong Xu, Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications, Genes & Diseases, Volume 13, Issue 5, 2026, 101940, https://doi.org/10.1016/j.gendis.2025.101940

Funding
Natural Science Foundation of China 82170834
Natural Science Foundation of China U22A20286
Natural Science Foundation of China 82470854
Sichuan Science and Technology Program (China) 2024YFFK0081
Sichuan Province Cadre Health Research Project (China) ZH2022-1501
Health Commission of Sichuan Province Medical Science and Technology Program (China) 24CXTD02
Clinical Medicine Special Project of Southwest Medical University (Sichuan, China) 2024LCYXZX02
Clinical Medicine Special Project of Southwest Medical University (Sichuan, China) 2024LCYXZX12
Graduate Education and Teaching Program of Southwest Medical University (Sichuan, China) YJG202291
Graduate Education and Teaching Program of Southwest Medical University (Sichuan, China) ZYTS-29