DNA Damage in Diabetes: From Molecular Mechanisms to Clinical Implications
- 1Department of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, Italy
Abstract
A growing body of evidence indicates that diabetes is associated with pronounced DNA damage, ultimately leading to genomic instability. Chronic hyperglycemia induces the production of reactive oxygen and nitrogen species (ROS and RNS), which trigger a cascade of oxidative stress through multiple pathways. These reactive species attack DNA, causing mutations as well as single- and double-strand breaks. Hyperglycemia also promotes the non-enzymatic glycation of DNA causing the formation of advanced glycation end products (AGEs) adducts. Binding of AGEs to the receptors for AGEs (RAGEs) stimulates additional ROS production, thereby amplifying oxidative stress. This state of genomic instability is further promoted by a decline in antioxidant defenses, which allows ROS-induced damage to accumulate, and is sustained by compromised DNA repair mechanisms. Accumulating DNA damage contributes to the development of diabetic micro- and macrovascular complications by triggering destructive mechanisms such as apoptosis, fibrosis, ferroptosis, and pyroptosis that compromise organ function. Additionally, persistent DNA damage elevates the risk of diabetes-associated malignancies and compromises male reproductive health. This review synthesizes current insights into the molecular mechanisms driving hyperglycemia-induced genomic damage and highlights its broad clinical implications. Understanding the multifaceted impact of DNA damage in diabetes provides a comprehensive framework for its role in disease progression and associated comorbidities.
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BibTeX
@article{verni2026damage,
title = {{DNA Damage in Diabetes: From Molecular Mechanisms to Clinical Implications}},
author = {Fiammetta Vernì and Chiara Angioli and Angelo Ferriero and Beatrice Agostini},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219576},
url = {https://www.mdpi.com/1422-0067/27/21/9576},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DNA Damage in Diabetes: From Molecular Mechanisms to Clinical Implications
AU - Fiammetta Vernì
AU - Chiara Angioli
AU - Angelo Ferriero
AU - Beatrice Agostini
PY - 2026
DA - 2026/10/26
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219576
UR - https://www.mdpi.com/1422-0067/27/21/9576
AB - A growing body of evidence indicates that diabetes is associated with pronounced DNA damage, ultimately leading to genomic instability. Chronic hyperglycemia induces the production of reactive oxygen and nitrogen species (ROS and RNS), which trigger a cascade of oxidative stress through multiple pathways. These reactive species attack DNA, causing mutations as well as single- and double-strand breaks. Hyperglycemia also promotes the non-enzymatic glycation of DNA causing the formation of advanced glycation end products (AGEs) adducts. Binding of AGEs to the receptors for AGEs (RAGEs) stimulates additional ROS production, thereby amplifying oxidative stress. This state of genomic instability is further promoted by a decline in antioxidant defenses, which allows ROS-induced damage to accumulate, and is sustained by compromised DNA repair mechanisms. Accumulating DNA damage contributes to the development of diabetic micro- and macrovascular complications by triggering destructive mechanisms such as apoptosis, fibrosis, ferroptosis, and pyroptosis that compromise organ function. Additionally, persistent DNA damage elevates the risk of diabetes-associated malignancies and compromises male reproductive health. This review synthesizes current insights into the molecular mechanisms driving hyperglycemia-induced genomic damage and highlights its broad clinical implications. Understanding the multifaceted impact of DNA damage in diabetes provides a comprehensive framework for its role in disease progression and associated comorbidities.
SN - 1422-0067
ER -