Oxidative Stress and Metabolic Memory in Diabetes: Focus on the Role of Exercise

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Context: Diabetes mellitus and its micro- and macrovascular complications represent a critical global health burden. Epigenetic modifications are recognized as promising biomarkers for predicting the risk of metabolic diseases and as potential therapeutic targets. A healthy lifestyle pattern, such as engaging in physical exercise and adopting appropriate diets, can influence epigenetic markers and diabetes-related complications. Skeletal muscle can retain an exercise memory, whereby its beneficial effects on improving mitochondrial function, reducing oxidative stress, and regulating metabolism persist even after a period of detraining. However, due to the effect of metabolic memory, the persistence of hyperglycemic damage and the occurrence of multiple life-threatening complications may continue to progress in many patients. Evidence Acquisition: Early interventions to reduce mortality rates associated with the disease are of paramount importance. Therefore, understanding the mechanisms of metabolic memory and the role of exercise in it provides comprehensive insights into the mechanisms of pathogenesis and may represent a novel therapeutic target in the diagnosis and management of diabetes. Results: Hyperglycemia resulting from lifestyle factors, stress, underlying diseases, and other causes induces widespread dysfunction in vital central and peripheral organs. The duration of hyperglycemic exposure in different organs significantly influences the response to therapeutic and adjunctive interventions, as metabolic memory becomes established across diverse tissues, thereby complicating treatment. Conclusions: Combination therapy encompassing pharmacotherapy, exercise, dietary modification, and stress management can effectively modulate the multiple destructive pathways induced by hyperglycemia. Exercise contributes to the management of metabolic memory by enhancing muscle memory, yet the timing and type of exercise initiation critically influence preventive and therapeutic outcomes.

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