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Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide, with a rapidly increasing incidence driven by urbanization and lifestyle changes. It is characterized by chronic hyperglycemia resulting from insulin resistance and progressive β-cell dysfunction, leading to systemic disturbances in carbohydrate, lipid, and protein metabolism.Emerging evidence identifies mitochondrial in the pathogenesis of T2DM, where impaired oxidative phosphorylation, altered mitochondrial dynamics (fusion–fission imbalance), and defective mitophagy contribute to reduced ATP production and β-cell failure. Hyperglycemia-induced overproduction of reactive oxygen species (ROS) exacerbates oxidative stress, disrupts redox homeostasis, and activates inflammatory and apoptotic pathways, thereby reinforcing insulin resistance and cellular injury. Mitochondrial impairment also plays a pivotal role in the development of diabetic complications, including vasculopathy and neuropathy, through endothelial dysfunction, AGE–RAGE signaling, chronic inflammation, and defective insulin signaling pathways such as PI3K/Akt. Understanding the intricate interplay between mitochondrial dysfunction, oxidative stress, and metabolic inflammation may provide novel therapeutic targets for preventing disease progression and its long-term microvascular and macrovascular complications. This review offers a novel, integrative synthesis of the latest advancements in mitochondrial molecular dynamics—ranging from mitophagy impairment and mtDNA damage to retrograde signaling—to delineate their causative role in the exacerbation of diabetic symptoms. By bridging the gap between basic pathophysiology and clinical intervention, this work establishes a refined conceptual framework that identifies specific mitochondrial molecular checkpoints as potential therapeutic targets. Consequently, this perspective moves beyond a descriptive summary to provide a strategic, evidence-based roadmap for developing precision-medicine interventions aimed at mitigating metabolic dysfunction and improving clinical outcomes in patients with diabetes.

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