Exercise-induced metabolic remodeling in type 2 diabetes mellitus: insights from metabolomics.

Type 2 diabetes mellitus (T2DM) is one of the most pressing global public health challenges. Exercise intervention, as a cost-effective and safe non-pharmacological strategy, exerts its metabolic benefits through coordinated multi-organ and multi-target regulation. Metabolomics technologies provide powerful tools for dissecting the molecular mechanisms underlying exercise intervention in T2DM. This narrative review summarizes current evidence on metabolic dysregulation in T2DM and the metabolic mechanisms underlying exercise intervention, with particular emphasis on insights provided by metabolomics. Furthermore, it elaborates the mechanisms by which exercise intervention systemically reverses T2DM-associated metabolic abnormalities: restoring tricarboxylic acid cycle flux to alleviate glycolytic stress; accelerating branched-chain amino acid oxidative catabolism to rectify aromatic amino acid metabolic disturbances; and promoting fatty acid oxidation while clearing lipotoxic products. In addition, this review highlights the clinical potential of metabolomics for predicting exercise responsiveness, dynamically evaluating intervention outcomes and safety, thereby providing a potential basis for more individualized exercise intervention strategies in T2DM.