Prehabilitation in patients with diabetes: targeting metabolic dysfunction to improve perioperative outcomes

Patients with diabetes mellitus experience disproportionately worse postoperative outcomes, reflecting an underlying metabolic dysfunction that conventional perioperative optimization strategies fail to address. Although prehabilitation improves outcomes in selected surgical populations, its effectiveness in diabetes remains inconsistent, suggesting a mismatch between intervention strategies and the mechanisms driving perioperative risk. This review aimed to evaluate the role of metabolic dysfunction in perioperative risk among patients with diabetes and to propose a mechanism-informed prehabilitation framework targeting key metabolic disturbances. Evidence from clinical studies, systematic reviews, and perioperative guidelines was synthesized to develop a structured framework linking metabolic targets with targeted interventions within perioperative care pathways. Key metabolic disturbances, including insulin resistance, impaired metabolic flexibility, mitochondrial dysfunction, inflammation, and glycemic variability, amplify the surgical stress response and impair recovery in these patients. Conventional multimodal prehabilitation fails to adequately address these mechanisms. A targeted metabolic optimization approach incorporating exercise-based conditioning, nutritional optimization, glycemic management (including continuous glucose monitoring), and pharmacological modulation enables targeted interventions across these domains. Individualization strategies based on dominant metabolic features improves clinical applicability. The integration of this approach within perioperative pathways, including enhanced recovery after surgery (ERAS), provides a structured strategy to improve metabolic stability and perioperative resilience. Prehabilitation in patients with diabetes should shift from generalized multimodal strategies to targeted strategies involving metabolic optimization aligned with the underlying pathophysiology. A personalized and mechanism-informed approach integrated within the ERAS pathways may improve perioperative outcomes in this high-risk population. Prospective studies are needed to validate this strategy.