Emerging Nonpharmacologic Interventions to Treat Diabetic Peripheral Neuropathy.

Significance: Diabetic peripheral neuropathy (DPN), a complication of metabolic syndrome, type I and type II diabetes, leads to sensory changes that include slow nerve conduction, nerve degeneration, loss of sensation, pain, and gate disturbances. These complications remain largely untreatable, although tight glycemic control can prevent neuropathy progression. Nonpharmacologic approaches remain the most impactful to date, but additional advances in treatment approaches are needed. Recent Advances: This review highlights several emerging interventions, including a focus on dietary interventions and physical activity, that continue to show promise for treating DPN. We provide an overview of our current understanding of how exercise can improve aspects of DPN. We also highlight new studies in which a ketogenic diet has been used as an intervention to prevent and reverse DPN. Critical Issues: Both exercise and consuming a ketogenic diet induce systemic and cellular changes that collectively improve complications associated with DPN. Both interventions may involve similar signaling pathways and benefits but also impact DPN through unique mechanisms. Future Directions: These lifestyle interventions are critically important as personalized medicine approaches will likely be needed to identify specific subsets of neuropathy symptoms and deficits in patients, and determine the most impactful treatment. Overall, these two interventions have the potential to provide meaningful relief for patients with DPN and provide new avenues to identify new therapeutic targets.