Mechanisms, translational opportunities for diabetic polyneuropathy

Diabetic polyneuropathy (DPN) is a common complication of types 1 and 2 diabetes mellitus (DM). Peripheral sensory axons are early and primary targets of DPN, rendering sensory loss, pain and impaired quality of life. While several metabolic and other abnormalities, including abnormal insulin signaling and mitochondrial dysfunction contribute toward DPN, effective therapy to reverse or arrest the disorder is not currently available. DPN is a degenerative condition that involves retraction of distal sensory terminals and failure of regenerative repair. This review summarizes current mechanisms of DPN and potential new approaches that may offer translational opportunities for treatment. Many of these targets have yet to be explored in multiple DM models/paradigms and have not yet entered clinical trials. Nonetheless, specific regeneration pathways may offer a future role to encourage sensory axon resilience and regrowth.