UC San Diego

The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multiple organ systems with the blood vessels, eyes, kidneys and nervous systems being particularly vulnerable. These complications of diabetes reduce lifespan, impede quality of life and impose a huge social and economic burden on both the individual and society. Peripheral neuropathy is a debilitating complication that will impact over half of all persons with diabetes. There is no treatment for diabetic neuropathy and a disturbingly long history of therapeutic approaches showing promise in preclinical studies but failing to translate to the clinic. These failures have prompted re-examination of both the animal models and clinical trial design. This review focuses on the functional and structural parameters used as indices of peripheral neuropathy in preclinical and clinical studies and the extent to which they share a common pathogenesis and presentation. Nerve conduction studies in large myelinated fibers have long been the mainstay of preclinical efficacy screening programs and clinical trials, supplemented by quantitative sensory tests. However, a more refined approach is emerging that incorporates measures of small fiber density in the skin and cornea alongside these traditional assays at both preclinical and clinical phases.