Lumos for the long trail: Strategies for clinical diagnosis and severity staging for diabetic polyneuropathy and future directions.

Diabetic polyneuropathy, which is a chronic symmetrical length-dependent sensorimotor polyneuropathy, is the most common form of diabetic neuropathy. Although diabetic polyneuropathy is the most important risk factor in cases of diabetic foot, given its poor prognosis, the criteria for diagnosis and staging of diabetic polyneuropathy has not been established; consequently, no disease-modifying treatment is available. Most criteria and scoring systems that were previously proposed consist of clinical signs, symptoms and quantitative examinations, including sensory function tests and nerve conduction study. However, in diabetic polyneuropathy, clinical symptoms, including numbness, pain and allodynia, show no significant correlation with the development of pathophysiological changes in the peripheral nervous system. Therefore, these proposed criteria and scoring systems have failed to become a universal clinical end-point for large-scale clinical trials evaluating the prognosis in diabetes patients. We should use quantitative examinations of which validity has been proven. Nerve conduction study, for example, has been proven effective to evaluate dysfunctions of large nerve fibers. Baba's classification, which uses a nerve conduction study, is one of the most promising diagnostic methods. Loss of small nerve fibers can be determined using corneal confocal microscopy and intra-epidermal nerve fiber density. However, no staging criteria have been proposed using these quantitative evaluations for small fiber neuropathy. To establish a novel diagnostic and staging criteria of diabetic polyneuropathy, we propose three principles to be considered: (i) include only generalizable objective quantitative tests; (ii) exclude clinical symptoms and signs; and (iii) do not restrictively exclude other causes of polyneuropathy.