[Recent advances in clinical practice and in basic research on diabetic neuropathy]

With the drastic increase in the number of patients with diabetes, management of neuropathy has become a critical concern because of its intractability and the socio-economic burden it poses. Epidemiological studies have shown that the levels of blood glucose and glycated hemoglobin, the duration of diabetes, and hypertension are important risk factors for the development of neuropathy. Although guidelines for the diagnosis and clinical staging of diabetic neuropathy have been proposed, only nerve conduction studies can provide a reliable diagnosis of the condition. Currently, evaluation of small fiber abnormalities has been given great emphasis, because they often appear early in the course of diabetic neuropathy. Quantitative analysis of epidermal innervation is globally performed for determining the indices of small fiber neuropathy, and recently, laser microscopic evaluation of corneal innervation was proposed as a surrogate technique for skin or nerve biopsy, to serve as a quantitative marker for neuropathy. The advantages of the latter technique are that it is non-invasive and allows for repeated observations. However, the validity of this new method requires further confirmation. Investigations on the pathogenesis of diabetic neuropathy are also increasing and diversifying, and new theories are emerging. The polyol pathway, glycation, and proinflammatory reactions are implicated in peripheral nerve injuries. Further, downstream signaling represented by alterations in protein kinase C, poly (ADP-ribose) polymerase, mitogen-activated protein kinases, and mobilization of transcription factors are likely to result in the neuropathic phenotype. Studies are underway to investigate a novel mechanism of diabetic neuropathy, with a view to developing a highly effective treatment that will restore nerve function and structure.