Recent advances in the management of diabetic distal symmetrical polyneuropathy.

There is now little doubt that poor blood glucose control is an important risk factor for the development of diabetic peripheral neuropathy (DPN). Furthermore, traditional cardiovascular risk factors for macrovascular disease appear to be associated with an increased risk of DPN. The recently established International Expert Group on Diabetic Neuropathy has recommended new criteria for the diagnosis of DPN in the context of clinical and research settings. Studies in experimental diabetes examining the pathogenesis of DPN have identified a number of metabolic abnormalities including polyol pathway hyperactivity, increased advanced glycation end-point formation, alterations in the protein kinase C beta pathway through diacylglycerol and oxidative stress. There is now strong evidence implicating nerve ischemia as the cause of DPN. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. These endoneurial microvascular changes strongly correlate with clinical severity and the degree of nerve-fiber pathology. Unfortunately, many compounds that have been effective in animal models of neuropathy have not been successful in human diabetic neuropathy. The only compounds found to be efficacious in human diabetic neuropathy, and are in clinical use, are the anti-oxidant, α-lipoic acid and the aldose reductase inhibitor, epalrestat. Overall, the evidence emphasizes the importance of vascular dysfunction, driven by metabolic change, in the etiology of DPN, and highlights potential therapeutic approaches. Epidemiological data on diabetic painful neuropathic pain (DPNP) are limited. In one population-based study, the prevalence of DPNP, as assessed by a structured questionnaire and examination, was estimated at 16%. It was notable that, of these patients, 12.5% had never reported symptoms to their doctor and 39% had never received treatment for their pain. Thus, despite being common, DPNP continues to be underdiagnosed and undertreated. Pharmacological treatment of DPNP include tricyclic compounds, serotonin noradrenalin reuptake inhibitors, the anti-oxidant α-lipoic acid, anticonvulsants, opiates, membrane stabilizers, topical capsaicin and so on. Management of the patient with DPNP must be tailored to individual requirements and will depend on the presence of other comorbidities. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00083.x).