Arnold Bloom lecture: Can we reduce the burden of diabetic peripheral neuropathy?
medwireNews: Solomon Tesfaye, Consultant Physician at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield, delivered the Arnold Bloom lecture on diabetic neuropathy. The presentation covered the burden of diabetic peripheral neuropathy (DPN) for patients and healthcare services, the pathophysiological mechanisms of the condition, and how detection and management could be improved in the future.
Tesfaye began by outlining the multifaceted nature of diabetic neuropathy for patients. “Diabetic neuropathy is a number of conditions really, aggregated into one diabetic neuropathy, but actually there are separate conditions and separate etiologies,” he said.
The lecture focused on chronic sensory motor neuropathies affecting the hands and feet.
Highlighting the success of the screening program for diabetic retinopathy in the UK – resulting in retinopathy no longer being the leading cause of blindness among working-age adults – Tesfaye underlined that “everybody now undergoes annual retinopathy screening, and at the earliest changes patients are referred to see an ophthalmologist.”
However, “the same cannot be said for neuropathy; it is the exact opposite,” he said, with 140 patients undergoing amputation every week in the UK as a result of the condition. He noted that diabetic foot ulcer is “worse than some cancers” in terms of 5-year mortality rates according to a 2007 publication, in which rates were reported as approximately 50% for neuropathic ulcer, compared with less than 20% for breast and prostate cancer.
And the estimated annual cost of ulceration and amputation among people with diabetes in the UK is now around £ 1 billion (US$ 1,2 billion; € 1.1 billion), causing “a drain on the NHS,” he stressed.
Furthermore, he explained that painful DPN is often underdiagnosed and undertreated, because “patients do not associate the problems they have in their feet with neuropathy, because we have not educated them.” DPN is often misdiagnosed as arthritis, leading to inappropriate medication, he added.
He said that unlike other chronic painful conditions, “the patient with painful neuropathy in diabetes endures a number of comorbidities”, including nephropathy, unsteadiness and falls, ulcers, and loss of vision.
“We deal with complex patients with huge comorbidities,” he summarized.
However, Tesfaye said that it is a simple matter to improve the early detection of diabetic neuropathy, describing a system implemented in Sheffield that involves a podiatrist checking patients’ feet when they attend retinopathy screening.
“Eye drops have been instilled, patients are sitting doing nothing, and that’s when we attack their feet,” he said. “It’s a fantastic opportunity because everyone attends eye screening.”
“This one-stop shop should be the way forward if you want to tackle diagnosis and amputations; this is what we should be doing, and not increasing the number of foot clinics,” he stressed.
In the next part of his lecture, Tesfaye delved into some of the pathophysiological mechanisms underlying DPN, and addressed why some patients with neuropathy experience severe pain whereas others do not. He outlined data indicating that intra-vascular oxygen saturation and dermal microvascular proliferation are greater among patients with painful DPN than in those without pain.
“Could DPN, hitherto considered a peripheral neuropathy, have a central manifestation?” Tesfaye asked. He then presented evidence suggesting that this could indeed be the case. For example, the N-acetyl-aspartate:choline ratio is “grossly reduced” in patients with DPN, indicating impaired neuron function. Thalamic blood flow was also shown to be increased in patients with painful versus painless neuropathy.
“Could this be a marker of painful neuropathy? Could it be a target for future therapeutic innovation? Could it be a diagnostic marker?” he wondered.
Summarizing the involvement of the central nervous system in DPN, Tesfaye explained that nerve loss leads to atrophy and loss of sensation in the spinal cord and brain, and the loss of small fibers gives rise to central sensitization, which in turn leads to expansion of the receptive field, hyperalgesia, allodynia, and spontaneous pain.
Tesfaye rounded off his lecture by looking at how to manage painful neuropathy. “The only thing we have is risk reduction,” he said, noting that the symptomatic treatments available at present are “not really effective.”
“To improve outcomes for our patients we should really be looking at preventing neuropathy from happening” through proper management of diabetes and lifestyle modification, he added. He also announced a new trial that will be conducted across 12 UK centers to try and address the best way to treat pain among patients with DPN.
The OPTION-DM trial is a head-to-head, double-blind crossover trial that will compare three different treatment pathways using amitriptyline, duloxetine, pregabalin, and combinations of the three drugs to establish the best first-line treatment strategy for these patients, he said.
“Hopefully, in a couple of years’ time, I’ll come and tell you our findings.”
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