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Treating Diabetic Neuropathy: Wish List of Therapeutic Improvements
Boston, MA—Neuropathy, which is one of the most common complications of diabetes, is for some individuals the first clue that they have diabetes or prediabetes. Obesity, hyperlipidemia, and hypertension also all play a role in the development and progression of neuropathy.
Eva L. Feldman, MD, PhD, Russell N. DeJong professor of neurology and director, A. Alfred Taubman Medical Institute, University of Michigan, discussed this topic during a symposium at the ADA meeting. She focused on the clinical findings that link prediabetes and the metabolic syndrome with neuropathy.
While researchers look for a better understanding that may point to the mechanisms of diabetic neuropathy, studies have clearly shown that this condition can be halted, and, in some cases, reversed. She said that diet and exercise can be effective at combating diabetic neuropathy, but only for patients who follow the prescribed regimen. Dr Feldman highlighted a study she and colleagues published in Diabetes Care [2006;29(6):1294-1299] that evaluated intraepidermal nerve fiber density (IENFD) in 32 patients with neuropathy associated with impaired glucose tolerance receiving a diet and exercise in- tervention. After 1 year of adherence, patients experienced improvement in distal IENFD and proximal IENFD. The change in proximal IENFD correlated with decreased neuropathic pain (P<.05).
She also addressed if glucose control alone can prevent neuropathy in type 2 diabetes. Data from studies showed glucose control has little effect on diabetic neuropathy in patients with type 2 diabetes. In patients, the metabolic syndrome and not glucose alone underlies the onset and progression of diabetic neuropathy, according to Dr Feldman.
“Diabetic neuropathy is a painful small fiber neuropathy and likely present in 15% of the patients you diagnose with prediabetes,” she said in her summary of the clinical data. “In a preselected group of patients with idiopathic sensory neuropathy, at least one-third of patients have prediabetes and among those, the neuropathy is painful.”
A Real Entity?
J. Robinson Singleton, MD, director, neurophysiology laboratory, Salt Lake City Veterans Administration, and professor of medicine, University of Utah School of Medicine, said there are many unanswered questions about diabetic neuropathy.
For example, is prediabetic neuropathy a real entity? He said that studies by Ziegler et al [Diabetes Care. 2008;31(3):464-469 and Pain Med. 2009;10(2):393-400] found that neuropathy and neuropathic pain is more common in prediabetic patients than controls.
Dr Singleton shared a “wish list” of therapeutic improvements needed to help clinicians treating neuropathy in their patients. These include a more sensitive way to screen patients for prediabetes, effective therapy for chronic neuropathic pain, and treatments to spur sensory axon regeneration and treatments that make distal axons more resilient to metabolic injury.
“We have to recognize treatable neuropathies that occur concomitantly with diabetic neuropathy,” said James W. Russell, MB, ChB, MS, professor of neurology and director, peripheral neuropathy center, University of Maryland, who discussed treatment approaches for diabetic neuropathy. Chronic inflammatory demyelinating polyneuropathy (CIDP) in patients with diabetic neuropathy is an example. One study found that the prevalence of CIDP increased in diabetic patients ≥51 years of age. “This is concerning because it means in patients diagnosed with diabetic polyneuropathy there are clearly going to be subjects who may have CIDP for which there is no appropriate treatment offered.”
Dr Russell also highlighted the role of nutraceuticals in diabetic neuropathy. In many patients with diabetes, there are decreases in vitamin B1, vitamin B12, and vitamin D, he said, citing a study by Foneseca et al [Am J Med. 2013;126(2):141-149]. The double-blind, randomized, placebo-controlled trial in- cluded 214 patients with type 2 diabetes and neuropathy who underwent 24 weeks of treatment with vitamin B in the form of L-methylfolate, methylcobalamin, and pyridoxal-5’-phosphate (LMF-MC-PLP) or placebo. The results showed an improvement in the Neuropathy Total Symptom Score with LMF-MC-PLP versus placebo (P=.013) and the Short Form-36.
“Nutraceuticals may offer benefits either by repleting vitamins that are deficient in diabetes, or by regulating critical metabolic or axonal pathways that may ameliorate the neuropathy. The pathways they affect are more likely to remain self-regulated, resulting in a lower adverse effect profile,” he said.—Eileen Koutnik-Fotopoulos
