Diabetic Peripheral Neuropathic Pain

Treating Diabetic Neuropathy

Eileen Koutnik-Fotopoulos, Contributor

Neuropathy, which is one of the most common complications of diabetes, is the first symptom for some patients 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 at A. Alfred Taubman Medical Institute at the University of Michigan, focused on the clinical findings that link prediabetes and the metabolic syndrome with neuropathy at the American Diabetes Association’s 75th Scientific Sessions.

While researchers search 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. Feldman said that diet and exercise can be effective at combating diabetic neuropathy, but only for patients who follow the prescribed regimen. In one of her own studies,1 Feldman and colleagues evaluated intraepidermal nerve fiber density (IENFD) in 32 patients with neuropathy associated with impaired glucose tolerance receiving a diet and exercise intervention. After 1 year of being adherent, patients experienced improvement in distal IENFD and proximal IENFD. The change in proximal IENFD correlated with decreased neuropathic pain (P<.05).

On the topic of whether glucose control alone can prevent neuropathy in type 2 diabetes, data showed that glucose control has little effect on diabetic neuropathy in patients with type 2 diabetes. In patients with type 2 diabetes, the metabolic syndrome and not glucose alone underlies the onset and progression of diabetic neuropathy.

“Diabetic neuropathy is a painful small fiber neuropathy and likely present in 15% of the patients you diagnose with prediabetes,” Feldman 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.”

J. Robinson Singleton, MD, director of the neurophysiology laboratory at the Salt Lake City Veterans Administration and professor of medicine at the University of Utah School of Medicine, said there many unanswered questions about diabetic neuropathy.

For example, is prediabetic neuropathy a real entity? Research by Ziegler et al2,3 found that neuropathy and neuropathic pain is more common in prediabetic patients than controls. 

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 really have to recognize treatable neuropathies that occur concomitantly with diabetic neuropathy,” said James W. Russell, MB, ChB, MS, professor of neurology and director of the peripheral neuropathy center at the University School of Medicine, 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 and older. “This is concerning because it means in patients diagnosed with diabetic polyneuropathy there are clearly going to be subjects who may have CIDP and where there may not be appropriate treatment offered.”

Russell also highlighted the role of nutraceuticals in diabetic neuropathy. In many patients with diabetes, there are decreases in vitamins B1, B12, and D, he said, citing a study by Foneseca et al4. The double-blind, randomized, placebo-controlled trial included 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.


1.Singleton JR, Smith G, Bromberg M. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care. 2006;29(6):1294-1299.

2.Ziegler D, Rathmann W, Dickhaus T, et al. Prevalence of polyneuropathy in pre-daibetes and diabetes is associated with abdominal obesity and microangiopathy. Diabetes Care. 2008;31(3):464-469. 

3.Ziegler D, Rathmann W, Dickhaus T, et al. Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Med. 2009;10(2):393-400.

4.Fonseca V, Lavery L, Thethi T, et al. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med. 2013;126(2):