Low Vitamin D Levels Common in Painful Diabetic Neuropathy

Miriam E Tucker

June 07, 2015

BOSTON — Painful diabetic peripheral neuropathy is associated with significantly reduced vitamin D levels, independent of sunlight exposure, a new study finds.

The study, presented here at the American Diabetes Association (ADA) 2015 Scientific Sessions, suggests a possible role of vitamin D in the pathogenesis of painful diabetic peripheral neuropathy and therefore a potential role of supplementation in its treatment, pending the results of randomized clinical trials, study author Dinesh Selvarajah, MD, of the University of Sheffield, United Kingdom, told Medscape Medical News.

Previous studies demonstrating a link between low vitamin D and neuropathy have not accounted for seasonal differences in vitamin D nor for activity variations that affect vitamin D exposure. This is the first study to carefully control for those factors, Dr Selvarajah noted.

"We've certainly got a smoking gun. We've got a proof of concept. Now we need to do an intervention study to show whether this is a significant finding, because if it is, it's a simple enough treatment," he said.

Asked to comment, James W Russell, MBChB, professor of neurology, anatomy, and neurobiology at the University of Maryland, Baltimore, said he is fairly confident this is a real issue.

"There are now convincing data that low vitamin D levels predispose to developing type 2 diabetes.…Even though we may not have the definitive evidence for diabetic neuropathy or prediabetic neuropathy, it's highly likely that it's predisposing you to developing diabetes, and there's an association with worsening diabetes early in the disease, and it probably is affecting neuropathy as well," he said.

Dr Russell said he checks vitamin D levels in all his patients with diabetic peripheral neuropathy and that over 90% have low levels, so he gives them all supplements.

"Our approach is that we look at factors that may be increasing the risk for…worsening complications. If you can make a 5% difference by doing this, that could be very important. But there's no really hard science yet. This [current paper] is the beginning of the evidence."

Session moderator Rayaz A Malik, MBChB, FRCP, PhD, professor of medicine and consultant physician at Weill Cornell Medical School, Qatar, and Central Manchester University Teaching Hospitals, United Kingdom, noted that two open-label studies of large doses of vitamin D found substantial reductions in pain scores. But, he noted, "You need a randomized study."

Independent Association of Painful Neuropathy and Low Vitamin D

Dr Selvarajah and colleagues studied 45 patients with type 2 diabetes — 17 with painful neuropathy, 14 with painless neuropathy, and 14 with no neuropathy — along with 14 healthy volunteers. All had vitamin D levels measured between May and September and answered questionnaires to assess sunlight exposure and neuropathy symptoms (Douleur Neuropathique 4 [DN4]).


They also underwent detailed clinical, neurophysiological, and lower-limb skin intra-epidermal nerve-fiber density (IENFD) assessments. They were divided into three groups based on the Neuropathy Impairment Score of the Lower Limb (NIS-LL) and the DN4.

The painful-neuropathy patients had a mean age of 62 years, compared with 63 for the painless neuropathy, 55 for no neuropathy, and 52 for the healthy volunteers (P = .01). They also had a significantly higher body mass index (BMI), 33 kg/m2, vs 31 kg/m2, 30 kg/m2 , and 26 kg/m2, respectively (P = .02).

After adjustment for age, BMI, and sunlight exposure, vitamin D levels were significantly lower in the painful-neuropathy group, at 34.34 nmol/L vs 53.22 for painless neuropathy, 50.00 for no neuropathy, and 64.95 for the healthy volunteers (P = .01).


Main group differences were significant between painful and painless neuropathy (P = .02) and painful neuropathy vs healthy controls (P = .002), and there was a significant positive correlation between vitamin D levels and sunlight exposure (P = .003).

Sunlight exposure and activity scores showed no significant difference among the four groups (P = .46). Vitamin D and subepidermal nerve-fiber density were also significantly correlated in the neuropathy group (P = .008).

Nothing to Lose From Vitamin D Supplementation?

Dr Russell told Medscape Medical News that while randomized data aren't yet available, there's no harm in supplementing now and there could be benefit.


"Little things like this make a big difference in the long term. If you supplement with vitamin D for 10 years — we don't have these data, but it's very likely — if you compared the person who was supplemented vs the one who wasn't, you'd find a significant difference."

Dr Malik noted that a large randomized clinical trial of vitamin D would probably have to be funded by the government or other interested party rather than the pharmaceutical industry. "The key problem is, nobody is going to make money from vitamin D [research and development], so nobody's pushing it. It's extremely cheap."

Dr Selvarajah and Dr Malik have no relevant financial relationships. Dr Russell has received funds from Impeto Medical, the National Institutes of Health and the Veterans Affairs Administration.


American Diabetes Association 2015 Scientific Sessions; June 6, 2015: Boston, Massachusetts. Abstract 627-P

Source: http://www.medscape.com/viewarticle/846044