In the news: Vitamin D & Diabetic Neuropathy: AMD Genetic Testing Premature

Vitamin D & Diabetic Neuropathy Symptoms

Vitamin D (25-hydroxyvitamin D) deficiency is common in diabetic patients, and low concentrations are associated with the presence and the severity of various diabetic complications including retinopathy, nephropathy and sensory neuropathy. Vitamin D deficiency has been shown to be an independent risk factor for diabetic peripheral neuropathy (DPN). Two previous studies report that topical and oral vitamin D reduce the symptoms and pain of DPN, leading a research team to prospectively evaluate the effect of vitamin D in DPN.

This randomized, double blind, placebo controlled trial included 112 type 2 diabetic patients with DPN and vitamin D deficiency (1). DPN was assessed using a neuropathy symptom score, a neuropathy disability score, and a nerve conduction study. The primary outcomes were changes in symptoms and disability scores from baseline. Patients received either oral vitamin D capsules (50,000 IU) or placebo once weekly for 8 weeks.

Serum vitamin D levels significantly improved in the vitamin D treatment group compared to the placebo group (p < 0.0001). Similarly, the improvement in neuropathy symptom values was significantly greater in the treatment group than in placebos (p < 0.001). The main symptom improvement observed was in the sensation of neuropathic pain, especially burning and increased sensitivity to stimuli (hyperesthesia). No improvement was seen for the other outcomes.

According to the authors, these findings establish that oral vitamin D corrects vitamin D deficiency, which leads to a reduction in the symptoms of neuropathy. It’s not clear whether the symptom improvements were due to an increase in the pain threshold or to an improvement in the function of the affected nerves, or both. Vitamin D is a potent inducer of neurotrophins and neurotransmitters, and experimentally, it has been shown to increase the action of nerve growth factor – a protein required for developing and maintaining neurons in the peripheral nervous system. While the present trial utilized very large, less frequent doses of vitamin D to correct the deficiency state, such high doses are not necessarily required. In an earlier study in type 2s with neuropathic pain and vitamin D deficiency, a daily mean dose of 2059 IU vitamin D for 3 months significantly reduced pain scores.

Genetic Testing Not Recommended for AMD

Writing in the journal JAMA Ophthalmology, Edwin M. Stone, MD, PhD, an ophthalmologist who specializes in genetic eye diseases at The University of Iowa Carver College of Medicine, presents a reasoned perspective on why genetic testing for AMD is currently unjustified (2).

The author describes the various risks associated with routine genetic testing, and is of the opinion that a comprehensive eye exam with up to date imaging is superior to any current genetic test in predicting the clinical course of AMD. The primary issue with routine genetic testing is that there is no evidence from prospective, randomized clinical trials that genotype testing leads to improved outcomes, according to Dr. Stone.

He points to studies from two different groups (Awh, et al and Chew, et al) that have both used clinical data from AREDS and have come to opposite conclusions. Awh, et al contend that specific ARMS2 and CFH genotypes are associated with different responses to supplemental antioxidants and zinc – a hypothesis based on a retrospective analysis. The author emphasized that the burden of proof of this hypothesis lies with Awh and colleagues. In contrast, Chew et al advise the full complement of AREDS nutrients for AMD patients regardless of genotype, as does Dr. Stone.

The author notes that routine genetic testing for AMD is not recommended by the AAO task force on genetic testing, nor is there consensus on how genetic testing would be integrated into clinical practice. He concludes that routine genetic testing may someday play a role in achieving better outcomes for AREDS patients, but today the risks of such testing outweigh any benefits.

References

1. Shehab D, et al. Prospective evaluation of the effect of short-term oral vitamin D supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract Feb 26, 2015 [Epub ahead of print].
2. Stone EM. Special Communication: Genetic testing for age-related macular degeneration not indicated now. JAMA Ophthalmol. Online March 19, 2015.