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On-line Diabetes Resources

Part 15: Diabetic Neuropathy

By David Mendosa

Last Update: September 21, 2008

This Web page brings together in one place descriptions of and links to only those Web pages dealing with diabetic neuropathy, but is linked to the 15 other On-line Diabetes Resources pages dealing with other Web pages, other parts of the Internet, and other on-line services.

  1. The Peripheral Neuropathy (Sensorimotor Polyneuropathy) web page at http://www.healthopedia.com/peripheral-neuropathy/ provides excellent background information.

  2. B. Eliot Cole, MD, the executive director of the American Society of Pain Educators, writes in the foreword to the consensus guidelines: assessment, diagnosis, and treatment of diabetic peripheral neuropathic pain at http://www.mayoclinicproceedings.com/pdf/DPNPSuppl.pdf that: Four medications were thought to be first-tier therapies for diabetic peripheral neuropathic pain: duloxetine, oxycodone (controlled release), pregabalin, and the tricyclic antidepressants as a class. Second-tier agents included the anticonvulsants carbamazepine, gabapentin, and lamotrigine; the mixed “antidepressant-opioid” tramadol; and the antidepressant venlafaxine (extended release). The topical agents capsaicin and lidocaine; antidepressants bupropion, citalopram, and paroxetine; anticonvulsants phenytoin and topiramate; and opioid methadone were honorable mentions.

  3. Circulator Boot Corporation in Malvern, Pennsylvania, offers the Circulator Boot, a non-invasive treatment approved by the FDA for peripheral arterial insufficiency, rest pain, ischemic ulcers, claudication, and congestive heart failure. You can call (610) 240-9980 for additional information and a Circulator Boot center near you. The URL is
    http://www.circulatorboot.com/.

  4. Diabetica Solutions Inc. (formerly Xilas Medical) in San Antonio, Texas provides an FDA-approved device that makes it easy to check the skin temperature on the bottom of our feet every day. If one foot is 4 degrees warmer than the other, it is an early warning sign that an ulcer is developing. With that knowledge we can take action to prevent ulcers and therefore prevent amputations. The URL is
    http://www.temptouch.com

  5. A common nutrient sold as a dietary supplement called acetyl-L-carnitine seems to help ease the pain caused by diabetic neuropathy, according to researchers. Note that two of the four researchers include representatives from Signa-Tau Research, which manufactures the stuff. The lead researcher is an MD/PhD from the department of pathology and neurology at Wayne State University, Detroit.

    They evaluated data from two randomized placebo-controlled trials carried out over a year on more than 1,200 diabetic patients in the US, Canada, and Europe. The studies included tests on both 500mg and 1,000 mg doses of acetyl-L-carnitine daily.

    Writing "Acetyl-L-Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy" in the January issue (pages 89 to 94) of Diabetes Care, the researchers report that pain was significantly improved in one study and in the combined cohort taking the 1,000 mg dose.

    Pain relief was greatest among those who had diabetes for the shortest time period, they noted. These patients also showed improvements in nerve structure and perception of vibration.

  6. The Food and Drug Administration has approved Pfizer's Lyrica pill to treat nerve pain associated with diabetic neuropathy (and shingles). It is the successor to Pfizer's Neurontin, now also available as a generic. Pfizer hasn't set a date for Lyrica's introduction in the United States or a price. Lyrica will compete with Lilly's Cymbalta, which the F.D.A. cleared in September as a treatment for the pain of peripheral neuropathy. This information comes from http://www.nytimes.com/2005/01/01/business/01pfizer.html?oref=login

  7. The "Diabetic Foot Information and Resources," is maintained by Craig Payne, a lecturer in the Department of Podiatry at La Trobe University, Melbourne, Australia. The lecture notes on diabetes for students are at La Trobe University are available on his website. The URL is
    http://www.diabetic-foot.com.au/

  8. An experimental drug seems to combat the underlying cause of diabetic neuropathy. High levels of sorbitol in nerves is associated with nerve damage, at least in animals. An aldose reductase called AS-3201 reduces average nerve sorbitol concentrations from 65 percent to 84 percent, depending on the dose. The article is in the October 2004 issue of Diabetes Care and the abstract is online at http://care.diabetesjournals.org/cgi/content/abstract/27/10/2369

  9. Lilly's duloxetine (Cymbalta) is the first medication approved by FDA for treatment of neuropathic pain associated with diabetes. Duloxetine has a dual mechanism of action. It targets both serotonin and norepinephrine reuptake. One other selective serotonin and norepinephrine reuptake inhibitor (SSNRI) is currently on the American market, venlafaxine (Effexor). Duloxetine is contraindicated in patients taking MAO inhibitors and in patients with hepatic insufficiency, end-stage renal disease, or uncontrolled narrow-angle glaucoma. See http://www.medicalnewstoday.com/medicalnews.php?newsid=13374

  10. Patients with painful diabetic polyneuropathy experience significantly improve pain and quality-of-life ratings when treated with up to four 5% lidocaine patches for up to 18 hours per day. The treatment is well tolerated. As reported in the Archives of Neurology, Dr. Richard L. Barbano from the University of Rochester in New York and colleagues tested the patch on 56 patients. Since it was an the open-label design, a randomized controlled trial is necessary to confirm the results. See The 5% lidocaine patch in diabetic polyneuropathy

  11. The Quigley Corp. in Doylestown, Pennsylvania, has completed a Phase 2 trial of QR-333 for the symptoms of peripheral diabetic neuropathy. The study concluded that subjects taking QR-333 had 67 percent of their symptoms improve. See http://quigleyco.com/news/nr/030304.php.

  12. Ruboxistaurin (LY333531) is an oral protein kinase C (PKC) beta-inhibitor that Eli Lilly and Co. currently has in phase III clinical trials for diabetic peripheral neuropathy. The neuropathy study should be done in 2004. Protein kinase C activation has been implicated in the underlying process leading to diabetic microvascular complications including diabetic peripheral neuropathy. Phase II results presented in abstract form suggest that ruboxistaurin may improve neurological reflexes in the leg and total symptom scores. Further trials are required to confirm any long-term reduction in neuropathic ulceration or other complications. Ruboxistaurin is also in phase III trials for diabetic retinopathy. See http://pcpoh.bham.ac.uk/publichealth/horizon/PDF_files/2003reports/Ruboxistaurin.pdf

  13. The Stockton Group in Birmingham, Alabama, offers the Therapeutic Foot Care System to correct dry, rough, cracked feet—usually within a week. The system includes a pair of washable slippers and a four-ounce jar of deep moisturizing foot cream. The foot cream includes Vitamin A, Vitamin E, mink oil, fennel hops, lanolin, aloe vera, mistletoe, balm mist, matricara, octydodeconal, sodium ceterayl sulfate, castor oil, cetealyurea, petrolatum, propylene glycol, yarrow, and allant. The toll-free phone number is (800) 261-6004 and the URL is
    http://www.foottreatment.com

  14. Numerous clinical trials have demonstrated that Benfotiamine is effective at reducing the pain of diabetic neuropathy, and no side effects or signs of toxicity have emerged. Based on these trials, Benfotiamine has been approved for use as a therapy for neuropathy in Germany for more than a decade. Furthermore, Benfotiamine is not just an pain killer, but actually improves nerve functioning. Free online abstracts of Benfotiamine studies include "Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy", "Therapeutic efficacy of 'Milgamma' in patients with painful diabetic neuropathy," and "A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy."

  15. "Painful Diabetic Peripheral Neuropathy Relieved With Use of Oral Topiramate" in the title of a study in the Southern Medical Journal that Medscape.com has online at http://www.medscape.com/viewarticle/457550?mpid=16085. Topiramate is sold under the brand name Topamax.

  16. Silicon "Dynamic" Orthotics use silicon fluid to cushion shock from your foot to your lower back. "I have been wearing these for about 10 years now," a correspondent tells me. "I use them as a perhaps unorthodox treatment for neuropathic pain of the feet. I couldn't get along with out them. I, of course, have no financial connection with this doctor or his web site—I'm just an appreciative user." The doctor is Dennis Kiper, a California-based podiatrist, and the Web site is
    http://www.drkiper.com

  17. A collaborative study between Mayo Clinic in Rochester, Minnesota, and a Russian medical center in Moscow has found that alpha lipoic acid significantly and rapidly reduces the frequency and severity of symptoms of diabetic neuropathy. The study included 120 people with type 1 or 2 diabetes and the symptoms of diabetic sensorimotor polyneuropathy.The patients were randomized to receive either a daily dose of 600 mg alpha lipoic acid intravenously or a placebo, following one week in which all participants received placebo. The study was double-blinded so neither patients nor investigators knew which patients received each substance.

    Those who took alpha lipoic acid saw a 5.7-point total symptom score improvement from the start of the trial, while those who took a placebo only improved 1.8 points. There were no unfavorable side effects to the alpha lipoic acid.

    However, the Food and Drug Administration has not yet approved the drug for this purpose. The March 2003 issue of Diabetes Care reported the study in "The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid ".

  18. A drug used primarily to prevent and treat angina and to treat acute heart attacks and heart failure may also provide temporary relief from the pain of diabetic neuropathy. A study in the October 2002 issue of Diabetes Care, found that isosorbide dinitrate (ISDN), generates nitric oxide and relieves pain and burning. Impaired nitric oxide generation is implicated in diabetic neuropathy. "Treatment of Chronic Painful Diabetic Neuropathy With Isosorbide Dinitrate Spray: A double-blind placebo-controlled cross-over study" by Kevin C.J. Yuen et al. is online at http://care.diabetesjournals.org/cgi/content/full/25/10/1699.

    Nutrients for Neuropathy

  19. Nutrients for Neuropathy is the third volume in John Senneff’s "Numb Toes Series." Nutrients for Neuropathy doesn’t quite have the catchy title of its predecessors, Numb Toes and Aching Soles and Numb Toes and Other Woes, yet the more limited scope of the current book allows John to go into even greater depth.

    These books come from the patient standpoint. John, a retired attorney, suffers from peripheral neuropathy. But don’t be concerned about legaleze here. John writes with extraordinary clarity in this 172-page paperback book. This is an easy read on a hard subject. Just published by http://www.medpress.com, Nutrients for Neuropathy lists for $19.95.

  20. The Official Patient's Sourcebook on DIABETIC NEUROPATHY is a new book from Icon Health Publications. I review it at http://www.mendosa.com/diabetes_update_48.htm. The company's URL is
    http://www.icongrouponline.com/health/Diabetic_Neuropathy.html

  21. Patients with painful diabetic neuropathy might have defective local vasodilatory dynamics contributing to nerve damage and symptoms. In a short-term study reported in the October 2002 issue of Diabetes Care, it was found that topical application of a nitric oxide donor, isosorbide dinitrate, reduced overall neuropathic pain and burning sensation. The abstract is on-line at http://care.diabetesjournals.org/cgi/content/abstract/25/10/1699

  22. Curis Inc. in Cambridge, Massachusetts, works to identify and stimulate key pathways of repair and regeneration, focusing specifically on the Hedgehog pathway, which is essential for the formation of normal nerves in the peripheral nervous system as well as in the central nervous system. "Using rodent models of diabetic neuropathy (in which the animal loses peripheral sensory and motor ability), scientists in the United Kingdom have shown that SHh [Sonic Hedgehog protein] restores normal nerve function as measured by nerve conduction velocity," according to the company's annual report for the 2001 fiscal year. "This demonstrated improvement in function was dose-dependent and improved both sensory and motor ability. To our knowledge, this is the first time that there has been complete restoration of both motor and sensory nerve function in an animal model of diabetic neuropathy."

    The annual report refers to findings presented by Dr. David Tomlinson of the University of Manchester in November 2000 presented findings at the Fifth Annual Diabetic Neuropathy Satellite Meeting of the Society for Diabetic Neuropathy. They showed that treatment with the Sonic Hedgehog protein restored nerve function to normal in pre-clinical models of diabetic neuropathy. See http://www.focusonals.com/news81.htm.

    See also "Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists" by Maria Frank-Kamenetsky et al, Journal of Biology, 2002, I:10, online at http://jbiol.com/press/porter.pdf

    The company's URL is
    http://www.curis.com

  23. The Anodyne Therapy System at least temporarily reverses the symptoms of peripheral neuropathy in people with diabetes. Developed by Anodyne Therapeutics LLC in Aurora, Colorado, the company is now part of MedAssist Group in Tampa, Florida. Thomas Burke, one of the authors and a former associate professor at the CU Health Sciences Center, was the president of Integrated Systems Physiology and is now the MedAssist director of research and clinical affairs. Dr. Burke has authorized me to put up a link here to a remarkable journal article that he and two colleagues just published. The article, "Symptomatic Reversal of Peripheral Neuropathy in Patients with Diabetes" by Alan B. Kochman, Dale H. Carnegie, and Thomas J. Burke appeared in the March 2002 issue of the Journal of the American Podiatric Medical Association, pp. 125-130. You can download the article at http://www.mendosa.com/MIRE.pdf.

    The article says that 98% of the 48 subjects had improved sensation after six treatments, and all subjects had improved sensation after 12 treatments. "This is the first highly successful, noninvasive, drug-free theraphy that restores, at least temporarily, neural sensation in subjects with diabetes," the article states.

    "We have done another 40 patients, 10 each at four different sites," Dr. Burke tells me. "Results are, frankly, amazing—97% success rate after 10-12 treatments. Often feeling begins to be restored after just one treatment."

    The gold standard of clinical studies is a double-blind, randomized, placebo-controlled study in a peer-reviewed journal. That's what "Restoration of Sensation, Reduced Pain, and Improved Balance in Subjects With Diabetic Peripheral Neuropathy" in the January 2004 issue of Diabetes Care, an official organ of the American Diabetes Association, showed. The study concluded that Anodyne Therapy "treatments improve sensation in the feet of subjects with DPN [diabetic peripheral neuropathy], improve balance, and reduce pain." The full article is online at http://care.diabetesjournals.org/cgi/content/full/27/1/168.

    The company's website is Anodyne Therapy.

  24. The Institute for Diabetes Discovery in Branford, Connecticut, is a biotech startup focusing on the discovery of new treatments and therapeutics for diabetes. Its leading candidate is called Lidorestat (formerly IDD 676), which is an aldose reductase inhibitor (ARI). This class of drugs treats peripheral diabetic neuropathy. In October 1999 the company filed an Investigational New Drug Application (IND) with the Food and Drug Administration. The company is currently enrolling patients for Phase 2 trials in the U.S. and Canada to identify efficacy and safety of dosage, a spokesperson tells me. The URL is
    http://www.idd-diabetes.com/

  25. Progressive Research Labs Inc. in Austin, Texas, now offers Neuropathy Nutrition Rx to support healthy nerves and circulation. Its contents include gamma linoleic acid (the essential fatty acid in evening primrose oil and borage oil) and alpha lipoic acid. The toll-free phone is (800) 877-0966 and the URL is
    http://www.prlab.com/neuropathy_nutrition.htm

    Numb Toes and Other Woes

  26. Here is the sequel to John A. Senneff's Numb Toes and Aching Soles: Coping with Peripheral Neuropathy, published two years ago. The same author has now updated that indespensible resource for anyone who suffers from peripheral neuropathy with new information on pain medications, medical theraphies, supplements, alternative and complementary strategies, and experimental therapies that are just emerging from the laboratories. Published in June 2001, this 250 page soft cover book lists for $22.95 and is available from
    http://www.medpress.com/

    Numb Toes and Aching Soles

  27. Here finally is a comprehensive guide to help the millions of people with peripheral neuropathy, half of whom have it as a consequence of diabetes. Numb Toes and Aching Soles: Coping with Peripheral Neuropathy is by John A. Senneff, a retired attorney who himself has peripheral neuropathy. It covers everything— causes, symptoms, testing, and treatments, including more than 200 patient comments on which of these treatments work for them and which ones don't. The treatments considered are everything from the most traditional to the furthest alternatives. Published in 1999, this 300 page soft cover book lists for $19.95 and is available from
    http://www.medpress.com/

  28. A. Lee Dellon, M.D., a plastic surgeon practicing in Baltimore, offers surgery for diabetic neuropathy. The procedure is quite controversial. His Web site is
    http://www.dellon.com/

  29. "Neuropathy (Nerve Damage) - An Update" is a detailed article. The URL is
    http://www.joslin.harvard.edu/education/library/neuropathy.html

  30. The Diabetic Neuropathy Support Group is for anyone who is afflicted with this complication and needs support. The founder and moderator is J.C. Giguere and he can be reached at neuropathy@shaw.ca, and the URL is
    http://health.groups.yahoo.com/group/diabeticneuropathy/

  31. AlternativeDiabetes.com provides remarkably even-handed information about a wide variety of non-traditional therapies for diabetes and its complications. It includes several pages of excellent information about neuropathy. The URL is
    http://www.alternativediabetes.com/

  32. "Memantine Significantly Reduces Peripheral Neuropathy Pain In Diabetics" is a Neurobiological Technologies Inc. press release about the company's promising drug, which is in Phase II clinical trials. The The company's Web site address is
    http://www.ntii.com

  33. Diabetic Neuropathy: The Nerve Damage of Diabetes is exactly the same as the National Institutes of Health printed publication No. 95-3185 of July 1995. The URL is
    http://www.niddk.nih.gov/health/diabetes/pubs/neuro/neuro.htm

  34. The Neuropathy Association headquarted in New York City is a public, nonprofit organization established by people with neuropathy and their families or friends to help those who suffer from disorders that affect the peripheral nerves. It toll-free phone number is (800) 247-6968 and the URL is
    http://www.neuropathy.org/

  35. The Neuropathy Trust is a voluntary non-profit organization in the U.K. established to provide emotional support to people with peripheral neuropathy. The URL is
    http://www.neuropathy-trust.org/

  36. Excite.Health/WebMD have a detailed article about neuropathy on their joint site. The URL is
    http://health.excite.com/content/dmk/dmk_article_56143

  37. "Diabetic Neuropathy: What You Can Do About It" is a basic primer from the American Academy of Family Physicians. The URL is
    http://familydoctor.org/handouts/050.html

  38. "Lipoic acid in the stimulation of glucose uptake and the treatment of diabetes and diabetic neuropathy" is chapter 2 of an extensive on-line publication about alpha lipoic acid. The author is Edward A. Byrd, who founded Medical Research Institute in Aptos, California. MRI is a research and development organization for the manufacture, promotion, and marketing of lipoic acid. Please note that although MRI is headquartered in the same little California town where I live and work, I have no connection to the company other than reading its pages on the Web. The URL is
    http://www.lipoic.com/chapter2.html

  39. "Effects of 3-week oral treatment with the antioxidant thioctic acid (-lipoic acid) in symptomatic diabetic polyneuropathy" indicated "that oral treatment with 600mg of TA [thioctic acid, aka alpha lipoic acid] t.i.d. [three times a day] for 3 weeks may improve symptoms and deficits resulting from polyneuropathy in Type 2 diabetic patients, without causing significant adverse reactions." The abstract of this study in the December 1999 issue of Diabetic Medicine is online at
    Effects of thioctic acid

  40. A Multidisciplinary Approach to Diabetic Neuropathy Treatment suggests a combination of prescription drugs and a large number of ancillary nutrients for treating this major diabetic complication. The URL is
    http://www.geocities.com/bsy53/dn/neuropat.html

  41. "Neuropathy" is the American Diabetes Association's introduction to this complication of diabetes. The URL is
    http://www.diabetes.org/main/type1/complications/neuropathy/neuropathy.jsp

  42. "Standardized Measures in Diabetic Neuropathy" is the American Diabetes Association's consensus statement for its Clinical Practice Recommendations. The URL is
    http://www.diabetes.org/DiabetesCare/Supplement/s72.htm

  43. "Nerves" is a section of Chapter 12 "Complications" of the Healing Handbook for Persons with Diabetes. The URL is
    http://www.umassmed.edu/diabeteshandbook/chap12.htm#nerves

  44. "Neuropathy in Diabetes," by Richard C. Eastman, MD, is Chapter 15 of Diabetes in America, 2nd Edition. The URL is
    http://diabetes-in-america.s-3.com/adobe/chpt15.pdf

  45. Diabetic Neuropathy is an article provided by the Southeast Pain Management Services PLLC. The URL is
    http://www.paincareplus.com/diabetic.htm

  46. The Neurological Role of Antioxidants is a December 1997 research summary. The URL is
    http://www.veris-online.org/neurors.htm

  47. Efamol Nutraceuticals Inc., based in Kentville, Nova Scotia, Canada, is owned by QuantaNova Canada (above). The URL is
    http://www.efamol.com/

  48. The DFAN Charcot Foot Page is about a foot condition that affects people with diabetes. It is a serious condition since people with diabetes can lose some of the feeling in their feet due to neuropathy and literally crush their own joints. The URL is
    http://www.geocities.com/hotsprings/resort/3146/charcot/

  49. Peripheral Neuropathy is the Ontario HIV Clinics' Fact Sheet on the condition. The URL is
    http://www.tthhivclinic.com/perineur.htm

  50. "Diabetic Neuropathy of the Foot" is a pretty gruesome photo essay from the December 1995 issue of Dermatology Online Journal. The URL is
    http://matrix.ucdavis.edu/DOJvol1num2/diabetes/neuropathy.html

  51. "Learning About Foot Care" offers a number of resources on proper footcare, with the goal of preventing amputations. The URL is
    http://www.diabetesresource.com/html/pain.htm

  52. Aurogen Inc. in Fort Collins, Colorado, focuses on neurotropic insulin-like growth factor (IGF) hormones to treat diabetic neuropathy. The URL is
    http://www.aurogen.com/

  53. GroPep Ltd. in Adelaide, Australia, seems to have a similar emphasis to that of Aurogen. The company announced in September 2001 that it completed Phase 2 trials of PV705, a topical formulation of IGF-I for the treatment of diabetic neuropathy. The URL is
    http://www2.gropep.com.au/files/0901clintrial.pdf

  54. Diabetes and Foot Pain is the Diabetes Monitor's excellent discussion of how to deal with this effect of diabetic neuropathy. The URL is
    http://www.diabetesmonitor.com/dm-feet.htm

  55. CenterWatch Inc. lists dozens of clinical trials for diabetic neuropathy at
    http://www.centerwatch.com/patient/studies/cat253.html

  56. Diabetes and Nerve Disease is an online educational publication of the Juvenile Diabetes Foundation International. The URL is
    http://www.jdfcure.org/brch16.htm


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Since this information is constantly changing, readers are urged to email corrections and updates to me at mendosa@mendosa.com.

If you have a question about your health, please go to either Diabetes Questions & Answers at the Diabetes Monitor, or use the Question Form for the Diabetes Team at Children with Diabetes.


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