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Diabetic Neuropathy

Neda Frayha, MD and Harpreet Tsui, DO
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When a patient with poorly controlled diabetes presents with numbness and tingling in their feet, how well do we really know what to do next? To help us understand diabetic neuropathy a bit better, Dr. Harpreet Tsui joins Neda to discuss screening, diagnosis, and treatment pearls.

 

Pearls:

  • Prevention through good glycemic control and regular screening for diabetic neuropathy is key.

  • First-line treatment is pregabalin and duloxetine.

 

  • Background:

    • Types of diabetic neuropathy:

      • 1. Cardiovascular autonomic neuropathy

      • 2. Individual mononeuropathies

      • 3. Chronic inflammatory demyelinating polyneuropathy

      • 4. Distal symmetric polyneuropathy (DSPN, 75% of neuropathies)

    • 20% of those with type 1 diabetes will develop after 20 years

    • 50% of those with type 2 diabetes will develop after 10 years

    • Can lead to diabetic foot ulcers and Charcot’s foot

  • Diagnosis: clinical

    • History - burning, paresthesias that are worse at night, hyperalgesia, allodynia, numbness/tingling

    • Exam - 

      • Small fiber - pinprick and test for temperature sensation

      • Large fiber - monofilament testing

      • Ankle reflexes

      • Check out AFP 2014 article for a 3-minute comprehensive exam

    • Studies - 

      • No need for referral to neurology for EMG unless asymmetry, motor > sensory function loss, rapid progression

      • Rule out vitamin B issues and thyroid issues

  • Screening:

    • 50% of patients don’t have symptoms, which means routine screening (foot exam) is important

    • American Diabetes Association 2017 recommendations:

      • Screen five years after diagnosis of DM1 and at the diagnosis of DM2

      • Consider screening those with prediabetes who have any symptoms

  • Treatment:

    • First-line: pregabalin (per AAN)

      • In order patients, careful with side effects like dizziness, somnolence, peripheral edema

      • Dosing starts low at 25mg daily all the way up to 300mg max daily dosage

    • First-line: duloxetine (SNRI)

      • Side effects include somnolence, dizziness, constipation and decreased appetite

      • Max dose 60mg daily

    • Venlafaxine (SNRI)

      • Can lower seizure threshold

      • Gradual tapering is recommended

      • Dose 150-225mg daily

      • Cochrane Review 2015 showed not better than placebo but an option that may work for some patients

    • Gabapentin

      • Not great evidence on efficacy but available as a generic

      • Needs to be renally dosed

      • Effective in ranges of 1800-3600mg per day

    • Amitriptyline (TCA)

      • Not FDA-approved but small trials show improvement in pain

      • Desipramine and nortriptyline with similar efficacy

      • Increased risk of arrhythmia and myocardial infarction

    • Topical capsaicin

      • Some data showing efficacy

      • Common complaint of burning at site of application

    • Lidocaine

      • Limited data but worth a try

    • Alpha lipoic acid

      • Potent antioxidant thought to counteract the oxidative stress of diabetes on the nerves

      • Randomized control trial (SYDNEY 2) showed improvement in pain with 600mg daily 

    • Opioids

      • NOT indicated

 

REFERENCES:

  1. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2016;40(1):136-154. doi:10.2337/dc16-2042

  2. Miller J, Carter E, Shih J, Giovinco N. How to do a 3-minute diabetic foot exam. J Fam Pract. 2014;63(11). https://www.mdedge.com/familymedicine/article/88218/diabetes/how-do-3-minute-diabetic-foot-exam. Accessed January 13, 2020.

  3. Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;8. doi:10.1002/14651858.cd011091.pub2

  4. Ziegler D, Ametov A, Barinov A, et al. Oral Treatment With  -Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy: The SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365-2370. doi:10.2337/dc06-1216

  5. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758-1765. doi:10.1212/wnl.0b013e3182166ebe

  6. Bansal V. Diabetic neuropathy. Postgrad Med J. 2006;82(964):95-100. doi:10.1136/pgmj.2005.036137

  7. ‌Kasznicki J. State of the art papers Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy. Arch Med Sci. 2014;10(2):345-354. doi:10.5114/aoms.2014.42588

  8. Feldman, E. Management of diabetic neuropathy. In: Eichler A (Ed). UpToDate. https://www.uptodate.com/contents/management-of-diabetic-neuropathy

Kevin B., Mr. -

You recommend pregabalin as a first line therapy for diabetic neuropathy. However almost all insurances will not approve this med until you max out on gabapentin? Some patients do not tolerate even a small dose of gabapentin. How do you et around this, I have found prior authoriazation will still not okay pregabalin with our use of gabapentin first?

Neda F., MD -

Hi Kevin. Here is Dr. Tsui's response: "I agree for pregabalin approval, I often have to trial a patient on gabapentin first. So while the guidelines for diabetic neuropathy list pregabalin as first-line, the insurance companies dictate what they cover. If a patient cannot even tolerate gabapentin 100mg, I will write that in my prior authorization. I’ve had to go back and forth with the insurance companies but usually get pregabalin covered for some time."

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Primary Care RAP Written Summary April 2020 1 MB - PDF

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