Diabetic Neuropathy

1. Epidemiology
   1. Occurs in Type I and Type II Diabetes Mellitus
   2. Occurs in 42% of Type II Diabetes Mellitus
      1. Onset within 10 years of disease
      2. Higher risk with higher Glycosylated Hemoglobin
      3. Partanen (1995) N Engl J Med 333:89-94
2. Types
   1. Bilateral Peripheral Polyneuropathy in Diabetes
   2. Diabetic Focal Neuropathy
   3. Diabetic Autonomic Neuropathy
3. Diagnosis
   1. See also Peripheral Neuropathy Testing
4. Differential Diagnosis
   1. See Leg Pain
   2. See Autonomic Neuropathy
   3. Peripheral Polyneuropathy
      1. Vitamin B12 Deficiency
         1. Especially when using Metformin
      2. Folic Acid deficiency
      3. Iron Deficiency Anemia
      4. Hypothyroidism
      5. Uremia
      6. Chemical Toxin exposure (heavy metal toxicity)
      7. Alcohol Abuse
      8. Sarcoidosis
      9. Leprosy
      10. Periarteritis nodosum
      11. Systemic Lupus Erythematosus
      12. Leukemia
   4. Other important causes of Leg Pain
      1. Lumbar Disc Disease with radiculopathy
      2. Lumbar central spinal stenosis
      3. Claudication
      4. Night Cramps
      5. Restless Leg Syndrome
      6. Degenerative Joint Disease
         1. Hip Osteoarthritis
         2. Knee Osteoarthritis
         3. AnkleOsteoarthritis
5. Complications (of distal symmetric Polyneuropathy)
   1. See Charcot Foot
   2. See Foot Wound
   3. See Suspected Osteomyelitis in Diabetes Mellitus
   4. See Peripheral Neuropathy Tremor
6. Management: Approach
   1. See dosing regimens in next section
   2. Step 1
      1. See prevention below for diabetes care optimization
      2. Evaluate for other causes of Peripheral Neuropathy (see differential diagnosis above)
   3. Step 2
      1. Tricyclic Antidepressants (Amitriptyline, Nortriptyline)
   4. Step 3
      1. Anticonvulsants
   5. Step 4
      1. Serotonin-Norepinephrine reuptake inhibitors
   6. Step 5
      1. Reconsider differential diagnosis
      2. Chronic Analgesics (Opioids, Tramadol)
      3. Consider pain management referral
   7. Adjuncts (add at any point)
      1. Topical Lidocaine (Lidoderm)
      2. Capsaicin cream
      3. Acupuncture
7. Management: Medications for Painful Peripheral Neuropathy
   1. Tricyclic Antidepressants
      1. May be more effective in burning, steady pain
      2. Amitriptyline (Elavil) started at 10-30 mg at bedtime and increased to 50-75 mg (maximum 150 mg) at bedtime
      3. Nortriptyline (Pamelor) started at 10-30 mg at bedtime and increased to 50-75 mg (maximum 150 mg) at bedtime
      4. Desipramine (Norpramin) starting at 25 mg at bedtime
   2. Anticonvulsants
      1. May be more effective in sharp lancinating pain
      2. Gabapentin (Neurontin)
         1. Start at 100 mg at bedtime to 100 mg orally three time daily
         2. Advance to 300 orally three times daily (maximum 1200 mg three times daily)
      3. Pregabalin (Lyrica)
         1. Very similar to Gabapentin
         2. Start at 50 mg orally two to three times daily
         3. Titrate to 100 mg orally three times daily or 150 mg twice daily (maximum 300 mg twice daily)
      4. Carbamazepine (Tegretol)
         1. Start at 100 mg orally twice daily
         2. Advance to 200 mg orally twice daily as tolerated (maximum 600 mg twice daily)
         3. Requires Complete Blood Count monitoring
   3. Serotonin-Norepinephrine Reuptake Inhibitors
      1. Duloxetine (Cymbalta)
         1. Start at 20 mg twice daily
         2. Advance to 60 mg daily (or divided 30 mg twice daily)
      2. Venlafaxine (Effexor)
         1. Extended release (preferred): Venlafaxine XR 37.5 mg daily (titrate to 225 mg daily)
         2. Regular (generic): Venlafaxine 37.5 mg twice daily (titrate to 225 mg divided twice daily)
   4. Topical pain management
      1. TENS Unit
      2. Lidocaine 5% patch (Lidoderm) up to 3 patches applied daily to affected area (applied for no more than 12 hours daily)
      3. Capsaicin 0.075% cream applied to affected area twice daily (start with small amount and slowly increase)
   5. Analgesics
      1. NSAIDS are not typically recommended in Diabetes Mellitus due to renal, gastrointestinal and cardiovascular risks
      2. Tramadol (Ultram)
      3. Opioids (avoid unless no other option available)
8. Prevention
   1. See Diabetic Foot Care
   2. Optimize Diabetes Mellitus management (Hemoglobin A1C <7-8%)
   3. Optimize Hypertension and Hyperlipidemia Management
9. References
   1. Aring (2005) Am Fam Physician 71:2123-30
   2. Backonja (1998) JAMA 280:1831-36
   3. Kochar (2004) QJM 97:33-8
   4. Lindsay (2010) Am Fam Physician 82(2): 151-8
   5. Lipnick (1996) Am Fam Physician 54(8):2478-84
   6. McQuay (1996) Pain 68:217-27
   7. Simmons (2000) Clinical Diabetes 18:116-7
   8. Sindrup (1990) Pain 42:135-44
   9. Veves (2008) Pain Med 9(6): 660-74
   10. Wong (2007) BMJ 335(7610): 87