Diabetic Neuropathy

Aka: Diabetic Neuropathy, Peripheral Neuropathy in Diabetes Mellitus

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II. 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 [PubMed]

III. Types

  1. Bilateral Peripheral Polyneuropathy in Diabetes (Diabetic Distal Symmetric Polyneuropathy)
  2. Diabetic Focal Neuropathy (Diabetic Mononeuropathy)
  3. Diabetic Autonomic Neuropathy
  4. Diabetic Amyotrophy (Symmetric Diabetic Proximal Motor Neuropathy)

IV. Diagnosis

  1. See also Peripheral Neuropathy Testing

V. 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. Ankle Osteoarthritis

VI. 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

VII. Management: Approach

  1. See dosing regimens in next section
  2. Step 1
    1. See prevention below for diabetes care optimization including glycemic control
    2. Set realistic patient expectations (e.g. 30-50% symptom improvement with medications)
    3. Evaluate for other causes of Peripheral Neuropathy (see differential diagnosis above)
  3. Step 2
    1. Tricyclic Antidepressants (e.g. Amitriptyline, Nortriptyline, Desipramine): NNT 2-4
  4. Step 3
    1. Anticonvulsants (e.g. Gabapentin, Pregabalin): NNT 3-8
  5. Step 4
    1. Serotonin-Norepinephrine reuptake inhibitors (e.g. Duloxetine, Venlafaxine): NNT 4-11
  6. Step 5
    1. Reconsider differential diagnosis
    2. Chronic Analgesics (Opioids, Tramadol)
    3. Consider SSRI (e.g. Escitalopram), although lack of adequate studies to support use
    4. Consider pain management referral
  7. Adjuncts (add at any point)
    1. Topical Lidocaine (Lidoderm 5% patch) or the OTC, less expensive Lidocare 4% patch (but still expensive!)
    2. Capsaicin 0.075% cream (often intolerable due to burning)
    3. Transcutaneous electrical nerve stimulation (TENS)
    4. Isosorbide Dinitrate spray 30 mg applied to bottom of feet at bedtime
    5. Acupuncture (no large, high quality studies in Diabetic Neuropathy to support use)

VIII. Management: Medications for Painful Peripheral Neuropathy

  1. Tricyclic Antidepressants
    1. May be more effective in burning, steady pain
    2. Avoid in the elderly due to strong Anticholinergic effects (see Beers List)
    3. Amitriptyline (Elavil) or Nortriptyline (Pamelor)
      1. Started at 10-30 mg at bedtime
      2. Increase 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. Adjust for renal dysfunction
      2. Start at 100 mg at bedtime to 100 mg orally three time daily
      3. Advance to 300 orally three times daily (maximum 1200 mg three times daily)
    3. Pregabalin (Lyrica)
      1. Very similar to Gabapentin, but no generic yet available and expensive
      2. More convenient dosing (twice daily), and no Renal Dosing adjustment as contrasted with Gabapentin
      3. Start at 50 mg orally two to three times daily
      4. Titrate to 100 mg orally three times daily or 150 mg twice daily (maximum 300 mg twice daily)
    4. Other agents
      1. Other anticonvulsants (including Carbamazepine, Topiramate) do not have adequate evidence to support use
  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)
    4. Isosorbide Dinitrate spray 30 mg applied to bottom of feet at bedtime
  5. Analgesics
    1. NSAIDS are not typically recommended in Diabetes Mellitus
      1. Risk of renal, gastrointestinal and cardiovascular risks
    2. Tramadol (Ultram)
      1. See Tramadol for precautions (lower efficacy with adverse effect risk)
    3. Opioids (avoid unless no other option available)

IX. Prevention

  1. See Diabetic Foot Care
  2. Optimize Diabetes Mellitus management (Hemoglobin A1C <7-8%)
  3. Optimize Hypertension and Hyperlipidemia Management

X. References

  1. (2017) Presc Lett 24(9): 50
  2. Aring (2005) Am Fam Physician 71:2123-30 [PubMed]
  3. Backonja (1998) JAMA 280:1831-36 [PubMed]
  4. Kochar (2004) QJM 97:33-8 [PubMed]
  5. Lindsay (2010) Am Fam Physician 82(2): 151-8 [PubMed]
  6. Lipnick (1996) Am Fam Physician 54(8):2478-84 [PubMed]
  7. McQuay (1996) Pain 68:217-27 [PubMed]
  8. Simmons (2000) Clinical Diabetes 18:116-7 [PubMed]
  9. Sindrup (1990) Pain 42:135-44 [PubMed]
  10. Snyder (2016) Am Fam Physician 94(3): 227-34 [PubMed]
  11. Veves (2008) Pain Med 9(6): 660-74 [PubMed]
  12. Wong (2007) BMJ 335(7610): 87 [PubMed]

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Related Studies

Ontology: Diabetic Neuropathies (C0011882)

Definition (NCI) A chronic, pathological complication associated with diabetes mellitus, where nerve damages are incurred due to diabetic microvascular injury involving small blood vessels that supply these nerves, resulting in peripheral and/or autonomic nerve dysfunction.
Definition (MSH) Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)
Definition (CSP) common complication of diabetes mellitus in which nerves are damaged as a result of hyperglycemia (high blood sugar levels).
Concepts Disease or Syndrome (T047)
MSH D003929
ICD9 250.6
SnomedCT 267472008, 154683002, 193182005, 866003, 190349003, 190353001, 230572002
English Neuropathies, Diabetic, Neuropathy, Diabetic, Diab.mell. with neuropathy, Diabetic Neuropathies [Disease/Finding], Neuropathy;diabetic, diabetic nerve damage, diabetic neuropathies, Neuropathy - diabetic, Diabetes + neuropathy, Diabetes mellitus with neurological manifestation, Diabetes mellitus NOS with neurological manifestation (disorder), Diabetes mellitus NOS with neurological manifestation, Diabetic neuropathies, Diabetic neuropathy, Diabetes mellitus with neuropathy, Diabetic neuropathy (disorder), neuropathy; diabetes (manifestation), Diabetic neuropathy (disorder) [Ambiguous], Diabetic Neuropathies, Diabetic Neuropathy, Diabetes with neurological manifestations, diabetic neuropathy
Italian Neuropatia diabetica, Neuropatie diabetiche
Swedish Diabetesneuropatier
Czech diabetické neuropatie, Diabetická neuropatie
Finnish Diabeettiset neuropatiat
Russian DIABETICHESKIE NEVROPATII, DIABETICHESKAIA POLINEVROPATIIA, DIABETICHESKAIA AMIOTROFIIA, DIABETICHESKAIA NEVRALGIIA, DIABETICHESKAIA NEVROPATIIA AVTONOMNAIA, ДИАБЕТИЧЕСКАЯ АМИОТРОФИЯ, ДИАБЕТИЧЕСКАЯ НЕВРАЛГИЯ, ДИАБЕТИЧЕСКАЯ НЕВРОПАТИЯ АВТОНОМНАЯ, ДИАБЕТИЧЕСКАЯ ПОЛИНЕВРОПАТИЯ, ДИАБЕТИЧЕСКИЕ НЕВРОПАТИИ
Japanese ﾄｳﾆｮｳﾋﾞｮｳｾｲﾆｭｰﾛﾊﾟﾁｰ, 糖尿病性ニューロパチー, 糖尿病性ニューロパシー, 糖尿病ニューロパシー, 糖尿病神経障害, 神経障害-糖尿病性, 糖尿病性神経障害
Croatian DIJABETIČNE NEUROPATIJE
Polish Neuropatie cukrzycowe
Hungarian Diabeteses neuropathia
Norwegian Nervesykdommer ved diabetes, Diabetiske nervesykdommer, Diabetesnevropatier, Diabetiske nevropatier
Spanish diabetes mellitus, SAI con manifestaciones neurológicas, diabetes mellitus, SAI con manifestaciones neurológicas (trastorno), Acropatía Diabética Úlcero-Mutilante, diabetes mellitus con neuropatía, diabetes sacarina con neuropatía, neuropatía diabética (concepto no activo), neuropatía diabética (trastorno), neuropatía diabética, Neuropatía diabética, Neuropatías Diabéticas
Portuguese Acropatia Diabética Ulceromutilante, Neuropatia diabética, Neuropatias Diabéticas
Dutch neuropathie; diabetes, diabetische neuropathie, Diabetische neuropathie, Neuropathie, diabetische
French Neuropathie diabétique, Neuropathies diabétiques
German Diabetische Neuropathie, Diabetische Neuropathien
Derived from the NIH UMLS (Unified Medical Language System)

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