SUMMARY: 

Diabetic neuropathy is a common complication of diabetes that affects nearly 50% of patients with diabetes during their lifetimes. Incidence increases with longer duration of diabetes and poor glycemic control. Diabetic neuropathy can lead to pain, tingling, and loss of sensation, which can increase the risk of foot ulcers and infections, and eventually result in limb amputation. Proper management and treatment of diabetic neuropathy is crucial to prevent further damage and improve the quality of life for those living with this condition.  

Diagnosis and Presentation  

• Patients with DM should be regularly assessed for the development of peripheral neuropathy 
  • AAD recommends initial assessment at the time of diagnosis for DM2 and five years after diagnosis of DM1 
  • Assessment should be repeated at least annually thereafter  
• Diabetic neuropathy is a diagnosis of exclusion and other causes of neuropathy should be ruled out, such as:  
  • B12 deficiency  
  • HIV infection 
  • Uremic polyneuropathy  
  • Hypothyroidism 
  • Lyme disease  
  • Amyloidosis  
  • Critical illness  
  • Toxin (e.g., alcohol, chemotherapy, heavy metals)  
• Risk factors for diabetic neuropathy include: Longer duration of DM | Poor glycemic control | HLD | Smoking | Obesity | HTN | Chronic alcohol use | Older age  
• Diabetic neuropathy is typically a polyneuropathy that is: Symmetric | Distal | Sensory  
  • Large fiber damage results in loss of vibration and proprioception  
  • Small fiber damage results in loss of temperature, pain and light touch sensation  
• Exam for diagnosis should include: 
  • Relevant clinical history  
  • Temperature or pinprick sensation (small-fiber function) 
  • Vibration sensation using a 128-Hz tuning fork (large-fiber function) 
• Neuropathic pain is often the presenting symptom of diabetic neuropathy and is described a burning or electric shock like pain 
  • Can occur with paresthesia   
  • Often worse as night 
  • Associated with hyperalgesia and allodynia (i.e., pain worsens when putting on socks) 
• Electrophysiological testing or referral to a neurologist is rarely needed for diagnosis 
  • Can be done in cases of clinical uncertainty  

Treatment 

• Patients should be counseled that complete resolution of pain with treatment is unlikely 
• Clinical trials of approved medications used a 30% pain reduction as a successful outcome  
• Given limited efficacy with therapy, prevention of the development and progression of diabetic neuropathy is key 
  • Focus on glycemic control and management of risk factors e.g., tobacco and alcohol use | Healthy lifestyle choices | Blood pressure control
  • Physicians should assess patients for concurrent mood and sleep disorders  
  • Mood and sleep disorders can alter patient’s perception of pain 
  • Treatment may be tailored to also treat co-morbid conditions (e.g., SNRIs for patients with diabetic neuropathy and depression)  

Pharmacologic 

• Dose adjustment for the level of renal function is required for many of the drugs below and must be reviewed before prescribing 
• Suggested dosing is taken from AAN guidelines, and higher and lower dosages may be reasonable based on the patient and their co-morbid conditions  
• Gabapentinoids 
  • Can cause peripheral edema, use cautiously in patients with concurrent liver, renal and/or heart disease  
  • Gabapentin: 900 to 3600 mg/d  
  • Pregabalin (Lyrica): 300 to 600 mg/d 
  • Mirogabalin (Tarlige): 15 to 30 mg/d 
• SNRIs 
  • GI side effects may limit use  
  • Duloxetine (Cymbalta): 40 to 60 mg/d 
  • Desvenlafaxine (Pristiq): 200mg/d 
  • Venlafaxine (Effexor): 150 to 225mg/d  
• Tricyclic antidepressant  
  • Anti-cholinergic effects may limit use 
  • Avoid in patients with difficulty with urinary retention, orthostatic hypotension  
  • Amitriptyline (Elavil):  75 to 150 mg/d 
• Sodium channel blockers 
  • Lamotrigine (Lamictal): 200 to 400 mg/d 
  • Lacosamide (Vimpat): 400mg/d 
  • Oxcarbazepine (Trileptal): 1,400 to 1,800 mg/d 
  • Valproic acid (Depakote): 1,000 to 1,200 mg/d or 20 mg/kg/d | Teratogenic | Significant adverse effects and should not be offered unless multiple other medications have failed  
• Topical  
  • Capsaicin: 8% for 30 min/application or 0.075% 4 times per day | May have application site skin reactions  

Non-Pharmacologic 

• Cognitive behavioral therapy (CBT)  
  • Evidence for use of CBT for chronic pain is robust, and research is ongoing for the use of CBT for neuropathic pain  
• Patients who prefer non-pharmacologic methods can also be offered: Mindfulness | Tai Chi | Exercise  
  • Outside of patient’s personal preference, these should not be offered as first line monotherapies  

Not Recommended  

• Opioids | Tramadol | Tapentadol 
  • Benefits of pain control are vastly outweighed by serious risks including drug overdose and opioid dependence  
  • Given the safety profile of these drugs and lack of evidence of improved outcomes with long term use, they are not recommended  

Follow Up Care  

• Multiple pharmacologic agents may need to be tried before the patient finds a regimen that improves their pain 
• The typical duration of treatment in which efficacy is demonstrated is approximately 12 weeks 
  • An intervention to improve pain should be considered a failure when it is either ineffective after 12 weeks or side effects make continued use intolerable  
• If only partial pain relief is acquired with a drug in one class, a drug in a second class may be added for greater combined efficacy  

KEY POINTS: 

• Diabetic neuropathy is a common complication of diabetes that can lead to uncontrolled pain, disability, and eventual limb amputation 
• Prevention of diabetic neuropathy with strict glycemic control is crucial as the pain and progression of diabetic neuropathy is difficult to control once it begins  
• SNRIs, gabapentinoids, TCAs and sodium channel blockers all have efficacy in the treatment of diabetic neuropathy 
• Patients should be counseled that these medications can improve pain levels, but are unlikely to drop their pain to zero  

Learn More – Primary Sources 

AAN: Oral and topical treatment of painful diabetic polyneuropathy practice guideline update 

Diabetic Neuropathy: A Position Statement by the American Diabetes Association