What is the treatment for polyneuropathy due to an underlying disease in adults, particularly those with diabetes?

Polyneuropathy Due to Underlying Disease

Polyneuropathy due to underlying disease—particularly diabetic polyneuropathy—requires aggressive glycemic control as the primary disease-modifying intervention, combined with systematic screening, risk factor management, and targeted pharmacotherapy for neuropathic pain when present. 1

Understanding the Condition

Polyneuropathy secondary to underlying disease most commonly refers to diabetic sensorimotor polyneuropathy (DSPN), which affects approximately one-third of people with diabetes. 2 The critical challenge is that up to 50% of cases are asymptomatic, yet these patients remain at high risk for foot ulceration and amputation. 1

Diabetic neuropathy is a diagnosis of exclusion—you must rule out other treatable causes including alcohol toxicity, vitamin B12 deficiency, hypothyroidism, renal disease, and medication-induced neuropathy before attributing symptoms solely to diabetes. 1

Disease-Modifying Treatment Approach

Glycemic Control: The Only Proven Disease-Modifying Therapy

Achieving near-normal blood glucose control is the single most effective intervention to prevent or delay neuropathy development. 1

• For Type 1 diabetes: Intensive glycemic control can effectively prevent diabetic peripheral neuropathy and cardiac autonomic neuropathy (Grade A evidence). 1
• For Type 2 diabetes: Glycemic control modestly slows progression but does not reverse established neuronal loss (Grade B evidence). 1
• Target HbA1c between 6-7% for most patients, implemented as early as possible in the disease course. 3

Additional Risk Factor Management

Beyond glucose control, address these modifiable factors to slow neuropathy progression:

• Blood pressure control: Hypertension independently accelerates neuropathy development and progression. 1
• Lipid management: Controlling dyslipidemia aids in preventing neuropathy progression, particularly in type 2 diabetes. 1
• Smoking cessation: Essential to reduce vascular complications that worsen neuropathy. 1, 3

Systematic Screening Protocol

Timing of Assessment

• Type 2 diabetes: Screen at diagnosis and annually thereafter. 1
• Type 1 diabetes: Screen 5 years after diagnosis and annually thereafter. 1
• Patients with other microvascular complications: Screen more frequently, as kidney disease correlates with higher neuropathy risk. 1

Clinical Examination Components

Perform these specific bedside tests annually:

1. Small-fiber function: Test pinprick and temperature sensation in feet and lower legs. 1
2. Large-fiber function: Assess vibration perception using a 128-Hz tuning fork and check lower-extremity reflexes. 1
3. Protective sensation: Perform 10-g monofilament testing at multiple foot sites to identify ulceration risk. 1

Electrophysiological testing is rarely needed except when clinical features are atypical, the diagnosis is unclear, or you suspect a non-diabetic cause. 1

Pharmacologic Treatment for Neuropathic Pain

First-Line Agents (Grade A Evidence)

When patients develop painful neuropathy, initiate one of these three medications: 1, 4

Pregabalin: 5

• Start at 50 mg three times daily (150 mg/day)
• Increase to 100 mg three times daily (300 mg/day) within 1 week based on tolerability
• Maximum dose: 300 mg/day (doses above this are not recommended due to increased adverse effects without additional benefit)
• Common side effects: dizziness, somnolence, peripheral edema, weight gain 5

Duloxetine: 4

• Start at 60 mg once daily
• May increase to 120 mg daily if needed
• Caution: May worsen glycemic control in some patients 6

Gabapentin: 4

• Start at 300 mg once daily
• Titrate to 300-1,200 mg three times daily as tolerated

Alternative Options (Grade B Evidence)

If first-line agents fail or are not tolerated: 4

• Tricyclic antidepressants (amitriptyline, nortriptyline, imipramine): 10-75 mg at bedtime
• Topical capsaicin cream: 0.025-0.075% applied three to four times daily

Critical Pitfall to Avoid

Do not use opioids for chronic neuropathic pain due to addiction risk and potential worsening of treatment adherence. 6 The evidence does not support their use as first-line or even second-line therapy.

Foot Care and Ulcer Prevention

Daily Patient Self-Care

Patients with confirmed neuropathy must: 3

• Visually inspect both feet daily for cuts, blisters, redness, swelling, calluses, or skin breakdown
• Use hand palpation to feel for warmth or pressure areas if vision is impaired
• Check between all toes for moisture, cracking, or fungal infections
• Apply moisturizing lotion to dry skin (but not between toes) to prevent cracking 3

Footwear Management

• Wear well-fitted walking shoes or athletic shoes that cushion and redistribute pressure. 1, 3
• Break in new shoes gradually over several days to minimize blister formation. 1, 3
• Consider extra-wide or depth shoes if bony deformities (hammertoes, bunions, prominent metatarsal heads) are present. 1
• Patients with severe Charcot deformities may require custom-molded shoes. 1

Professional Foot Care

• Visual foot inspection at every healthcare visit for patients with neuropathy. 1, 3
• Have calluses debrided by a trained foot care specialist—never attempt self-removal. 1, 3
• Treat minor conditions like tinea pedis promptly to prevent progression to serious infections. 1, 3
• Seek immediate medical attention for any foot wound, regardless of size, as healing is impaired and infection risk is high. 3

Autonomic Neuropathy Considerations

Screen for autonomic neuropathy symptoms starting at the same intervals as peripheral neuropathy: 1

• Ask about orthostatic dizziness, syncope, resting tachycardia
• Examine for orthostatic hypotension (drop >20 mmHg systolic or >10 mmHg diastolic upon standing)
• Look for dry, cracked skin in extremities
• Inquire about gastrointestinal symptoms (gastroparesis, diarrhea, constipation)
• Assess for hypoglycemia unawareness 4

Cardiovascular autonomic neuropathy significantly increases mortality risk and requires careful cardiac evaluation and monitoring. 4

Treatment Algorithm Summary

1. Confirm diagnosis: Rule out non-diabetic causes (B12 deficiency, hypothyroidism, alcohol, medications)
2. Optimize glycemic control: Target HbA1c 6-7% as early as possible
3. Manage cardiovascular risk factors: Blood pressure, lipids, smoking cessation
4. Screen systematically: Annual monofilament testing, vibration sense, pinprick/temperature
5. If painful neuropathy develops: Start pregabalin, duloxetine, or gabapentin
6. Implement foot care protocol: Daily inspection, proper footwear, professional callus care
7. Screen for autonomic involvement: Orthostatic symptoms, gastroparesis, hypoglycemia unawareness
8. Monitor annually: Reassess neuropathy progression and treatment efficacy