Peripheral neuropathy (diabetic and other) !

Peripheral neuropathy is damage to nerves outside the brain and spinal cord, most often from diabetes, causing numbness, pain and weakness in the feet first.

Updated 2026-11-01

Structures involved

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In the clinical exam

Why it happens

What it is

Damage to the peripheral nerves that causes sensory, motor or autonomic symptoms. The commonest pattern is a length-dependent, symmetric polyneuropathy beginning in the feet; diabetes is the leading cause, followed by alcohol, vitamin B12 deficiency, toxins and inherited forms.

Who gets it

Diabetic neuropathy affects a large share of people with long-standing diabetes and is the main path to foot ulcers and amputation in Colombia and Latin America. Leprosy and HIV remain additional causes in the region.

Causes

Diabetes mellitus (and prediabetes): the most common cause
Alcohol use disorder, often with poor nutrition
Vitamin B12 deficiency (pernicious anaemia, metformin use, strict vegan diet)
Toxic: chemotherapy, isoniazid, heavy metals
Hereditary: Charcot-Marie-Tooth disease
Others: hypothyroidism, chronic kidney disease, HIV, leprosy, vasculitis, Guillain-Barré syndrome

Risk factors

Long duration and poor control of diabetes
Hypertension, dyslipidaemia, obesity and smoking
Heavy alcohol intake
Older age and taller height
Long-term metformin or acid-suppressing drugs (B12 deficiency)

Pathophysiology

In diabetes, chronic hyperglycaemia damages the nerve through metabolic and oxidative stress, advanced glycation end products and injury to the small vessels that feed the nerves. The longest axons fail first, giving a stocking-and-glove pattern. Small fibres carry pain and temperature, large fibres carry vibration and position sense, and autonomic fibres control the heart, gut, bladder and sweating.

Classification

Distal symmetric polyneuropathy (most common)
Autonomic neuropathy: cardiovascular, gastrointestinal (gastroparesis), genitourinary, sudomotor
Focal and multifocal: mononeuropathies (median, fibular, cranial III) and diabetic amyotrophy (lumbosacral radiculoplexus neuropathy)
By fibre: small-fibre, large-fibre or mixed

Symptoms and signs

Numbness, tingling or burning in the feet, spreading upward in a stocking-and-glove pattern
Neuropathic pain, often worse at night
Loss of balance and falls from reduced position sense
Weakness of the foot muscles, foot deformity
Autonomic: dizziness on standing, early satiety and vomiting (gastroparesis), diarrhoea or constipation, erectile dysfunction, bladder dysfunction, abnormal sweating

Diagnosis

Clinical: History and examination: 10-g monofilament, vibration with a 128-Hz tuning fork, pinprick, temperature, ankle reflexes, plus foot inspection. Orthostatic blood pressure for autonomic involvement. Yearly screening is standard in diabetes.
Tests: Glucose and HbA1c, vitamin B12 (with methylmalonic acid if borderline), TSH, kidney function, and serum protein electrophoresis as a basic workup. Nerve conduction studies when the presentation is atypical; gastric emptying study for suspected gastroparesis.
Imaging: Not routine. MRI when a radiculopathy or plexus lesion is suspected; foot X-ray or MRI for Charcot foot or osteomyelitis.

Differential diagnosis

Lumbar spinal stenosis or radiculopathy
Myelopathy, including B12-related subacute combined degeneration
Peripheral artery disease
Restless legs syndrome
Entrapment neuropathy (tarsal tunnel, carpal tunnel)

Goal of treatment

Slow progression by treating the cause, relieve neuropathic pain, and prevent foot ulcers, falls and autonomic complications.

Treatment

Medical: Treat the cause: optimise glucose, blood pressure and lipids in diabetes; vitamin B12 replacement; stop alcohol or the toxic drug; thiamine in alcohol-related cases.
Medical: Neuropathic pain: gabapentinoids (pregabalin, gabapentin), serotonin-noradrenaline reuptake inhibitors (duloxetine) or tricyclic antidepressants (amitriptyline); topical capsaicin.
Medical: Autonomic symptoms: prokinetics and small frequent meals for gastroparesis; volume and compression measures for orthostatic hypotension; phosphodiesterase-5 inhibitors for erectile dysfunction.
Follow-up: Annual foot exam, daily self-inspection of the feet and protective footwear; nursing priorities are foot care education, fall prevention and checking water temperature before bathing.
Rehabilitation: Physiotherapy for balance and strength, and orthotics for foot deformity or foot drop.

Complications

Foot ulcers, infection and amputation
Charcot neuroarthropathy
Falls and fractures
Silent myocardial ischaemia and sudden death in cardiac autonomic neuropathy
Malnutrition and erratic glucose from gastroparesis

Prognosis

Established diabetic neuropathy rarely reverses, but good control of glucose and vascular risk factors slows it, and foot care prevents most amputations. Neuropathies from B12 deficiency or alcohol may improve if treated early.

Prevention

Early and sustained glucose control, especially in type 1 diabetes
Control of blood pressure, lipids and weight, and not smoking
B12 checks in people on long-term metformin
Limiting alcohol

Test yourself

Think of the answer, then tap the question to see it.

What is the most common pattern of diabetic neuropathy?

Distal symmetric sensorimotor polyneuropathy in a stocking-and-glove distribution.

Which bedside test identifies feet at risk of ulceration?

The 10-g monofilament, often combined with vibration testing using a 128-Hz tuning fork.

Which diabetes drug can cause B12 deficiency and worsen neuropathy?

Metformin, with long-term use.

What are classic features of diabetic gastroparesis?

Early satiety, nausea, vomiting of undigested food, bloating and erratic glucose control.

Which drug classes are first-line for painful diabetic neuropathy?

Gabapentinoids, SNRIs such as duloxetine, and tricyclic antidepressants.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Peripheral neuropathy (MedlinePlus Medical Encyclopedia (U.S. National Library of Medicine), 2026); Diabetes and nerve damage (MedlinePlus Medical Encyclopedia (U.S. National Library of Medicine), 2025).

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Representative model, for educational purposes only.

Sciatic nerve highlighted on the Durgical 3D model