Diabetic peripheral neuropathy (DPN) is one of the most common chronic microvascular complications of diabetes mellitus and results from prolonged hyperglycaemia causing metabolic, vascular, and oxidative damage to peripheral nerves. The most common form is distal symmetric polyneuropathy, which typically begins in the feet and gradually progresses proximally in a stocking–glove distribution. Diabetic peripheral neuropathy is a major cause of chronic neuropathic pain, foot ulceration, lower-limb amputation, and reduced quality of life. Because early disease may be asymptomatic, all patients with type 2 diabetes mellitus should be screened for distal symmetric polyneuropathy at diagnosis and at least annually thereafter.

Pathophysiology

Persistent hyperglycaemia activates several metabolic pathways, including the polyol pathway, formation of advanced glycation end-products, oxidative stress, and chronic inflammation, leading to microvascular insufficiency and direct injury to peripheral nerve fibers. Reduced blood flow to the vasa nervorum impairs nerve oxygenation and nutrient supply, resulting in progressive axonal degeneration and segmental demyelination. Sensory nerve fibers are affected first, producing pain, numbness, and loss of protective sensation. As the disease progresses, motor and autonomic nerves may also become involved, leading to muscle weakness, foot deformities, gait instability, and autonomic dysfunction such as gastroparesis.

Risk Factors

• Long duration of diabetes mellitus

• Poor glycaemic control

• Older age

• Hypertension

• Dyslipidaemia

• Obesity

• Smoking

• Excessive alcohol consumption

• Chronic kidney disease

• Vitamin B12 deficiency (particularly in long-term metformin users)

• Previous diabetic foot ulcer or lower-limb amputation

Clinical Features

Sensory manifestations

• Burning pain in the feet or legs

• Aching pain or tenderness, especially at rest or during the night

• Tingling or prickling sensations

• Numbness of the feet and legs

• Electric shock-like sensations

• Reduced sensation to pain, temperature, or touch

• Stocking–glove distribution of symptoms

Motor manifestations

• Unsteady gait

• Weakness of the foot muscles

• Foot deformities

• Reduced balance

Autonomic manifestations

• Dry skin with reduced sweating

• Warm feet due to autonomic dysfunction

• Gastroparesis

• Orthostatic hypotension

Diagnostic Criteria

The diagnosis is primarily clinical and supported by neurological examination.

Suggestive clinical features include:

• Unsteady gait

• Burning, aching pain or tenderness in the legs or feet, particularly at rest or during the night

• Prickling or tingling sensations affecting the feet and legs in a stocking–glove distribution

• Numbness involving the distal lower limbs

• Previous foot ulceration or lower-limb amputation

• Loss of protective sensation on examination

Investigations

All patients should undergo annual foot assessment including:

Neurological assessment

• Pressure sensation using a 10 g monofilament

• Light-touch sensation using cotton wool

• Vibration sensation using a 128 Hz tuning fork

• Assessment of ankle reflexes where appropriate

Vascular assessment

• Peripheral pulses (dorsalis pedis and posterior tibial arteries)

• Assessment for postural hypotension

Foot examination

• Inspection for deformities

• Calluses

• Skin changes

• Foot ulceration

• Infection

• Appropriate footwear assessment

Additional investigations may be performed when another cause of neuropathy is suspected, including vitamin B12 level, renal function tests, thyroid function tests, and nerve conduction studies.

Management

Treatment Goals

• Relieve neuropathic pain

• Prevent foot ulceration

• Prevent lower-limb amputation

• Preserve mobility

• Improve quality of life

• Slow progression of neuropathy through optimal glycaemic control

Non-Pharmacological Management

• Achieve and maintain optimal glycaemic control

• Daily self-inspection of the feet

• Regular comprehensive foot examination

• Wear appropriate well-fitting protective footwear

• Avoid walking barefoot

• Smoking cessation

• Weight reduction where appropriate

• Regular physical activity

• Prompt treatment of minor foot injuries

• Patient education on diabetic foot care and prevention of ulceration

Pharmacological Management

Painful diabetic peripheral neuropathy

Pregabalin (PO) 75–150 mg once or twice daily for 4 weeks

Tricyclic antidepressants may also be beneficial:

Amitriptyline (PO) 25–75 mg once daily

OR

Imipramine (PO) 100 mg once daily

Treatment should be individualized according to symptom severity, treatment response, age, and adverse effects.

Gastroparesis (Autonomic Neuropathy)

Autonomic neuropathy affecting the gastrointestinal tract may present with delayed gastric emptying, nausea, vomiting, early satiety, abdominal bloating, and poor glycaemic control.

Recommended treatment:

Metoclopramide (PO) 10 mg every 8 hours

OR

Domperidone (PO) 10 mg every 8 hours

Diabetic Foot Care

Patients should receive:

• Foot care education

• Advice on appropriate footwear

• Regular foot inspection

• Early treatment of ulcers and infections

• Referral for specialist foot care when indicated

Prevention

The risk of diabetic peripheral neuropathy can be reduced through early and sustained glycaemic control, regular physical activity, smoking cessation, healthy nutrition, weight management, and routine annual neuropathy screening. Daily foot inspection, proper foot hygiene, appropriate footwear, and early management of foot injuries are essential to prevent foot ulceration and lower-limb amputation. Patients should be educated to seek immediate medical attention for any foot wound, swelling, redness, or signs of infection.

Outcome

Early detection and appropriate management of diabetic peripheral neuropathy can significantly reduce neuropathic pain, prevent foot ulceration and lower-limb amputation, preserve mobility, and improve quality of life. Although established nerve damage is often irreversible, optimal glycaemic control, regular foot care, patient education, and appropriate pharmacological treatment can slow disease progression, reduce complications, and improve long-term functional outcomes.