About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Distal symmetric polyneuropathy (DSPN) = most common form (75%). Glove-and-stocking sensory loss, starting distally
- Annual foot screening: 10 g monofilament + ankle reflexes + peripheral pulse palpation. Stratify risk (low/moderate/high)
- Autonomic neuropathy: gastroparesis, postural hypotension, erectile dysfunction, bladder dysfunction, cardiovascular denervation
- Neuropathic pain: first-line amitriptyline, duloxetine, gabapentin, or pregabalin (NICE CG173). Combine if monotherapy insufficient
- Key prevention: optimise glycaemic control (HbA1c ≤48 in T1DM, individualised in T2DM). Tighter control in T1DM prevents neuropathy progression
- Diabetic foot: neuropathy + PVD → ulceration, infection, Charcot arthropathy, amputation. Multidisciplinary foot team
Overview
Diabetic neuropathy is nerve damage attributable to diabetes mellitus, affecting up to 50% of patients over their lifetime. The most common form is distal symmetric polyneuropathy (DSPN), a length-dependent sensorimotor neuropathy that starts in the toes and progresses proximally in a "stocking" then "glove" pattern. Other forms include autonomic neuropathy (affecting cardiovascular, GI, genitourinary, and sudomotor systems), mononeuropathies (cranial nerve palsies — III, IV, VI), diabetic amyotrophy (proximal motor neuropathy — severe thigh pain and wasting), and treatment-related neuropathy (painful small fibre neuropathy triggered by rapid glycaemic correction). The pathogenesis involves metabolic (polyol pathway, AGEs, oxidative stress) and microvascular mechanisms. Neuropathy is the leading contributor to diabetic foot disease, the most common reason for non-traumatic lower limb amputation in the UK.
Epidemiology
Approximately 30–50% of all diabetes patients develop some form of neuropathy. DSPN prevalence increases with disease duration and poor glycaemic control — present in approximately 10% at T2DM diagnosis and 50% after 25 years. It is present at diagnosis in up to 10% of T2DM (reflecting pre-diagnostic hyperglycaemia). Painful DSPN affects approximately 15–25% of diabetic patients. Autonomic neuropathy is often underdiagnosed — erectile dysfunction affects up to 50% of diabetic men. The UK performs approximately 8,000 diabetes-related amputations per year, the majority preventable with proper screening and foot care.
Clinical Features
Symptoms
DSPN: numbness, tingling, "pins and needles" in feet progressing to hands
Burning, stabbing, or shooting neuropathic pain (worse at night)
Painless injuries noticed late (burn, blister, ulcer) — "negative" symptoms
Unsteadiness and falls (proprioceptive loss)
Autonomic — GI: early satiety, bloating, vomiting (gastroparesis), diarrhoea (especially nocturnal), constipation
Autonomic — CV: postural dizziness, syncope (orthostatic hypotension), resting tachycardia
Autonomic — GU: erectile dysfunction, bladder distension, urinary retention, recurrent UTIs
Autonomic — sudomotor: anhidrosis (dry feet → fissuring → infection risk), gustatory sweating
Signs
Reduced sensation to 10 g monofilament (plantar surface of foot)
Reduced vibration sense (128 Hz tuning fork at hallux)
Absent ankle jerks (often earliest reflex change)
Glove-and-stocking sensory loss (all modalities in advanced disease)
Postural hypotension (systolic drop ≥20 mmHg on standing) without compensatory tachycardia
Charcot foot: red, hot, swollen foot (acute) → deformity, rocker-bottom sole (chronic). Often painless
Foot ulceration, callus formation, dry cracked skin
Investigations
First-line
Annual structured foot assessment10 g monofilament testing (3–4 plantar sites per foot), ankle reflexes, pedal pulse palpation (DP + PT), inspection for deformity/skin changes
Risk stratificationLow risk (normal sensation, palpable pulses), Moderate risk (one of: neuropathy, absent pulses, deformity), High risk (neuropathy + absent pulses or deformity, previous ulcer/amputation, Charcot)
Second-line
HbA1cAssess glycaemic control — tighter control slows neuropathy progression (especially in T1DM)
B12 levelMetformin use causes B12 deficiency which can mimic/worsen peripheral neuropathy. Check every 2–3 years if on metformin
TFTs, U&Es, LFTs, FBC, vitamin B12/folateExclude other causes of peripheral neuropathy
Specialist
Nerve conduction studiesIf atypical presentation (asymmetric, rapid onset, upper limb dominant, motor predominant)
Ankle-brachial pressure index (ABPI)Assess peripheral arterial disease — often coexistent. ABPI <0.8 = significant PAD
Gastric emptying studyIf gastroparesis suspected (scintigraphy or breath test)
1
Glycaemic control (prevention)
- Optimise HbA1c — tighter control reduces neuropathy risk/progression (DCCT/UKPDS evidence)
- Address other modifiable risk factors: smoking, alcohol, hypertension, dyslipidaemia
2
Neuropathic pain management (NICE CG173)
- First-line: amitriptyline 10–75 mg nocte, OR duloxetine 60–120 mg/day, OR gabapentin 300–3600 mg/day, OR pregabalin 150–600 mg/day
- Try one agent at adequate dose for ≥8 weeks before switching
- If monotherapy insufficient: combine two agents from different classes
- Tramadol as rescue analgesia. Capsaicin cream 0.075% topically for localised pain
- Avoid simple analgesics (paracetamol, NSAIDs) — generally ineffective for neuropathic pain
3
Diabetic foot management
- Annual structured foot assessment for ALL diabetes patients
- High-risk patients: referral to multidisciplinary diabetic foot team (podiatry, diabetologist, vascular surgery, orthotics)
- Patient education: daily foot inspection, appropriate footwear, avoid walking barefoot, report any new ulcer/discolouration urgently
- Active foot ulcer: offloading (total contact cast/removable walker), debridement, wound care, antibiotics if infected
- Charcot foot: urgent referral. Immobilisation (non-weight-bearing cast). Do NOT mistake for cellulitis/gout
4
Autonomic neuropathy
- Gastroparesis: dietary modification (small frequent meals, low fat/fibre), prokinetics (metoclopramide, domperidone — short courses), erythromycin (motilin agonist)
- Orthostatic hypotension: stand slowly, compression stockings, adequate fluid/salt intake, fludrocortisone, midodrine
- Erectile dysfunction: PDE5 inhibitors (sildenafil, tadalafil) first-line
- Bladder dysfunction: timed voiding, intermittent self-catheterisation
Complications
- Diabetic foot ulceration: Neuropathy (loss of protective sensation) + PVD (poor healing) → ulceration → infection → osteomyelitis → amputation
- Charcot neuroarthropathy: Neuropathic destruction of foot joints → rocker-bottom deformity, fractures, collapse. Can be limb-threatening
- Falls and injuries: Proprioceptive loss + postural hypotension
- Silent MI: Cardiac autonomic neuropathy masks ischaemic pain — increased sudden cardiac death risk
- Gastroparesis: Erratic glucose absorption → unpredictable glycaemic control → recurrent hypo/hyperglycaemia
UKMLA Exam Tips
- 1Glove-and-stocking distribution = length-dependent. Starts in toes (longest nerves affected first) and progresses proximally
- 210 g monofilament is the standard screening tool — reduced sensation = increased foot ulceration risk
- 3Charcot foot: red, hot, swollen, painless foot in a diabetic → DO NOT mistake for cellulitis or gout. X-ray + urgent specialist referral
- 4Neuropathic pain: amitriptyline, duloxetine, gabapentin, pregabalin — know these as first-line options (NICE CG173)
- 5Metformin causes B12 deficiency which worsens neuropathy — check B12 every 2–3 years
- 6Cranial nerve III palsy in diabetes: pupil-SPARING (microvascular). Pupil-INVOLVING = compressive (PCA aneurysm) — urgent imaging
- 7Diabetic amyotrophy: severe proximal thigh pain + quadriceps wasting in elderly T2DM — usually self-limiting over months
practicetest your knowledge on diabetic neuropathyApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — endocrine and beyond.
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