Diabetic Neuropathy

Commonest cause of peripheral neuropathy in the UK. Affects ~50% of diabetic patients. Distal symmetric polyneuropathy is the predominant form. Major risk factor for diabetic foot ulceration and amputation. Prevention through glycaemic control is key (DCCT/UKPDS trials).

Key Facts

Commonest cause of neuropathy in UK: affects ~50% of patients with diabetes; major contributor to diabetic foot disease Distal symmetric polyneuropathy (DSPN): most common form (~75%); length-dependent sensory > motor; glove-and-stocking distribution Painful diabetic neuropathy: affects ~25% of diabetic patients; burning, shooting, lancinating pain; worse at night Other forms: autonomic neuropathy, diabetic amyotrophy (proximal motor), mononeuropathies (CN III — pupil-sparing), mononeuritis multiplex Prevention: tight glycaemic control reduces neuropathy risk by ~60% in T1DM (DCCT) and significantly in T2DM (UKPDS) Pain management (NICE CG173): first-line amitriptyline, duloxetine, gabapentin, or pregabalin; duloxetine 60-120 mg OD has best evidence for painful diabetic neuropathy Annual foot screening: 10g monofilament + clinical exam; NICE NG19

Overview

Key Facts

Diabetic neuropathy is the commonest microvascular complication of diabetes. Prevention through glycaemic control and early detection through screening are the most important interventions.

Epidemiology

~50% of diabetic patients have some neuropathy; ~25% have painful neuropathy. Risk increases with duration and poor control. Both T1DM and T2DM affected.

Aetiology

Hyperglycaemia is the primary driver. Other risk factors: dyslipidaemia, hypertension, smoking, obesity.

Pathophysiology

Polyol pathway (sorbitol accumulation), AGEs, PKC activation, oxidative stress, microvascular disease (vasa nervorum) → axonal degeneration and segmental demyelination.

Clinical Presentation

DSPN

  • Gradual onset; sensory > motor; glove-and-stocking
  • Numbness, tingling, burning pain (worse at night)
  • Absent ankle jerks, loss of monofilament sensation
  • Risk of painless injuries → neuropathic ulceration

Autonomic Neuropathy

  • CV: resting tachycardia, orthostatic hypotension, silent MI
  • GI: gastroparesis, constipation, diarrhoea
  • GU: erectile dysfunction, neurogenic bladder

Other Forms

  • Diabetic amyotrophy: painful proximal thigh weakness; self-limiting 12-18 months
  • CN III palsy: pupil-sparing (key distinction from compressive cause)

Red Flags

  • Loss of protective sensation → high amputation risk
  • Charcot foot (hot, swollen, painless joint destruction)

Differential Diagnosis

DiagnosisKey FeaturesInvestigation
B12 deficiencyMacrocytosis, glossitis (check — metformin causes B12 deficiency)B12 level
Alcohol-related neuropathyAlcohol excess, nutritional deficiencyHistory, LFTs
CIDPProximal + distal weakness, demyelinating NCSNCS, CSF
Hypothyroid neuropathyWeight gain, fatigueTFTs
Vasculitic neuropathyMononeuritis multiplex, systemic featuresESR, ANCA, biopsy

Diagnosis / Investigation

Bedside

  • 10g monofilament, vibration (128 Hz tuning fork), ankle reflexes

Bloods

  • HbA1c, B12 (metformin-induced deficiency), TFTs, SPEP, U&Es

Neurophysiology

  • NCS: axonal sensorimotor polyneuropathy (if diagnostic uncertainty)

Autonomic

  • Lying/standing BP, heart rate variability, gastric emptying study

Management

Prevention

  • Optimise glycaemic control: DCCT (~60% reduction T1DM), UKPDS (T2DM)
  • Cardiovascular risk management

Pain Management (NICE CG173)

  • First-line: amitriptyline 10-75 mg ON, duloxetine 60-120 mg OD, gabapentin 300-3600 mg/day, or pregabalin 150-600 mg/day
  • Combination therapy if monotherapy inadequate
  • Topical capsaicin 0.075% for localised pain
  • Pain clinic referral for refractory cases

Autonomic

  • Orthostatic hypotension: fludrocortisone, midodrine
  • Gastroparesis: domperidone 10mg TDS (short-term), dietary modification
  • Erectile dysfunction: PDE5 inhibitors

Foot Care (NICE NG19)

  • Annual risk assessment, podiatry, patient education

Prognosis

DSPN is slowly progressive. Tight glycaemic control slows but does not reverse established neuropathy. Diabetic foot ulceration: lifetime risk ~25%; 5-year mortality after amputation ~50%. Autonomic neuropathy with cardiac involvement: 5-year mortality ~25-50%.

Other Relevant Information

Types of Diabetic Neuropathy

TypeFeaturesPrognosis
DSPNSymmetric, sensory > motor, length-dependentChronic, progressive
Painful neuropathyBurning, nocturnalMay improve spontaneously
AutonomicCV, GI, GU dysfunctionIncreases mortality
Diabetic amyotrophyProximal, painful, thigh weaknessSelf-limiting
CN III palsyPupil-sparingSelf-limiting

Key Trials

TrialFinding
DCCTTight control in T1DM reduces neuropathy by ~60%
UKPDSTight control in T2DM reduces microvascular complications