There are separate articles Managing Diabetes in General Practice and Diabetic Foot.

Diabetic neuropathy is a common complication of both type 1 diabetes and type 2 diabetes. Neuropathy plays a major role in the development of foot ulcers, which cause an enormous effect on quality of life for the patient (especially if amputation becomes necessary) and is also responsible for a very large health and social services expenditure.

Optimal control of all metabolic factors and regular organised surveillance of all people with diabetes is essential to reduce the risk of both development and progression of diabetic neuropathy and therefore reduce the risk of disability for the patient.

Motor, sensory and autonomic fibres may all be affected by diabetic neuropathy.

Epidemiology¹

20-30% of individuals with type 2 diabetes develop neuropathy. Type 1 diabetics usually develop neuropathy after more than 10 years of living with the disease.

Risk factors

• Smoking
• Aged over 40 years
• History of periods of poor glycaemic control
• Prevalence increases with increased duration of diabetes
• People with signs of neuropathy are likely also to have evidence of diabetic nephropathy and diabetic retinopathy
• Hypertension
• Ischaemic heart disease

Presentation^1,2,3

This depends on the type of neuropathy involved. Early features of neuropathy often go unrecognised by the patient, further emphasising the importance of routine surveillance.

Peripheral sensorimotor (chronic peripheral neuropathy)

• Sensory nerves are affected more than motor.
• Touch, pain and temperature sensation and proprioception in lower limbs in a glove and stocking distribution.
• Loss of ankle jerks and, later, knee jerks.
• Hands are only affected in severe longstanding neuropathy.
• Equal prevalence in types 1 and 2.

Acute diffuse painful (acute peripheral neuritis)

• Often abrupt onset and not related to duration of diabetes.
• Can resolve completely.
• Burning foot pain, often worse at night.
• Associated with poor glycaemic control but sometimes initially follows establishing good glycaemic control.
• Examination may be normal apart from hyperaesthesia.

Autonomic neuropathy

• Risk factors include hypertension and dyslipidaemia. It is more common in females
• May present with:
  • Genitourinary:
    • Impotence, retrograde ejaculation, urinary hesitancy, overflow incontinence
    • At least 25% of male diabetics have problems with sexual function
    • There is often no association with glycaemic control, duration or severity of diabetes
    • Risk factors for erectile dysfunction include increasing age, alcohol, initial glycaemic control, intermittent claudication and retinopathy
  • Gastrointestinal: nausea and vomiting, abdominal distension, dysphagia, diarrhoea
  • Gustatory sweating, anhidrosis
  • Dizziness due to postural hypotension
• Tends to be associated with peripheral neuropathy
• People with both types 1 and 2 are affected
• High mortality rate (50% within 3 years) mainly due to renal failure but often no obvious cause
• Tight glycaemic control reduces the risk

Mononeuropathy

• External pressure or entrapment, e.g. carpal tunnel syndrome.
• Isolated neuropathies of either the cranial or peripheral nerves. Mononeuropathies of cranial nerves III, IV and VI, intercostal nerves and femoral nerves are common.
• Occasionally more than one nerve is involved (mononeuritis multiplex).

Proximal motor (diabetic amyotrophy)

• Main motor manifestation.
• Severe pain and paraesthesiae in the upper legs, with weakness and muscle wasting of the thigh and pelvic girdle muscles.
• May be asymmetrical and there may be extensor plantars.
• Mainly affects middle-aged and elderly patients.
• Usually associated with a period of very poor glycaemic control, sometimes with dramatic weight loss.
• Pain and weakness gradually reduce once good glycaemic control has returned.

Differential diagnosis

• Other possible causes of neuropathy include:
• Toxins, e.g. alcohol, occupational, vitamin B6, medications (e.g. amiodarone)
• Hypothyroidism
• Pernicious anaemia
• Malignancies, amyloidosis
• Collagen vascular disease, neurosarcoidosis
• Tabes dorsalis, AIDs
• Spinal cord disease, cauda equina syndrome

Investigations

• Full assessment of diabetes and blood pressure control. Assessment of other possible causes, e.g. thyroid function tests, B12.
• May require nerve conduction studies and electromyography.

Management⁴

• Regular surveillance for signs of neuropathy to allow early intervention.
• Tight glycaemic control.
• Prevention of foot trauma.

Management of painful neuropathy

• May require a great deal of support for the depressing and disabling nature of the condition
• General measures
  • Bed foot cradles for night-time problems
  • Simple analgesia taken in advance of diurnal symptoms
  • Contact dressings
• Drug treatments recommended by the National Institute for Health and Clinical Excellence (NICE)
  • Oral duloxetine should be offered first-line. Starting dose 60 mg/day (may need lower in the elderly or comorbidities affecting metabolism); maximum 120 mg/day.
  • Offer oral amitriptyline (10-75 mg/day) if duloxetine is contra-indicated (e.g. severe narrow-angle glaucoma, previous hypersensitivity reaction).
  • Amitriptyline can also be used as a second-line drug if duloxetine does not work. Pregabalin (150-600 mg/day in 2 divided doses) can also be tried, either alone or in combination with amitriptyline.
  • If second-line treatment fails consider referral (see 'When to refer' section below). In the interim, try tramadol (50-100 mg no more than 4-hourly; maximum 400 mg daily as monotherapy, and may need lower doses if combined with other drugs).
  • Topical lidocaine gel can be prescribed whilst awaiting specialist appointment for patients with localised pain who cannot take oral drugs due to comorbidity or disability.
  • Opioids other than tramadol should be avoided unless part of shared-care arrangements after specialist assessment.
  • Patients on drug treatment should be reviewed early when starting treatment for dosage titration, or when changing dose to monitor for adverse effects and tolerability.
  • Regular reviews (NICE does not specify time interval) should also be arranged to check progress, adverse effects, mood, quality of sleep and any problems with daily activities.

When to refer

Consider referral to a pain clinic and/or condition-specific service at any stage (including initial presentation) if:

• Pain is severe
• Pain significantly limits activity
• The underlying condition has deteriorated

Management of autonomic neuropathy^3,5

See separate article Autonomic Neuropathy. In all patients, optimise diabetic control.

• Cardiovascular effects - various cardioactive drugs are being used to reverse the effects on the cardiovascular system, including angiotensin-converting enzyme (ACE) inhibitors, betablockers, diuretics and digoxin
• Erectile dysfunction: see separate article Erectile Dysfunction
• Gastroparesis
  • Investigation using radiological or radioisotope methods may help in the diagnosis
  • Investigation of cardiovascular autonomic neuropathy may help in the diagnosis
  • Metoclopramide and domperidone are worth a trial
• Diabetic nocturnal diarrhoea
  • Investigation must exclude other causes of intestinal upset
  • May be helped by high doses of codeine, loperamide or diphenoxylate, or by erythromycin or tetracycline
• Gustatory sweating
  • Explanation and counselling are often required
  • Topical or oral anticholinergic agents (e.g. poldine methylsulfate) may be effective
• Postural hypotension
  • May respond to fludrocortisone

Prognosis^5,6

• Autonomic neuropathy is associated with a high mortality rate, mainly due to its association with renal failure, cardiopathy and hypotension.
• Diabetics are more likely to undergo lower limb amputation than nondiabetics.

Prevention

• Tight glycaemic control has been clearly shown to reduce the risk of neuropathy.
• Smoking avoidance or cessation.

Document references

1. Sherman A, Echeverry D; Diabetic Neuropathy, eMedicine, Oct 2009.
2. Guidelines on the management of neuropathic pain; Clinical Resource Efficiency Support Team (February 2008).
3. Quan D; Diabetic Neuropathy, eMedicine, Oct 2009.
4. Neuropathic pain - pharmacological management, NICE Clinical Guideline (March 2010); The pharmacological management of neuropathic pain in adults in non-specialist settings
5. Vinik AI, Ziegler D; Diabetic cardiovascular autonomic neuropathy. Circulation. 2007 Jan 23;115(3):387-97.
6. Management of diabetes, Scottish Intercollegiate Guidelines Network (SIGN), March 2010

Internet and further reading

• Diabetes guidelines, NICE; various dates
• Diabetes UK

Acknowledgements