Diabetic Autonomic Neuropathy Defined

Autonomic neuropathy affects the autonomic neurons of either or both of the parasympathetic and sympathetic nervous systems. They are usually accompanied by somatic neuropathy but can be autonomic only.

Autonomic testing should be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction.

Several syndromes and diseases exhibit autonomic neuropathies and there is a wide variety of clinical features and presentations.[2] In some patients the features are subclinical, whereas in others the dysfunction leads to significant disability.

It is important to recognise and correctly diagnose autonomic neuropathy because successful treatments and management can be offered.


As might be expected, various pathophysiological processes are involved depending on the particular cause. Although loss of somatic C fibres is associated with autonomic deficits, there is now known to be a more selective involvement of fibres in some conditions.

Somatic and autonomic C fibre involvement is found in diabetic neuropathies. The exact mechanism has not been worked out for all conditions and causes. However, the following have been identified and may be involved:

  • Single gene defects.
  • Accumulation of toxins.
  • Autoantibodies. For example:
  • Autonomic ganglionic acetylcholine receptor antibody (pandysautonomia).
  • Ganglionic receptor antibodies (postural orthostatic tachycardia syndrome).
  • Ganglioside autoantibodies (Guillain-Barré syndrome).
  • Antibodies to presynaptic channels (Eaton-Lambert syndrome).
  • Antineuronal antibodies (coeliac disease, paraneoplastic autonomic neuropathy).
  • Prevention of presynaptic acetylcholine release (botulism).
  • Accumulation of toxic metabolites (for example, in liver disease).
  • Postganglionic abnormalities (connective tissue diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis).
  • Accumulation of glycolipids (Anderson-Fabry disease).


There is a long list of causes including hereditary and acquired conditions. The full spectrum includes:

  • Ageing: postural hypotension and disordered thermoregulation are common in the elderly.
  • Causes linked with systemic diseases include:
  • Diabetic autonomic neuropathies[5]
  • Alcoholic neuropathy
  • Subacute combined degeneration
  • Liver disease
  • Chronic kidney disease
  • Amyloidosis
  • Infectious causes: eg, human immunodeficiency virus (HIV), Lyme disease, leprosy, Chagas’ disease.
  • Toxic causes: eg, vincristine, cisplatin, amiodarone, pyridoxine overdose, thallium poisoning, paclitaxel

Immune-mediated causes:

  • Rheumatoid arthritis, SLE, Sjögren’s syndrome, systemic sclerosis, autoimmune thyroiditis
  • Neuropathy related to inflammatory bowel disease
  • Postural orthostatic tachycardia syndrome (POTS)[6]
  • Guillain Barré syndrome
  • Chronic inflammatory demyelinating neuropathy
  • Acute pandysautonomia
  • Acute cholinergic pandysautonomia
  • Eaton-Lambert syndrome
  • Holmes-Adie syndrome
  • Paraneoplastic autonomic neuropathy
  • Hereditary causes: eg, Anderson-Fabry disease, Tangier disease, multiple endocrine neoplasia (type 2b).
  • Idiopathic causes: chronic idiopathic anhidrosis.


In general, these can occur in men and women at any age, but the epidemiology will depend on the particular cause. Some causes are very rare. However, one of the most common causes of autonomic neuropathy is likely to be diabetes mellitus.

Progressive autonomic failure usually becomes apparent in the sixth decade of life. Typically it manifests with genitourinary symptoms and orthostatic hypotension but without somatic symptoms.


Autonomic nervous system dysfunction may present with a variety of symptoms. Orthostatic intolerance (including orthostatic hypotension or tachycardia) and sweating abnormalities (increased or decreased sweating) are common problems.


Autonomic nerve fibres are affected in most symmetrical peripheral neuropathies; however, involvement is often subclinical or mild.[4] Usually the onset of symptoms is slow and insidious. Occasionally the onset can be acute and dramatic in the acute forms.

Usually there is sympathetic and parasympathetic dysfunction. Orthostatic or postural hypotension is the most commonly recognised symptom, but there is a wide variety of other possible symptoms. A family history and drug history may also be important.

Possible symptoms of autonomic neuropathy


  • There may be no sweating or reduced sweating (anhidrosis and hypohidrosis), but excessive sweating (or hyperhidrosis) can occur as a compensatory mechanism.
  • Temperature regulation
  • Hypothermia and hyperpyrexia can result from disruption of the various temperature regulatory mechanisms. Sweating, shivering and vasoactive reflexes can be affected
  • Reduced or absent sweating.


  • Blurring of vision.
  • Tunnel vision.
  • Light sensitivity.
  • Difficulty focusing.
  • Reduced lacrimation.
  • Gradual reduction of pupillary size.
  • Cardiovascular
  • Orthostatic hypotension (often associated with or exacerbated by eating, exercise and raised temperature).
  • Other orthostatic symptoms ( for example, nausea, palpitations, light-headedness, tinnitus, shortness of breath).
  • Syncope (may occur with micturition, defecation).
  • Inability to stand without syncope (severe cases).
  • Arrhythmias.
  • Supine hypertension.
  • Loss of diurnal variation in blood pressure (BP).
  • Respiratory

In those with diabetes, reduced bronchoconstrictor reflexes have been detected (contributing to reduced responses to hypoxia).


  • Constipation.
  • Diarrhoea.
  • Incontinence.
  • Dry mouth.
  • Disturbance of taste.


  • Impotence.
  • Ejaculatory failure.
  • Female sexual dysfunction.
  • Feet
  • Burning sensation.


  • Hair loss.
  • Pruritus.
  • Dry skin.
  • Pale, cold feet.
  • Worsening of symptoms at night.


There may be features on general examination which point to a specific disease. The neurological examination should be detailed and thorough, incorporating motor and sensory examination. There are a few specific techniques which can be used for certain specific autonomic abnormalities.[8]

General examination

  • Stigmata of liver disease.
  • Skin conditions (for example, Lyme disease and leprosy).
  • Signs of connective tissue diseases (for example, rheumatoid arthritis, SLE, Sjögren’s syndrome).
  • Features of unusual conditions (such as Anderson-Fabry disease and amyloidosis).
  • Neurological examination
  • Motor examination (power, tone, co-ordination and reflexes).
  • Sensory examination (all modalities including proprioception).


Management should start from initial diagnosis and incorporate patient education about the condition and implications for the patient. This may range from measures to prevent orthostatic hypotension to improvements in self-care (from hygiene to care of diabetes mellitus).

Treatment of the underlying cause.

There are a number of treatments for damage to nerves that control body systems. For example, a dietitian can help you plan meals if you have nausea or feel full after eating a small amount. Some medications can speed digestion and reduce diarrhea. Problems with erections can be treated with medications or devices. – See more at:

  • Orthostatic hypotension: see also the separate article on Hypotension.
  • Gastrointestinal dysfunction:
  • Gastroparesis in patients with diabetic autonomic neuropathy is improved by rigorous control of blood glucose. concentrations.
  • Eat small meals and eat often.
  • Lower the fat content of the diet.
  • Prokinetic agents for gastroparesis can be used (metoclopramide, domperidone and erythromycin). A jejunostomy tube may rarely be required.

Bowel hypomotility. This can be helped with:

  • Increased dietary fibre and an increase in fluid intake.
  • Use of stool softeners and/or an osmotic laxative.
  • Trying out a gluten-free diet and restriction of lactose.
  • Colestyramine, clonidine, somatostatin analogues, pancreatic enzyme supplements, and even antibiotics (such as metronidazole), which have been tried.
  • Genital autonomic neuropathy:
  • Treatment of erectile dysfunction.
  • Vaginal lubricants and oestrogen creams may help.
  • Autonomic dysfunction of the urinary tract:
  • Timed voiding schedules and bladder contractions increased by a Valsalva manoeuvre.
  • Clean intermittent self-catheterisation.
  • Cholinergic agonists (eg bethanechol) have a limited role).


Many complications exist. The most severe are:

  • Cardiac arrest, cardiac dysrhythmias, sudden cardiac death.
  • Blood pressure fluctuations and the risk of cerebral and cardiac ischaemia.


The prognosis is determined by the particular cause of the autonomic neuropathy. In most cases the course is one of gradual progression. In the case of diabetes mellitus the prognosis is improved with good control of diabetes.

Other measures to halt progression may be applicable, such as abstinence from alcohol or by treatment of correctable syndromes.

Source & More Info: Patient.co.uk and American Diabetes Association



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