What is the approach to testing for autonomic neuropathy?

Testing for Autonomic Neuropathy

A comprehensive approach to testing for autonomic neuropathy should include a battery of validated tests rather than a single test to achieve the highest diagnostic accuracy, with cardiovascular autonomic testing being the most standardized and widely available method. 1, 2

Initial Assessment

• Screening for autonomic neuropathy should be performed in individuals who have had type 1 diabetes for ≥5 years and in all individuals with type 2 diabetes at diagnosis, with annual assessments thereafter 1
• Symptoms to specifically inquire about include:
  • Orthostatic intolerance (dizziness, lightheadedness, weakness when standing) 1, 2
  • Syncope or near-syncope episodes 1
  • Exercise intolerance 1
  • Gastrointestinal symptoms (constipation, diarrhea, early satiety, nausea) 1, 3
  • Urinary symptoms (retention, incontinence) 1
  • Sexual dysfunction (erectile dysfunction in men, decreased arousal/lubrication in women) 1, 3
  • Sweating abnormalities (hyperhidrosis or anhidrosis) 1, 2

Cardiovascular Autonomic Testing

• Cardiovascular autonomic reflex tests (CARTs) are the gold standard for clinical diagnosis of autonomic neuropathy 1

• The recommended battery of tests includes:

  1. Heart rate variability (HRV) testing - measures response to deep breathing, standing, and Valsalva maneuver 1
  2. Baroreflex sensitivity testing 1
  3. Orthostatic hypotension assessment - blood pressure response to standing or tilt 1

• Diagnostic criteria for cardiovascular autonomic neuropathy (CAN):

  • Early CAN: One abnormal heart rate test result 1
  • Definite CAN: Two or more abnormal heart rate test results 1
  • Severe CAN: Presence of orthostatic hypotension along with abnormal heart rate tests 1

Gastrointestinal Autonomic Testing

• For suspected gastroparesis:
  • Gastric emptying scintigraphy (4-hour test) is the diagnostic gold standard 1
  • 13C octanoic acid breath test is an approved alternative 1
• Prior to specialized testing, exclude reversible/iatrogenic causes:
  • Medication effects 1
  • Organic causes of gastric outlet obstruction 1
  • Peptic ulcer disease (via endoscopy or barium study) 1

Sudomotor Function Testing

• Quantitative sudomotor axon reflex testing can assess sweat gland function 4
• Particularly useful for small fiber neuropathy evaluation 1, 3

Genitourinary Testing

• For bladder dysfunction:
  • Ultrasound to determine bladder volume and residual urine 1
  • Urodynamic studies for more detailed assessment 1
• For erectile dysfunction:
  • Nocturnal penile tumescence testing 5
  • Tests to assess penile, pelvic, and spinal nerve function 5

Testing Conditions and Precautions

• Testing should be performed in a quiet environment with controlled temperature (21-23°C) 6

• Patient preparation:

  • Fast for 3 hours before testing 6
  • Avoid caffeine, alcohol, and smoking for at least 2 hours prior 1
  • Avoid strenuous physical exercise for 24 hours before testing 1
  • Testing should be performed at least 2 hours after a light meal 1
  • If on insulin, testing should be at least 2 hours after short-acting insulin administration 1

• Avoid testing during:

  • Acute illness, fever, infection, or dehydration 1, 6
  • Hypoglycemia or marked hyperglycemia 1

Interpretation and Staging

• Age-related normal reference values are required for accurate interpretation 1
• Consider confounding factors:
  • Medications (particularly diuretics, sympatholytic agents, and psychoactive drugs) 1
  • Respiratory or cardiovascular diseases 1
  • Resting heart rate >100 bpm may affect heart rate test interpretation 1
  • Supine systolic blood pressure >160 mmHg or <120 mmHg may affect orthostatic testing 1

Common Pitfalls to Avoid

• Relying on a single test rather than a battery of validated tests 1
• Failing to consider age-related changes in autonomic function 1
• Not controlling for medications that can affect autonomic function 1, 6
• Testing during periods of glycemic instability 1
• Overlooking autonomic neuropathy in patients with small fiber neuropathy 1, 2, 3