What does screening for Diabetic Autonomic Neuropathy (DAN) involve?

Screening for Diabetic Autonomic Neuropathy (DAN)

Screen all patients with type 1 diabetes for ≥5 years and all patients with type 2 diabetes at diagnosis, then annually thereafter using cardiovascular autonomic reflex tests (CARTs) combined with symptom assessment and orthostatic blood pressure measurement. 1, 2

Who to Screen and When

• Type 1 diabetes: Begin screening after 5 years of disease duration 1, 2
• Type 2 diabetes: Screen at diagnosis and annually thereafter 1, 2
• High-priority patients: Those over age 50, hypertensive diabetics, and patients with other diabetic complications warrant particular attention for yearly orthostatic hypotension testing 3

Initial Symptom Assessment

Ask specifically about the following symptoms during every screening encounter 1, 2:

• Cardiovascular: Orthostatic intolerance (lightheadedness upon standing), syncope or near-syncope episodes, exercise intolerance, unexplained tachycardia 1, 2
• Gastrointestinal: Gastroparesis symptoms (early satiety, nausea, vomiting), constipation, diarrhea 1, 2
• Genitourinary: Bladder dysfunction, erectile dysfunction, urinary symptoms 1, 2
• Sudomotor: Sweating abnormalities (anhidrosis, heat intolerance, dry skin, hyperhidrosis) 3, 1

Gold Standard Testing: Cardiovascular Autonomic Reflex Tests (CARTs)

CARTs are the gold standard for DAN diagnosis and must include multiple tests, not just one. 3, 2 The battery consists of:

Heart Rate Tests (Parasympathetic Function)

• Heart rate variability with deep breathing (most sensitive early test) 3, 2
• Heart rate response to standing (lying-to-standing test) 3
• Heart rate response to Valsalva maneuver 3

Blood Pressure Tests (Sympathetic Function)

• Orthostatic hypotension test: Measure blood pressure supine and after standing 3
  • Defined as ≥20 mmHg drop in systolic or ≥10 mmHg drop in diastolic blood pressure 3
  • This test should be performed yearly regardless of symptoms, especially in patients >50 years and hypertensive diabetics 3

Testing Conditions and Standardization

To ensure accurate results, strictly control these factors 3, 2:

• Environment: Quiet room, temperature 21-23°C 2
• Fasting: 3 hours before testing, at least 2 hours after light meal 3, 2
• Avoid: Caffeine, alcohol, smoking for ≥2 hours prior; strenuous exercise for 24 hours prior 3, 2
• Timing: Avoid testing during hypoglycemia, marked hyperglycemia, acute illness, fever, infection, or dehydration 3, 2
• Medications: Ideally wash out interfering drugs (diuretics, sympatholytics, psychoactive drugs); if not feasible, interpret with caution 3
• Insulin: Perform at least 2 hours after short-acting insulin administration 3

Diagnostic Criteria and Staging

Use age-adjusted normal reference values for all heart rate tests 3 and apply the following diagnostic criteria:

• Early/Possible CAN: One abnormal heart rate test result 3, 2
• Definite/Confirmed CAN: Two or more abnormal heart rate test results 3, 2
• Severe/Advanced CAN: Orthostatic hypotension plus abnormal heart rate tests 3, 2

Additional Screening Tests (When Indicated)

Cardiac Screening

• Resting heart rate: Unexplained tachycardia (>100 bpm) warrants full CAN testing 3
• QTc interval: Prolongation suggests CAN but is insufficient alone; should prompt further testing 3
• 24-hour ambulatory blood pressure monitoring (ABPM): Not routinely recommended for diagnosis, but reverse dipping pattern (95% specific, 25% sensitive) should prompt CAN testing 3

Gastrointestinal Screening

• Gastric emptying scintigraphy (4-hour test): Gold standard for gastroparesis 2
• Electrogastrography: Alternative screening tool 3

Genitourinary Screening

• Bladder ultrasound: Assess residual urine volume for bladder dysfunction 3

Critical Pitfalls to Avoid

• Never rely on a single test: DAN diagnosis requires a battery of tests, not one abnormal result 3, 2
• Never ignore age: Failure to use age-adjusted normal values leads to misdiagnosis 3
• Never test during glycemic instability: Hypoglycemia or marked hyperglycemia invalidates results 3, 2
• Never overlook confounders: Resting heart rate >100 bpm, supine systolic BP >160 or <120 mmHg, respiratory/cardiovascular disease, and medications all affect interpretation 3
• Never skip orthostatic testing: Even asymptomatic patients require yearly orthostatic blood pressure measurement, especially those >50 years 3
• Never perform Valsalva with proliferative retinopathy: Risk of retinal hemorrhage 3

Clinical Utility of Screening

Early detection through systematic screening allows for 3:

• Risk stratification for cardiovascular mortality, silent myocardial ischemia, sudden death, and nephropathy progression 3
• Identification of patients requiring careful perioperative hemodynamic monitoring 3
• Tailored exercise prescriptions using perceived exertion rather than heart rate targets 3
• Avoidance of QT-prolonging drugs and drugs with adverse autonomic effects 3
• Adjustment of antihypertensive therapy to account for orthostatic changes 3