Table 5—

Diagnostic tests of CAN

  • Resting heart rate >100 bpm is abnormal.

  • Beat-to-beat HRV* With the patient at rest and supine (not having had coffee or a hypoglycemic episode the night before), heart rate is monitored by ECG or autonomic instrument while the patient breathes in and out at six breaths per minute, paced by a metronome or similar device. A difference in heart rate of >15 bpm is normal, <10 bpm is abnormal. The lowest normal value for the expiration-to-inspiration ratio of the R-R interval is 1.17 in people 20–24 years of age. There is a decline in the value with age.

  • Heart rate response to standing* During continuous ECG monitoring, the R-R interval is measured at beats 15 and 30 after standing. Normally, a tachycardia is followed by reflex bradycardia. The 30:15 ratio is >1.03.

  • Heart rate response to the Valsalva maneuver* The subject forcibly exhales into the mouthpiece of a manometer to 40 mmHg for 15 s during ECG monitoring. Healthy subjects develop tachycardia and peripheral vasoconstriction during strain and an overshoot bradycardia and rise in blood pressure with release. The ratio of longest R-R to shortest R-R should be >1.2.

  • Systolic blood pressure response to standing Systolic blood pressure is measured in the supine subject. The patient stands, and the systolic blood pressure is measured after 2 min. Normal response is a fall of <10 mmHg, borderline is a fall of 10–29 mmHg, and abnormal is a fall of >30 mmHg with symptoms.

  • Diastolic blood pressure response to isometric exercise The subject squeezes a handgrip dynamometer to establish a maximum. Grip is then squeezed at 30% maximum for 5 min. The normal response for diastolic blood pressure is a rise of >16 mmHg in the other arm.

  • ECG QT/QTc intervals The QTc should be <440 ms.

  • Spectral analysis Very-low-frequency peak↓ (sympathetic dysfunction) Low-frequency peak↓ (sympathetic dysfunction) High-frequency peak↓ (parasympathetic dysfunction) Low-frequency–to–high-frequency ratio↓ (sympathetic imbalance)

  • Neurovascular flow Using noninvasive laser Doppler measures of peripheral sympathetic responses to nociception.

  • From Vinik A, Erbas T, Pfeifer M, Feldman E, Stevens M, Russell J: Diabetic autonomic neuropathy, 2004. In The Diabetes Mellitus Manual: A Primary Care Companion to Ellenberg and Rifkin’s 6th Edition. Inzucchi SE, Ed. New York, McGraw Hill, 2004, p. 351.

  • *

    * These can now be performed quickly (<15 min) in the practitioner’s office using stand-alone devices that are operator friendly.

  • Lowest normal value of expiration-to-inspiration ratio: age 20–24 years, 1.17; 25–29, 1.15; 30–34, 1.13; 35–39, 1.12; 40–44, 1.10; 45–49, 1.08; 50–54, 1.07; 55–59, 1.06; 60–64, 1.04; 65–69, 1.03; and 70–75, 1.02. ECG, electrocardiogram.