Circadian rhythmicity of heart rate and QTc interval in diabetic autonomic neuropathy: Implications for the mechanism of sudden death

Abstract

Patients with diabetic autonomic neuropathy (DAN) exhibit decreased heart rate variability (HRV) and are prone to sudden death. When HRV was used as an index of DAN, the circadian rhythmicity of heart rate and QT intervals was studied in 17 patients with diabetes who had varying degrees of DAN and 13 healthy control subjects. Heart rate and QT and QTc intervals for all subjects were found to exhibit a significant circadian periodicity. Heart rate was lowest and QT and QTc intervals were longest between midnight and 6:00 am; heart rate increased and QT and QTc intervals shortened in the hours after waking. The diabetic group with more severe autonomic neuropathy (DAN+, HRV = 76 ± 20 msec, n = 7) had significantly higher heart rate and shorter QT and QTc intervals compared with the diabetic group without autonomic neuropathy (DAN−, HRV = 120 ± 13 msec, n = 10) or healthy control subjects (CT, HRV = 119 ± 26 msec, n = 13). Twenty-four-hour mean heart rate was 90 ± 7 beats/min (range, 79 to 98 beats/min) for DAN+, 77 ± 8 beats/min (range, 64 to 86 beats/min) for DAN− (DAN+ vs DAN−; p = 0.005), and 74 ± 7 beats/min (range, 64 to 80 beats/min) for CT (DAN+ vs CT; p = 0.0004). Mean 24-hour QTc was 391 ± 13 msec (range, 387 to 399) msec for DAN+, 417 ± 19 msec (range, 413 to 425 msec) for DAN− (DAN+ vs DAN−; p = 0.01), and 412 ± 28 msec (range, 408 to 419 msec) for CT (DAN+ vs CT; p = 0.09). These differences were significant according to analysis of variance and covariance with repeated measures. Reduced HRV, elevated heart rate, and abbreviated QTc intervals in patients with diabetes and severe autonomic neuropathy suggest sympathetic activation and/or parasympathetic denervation. These changes may be markers of autonomic imbalance that favor the development of ventricular arrhythmias and sudden death.