Autonomic Cardiac Regulation During Spontaneous, Nocturnal Hypoglycemia in Patients With Type 1 Diabetes

  1. Heikki V. Huikuri, MD 1
  1. 1Department of Internal Medicine, University of Oulu, Oulu, Finland
  2. 2Department of Clinical Neurophysiology, University of Oulu, Oulu, Finland
  3. 3Department of Exercise and Medical Physiology, Verve Research, Oulu, Finland
  4. 4Department of Internal Medicine, University of Turku, Turku, Finland
  1. Corresponding author: Minna L. Koivikko, minna.koivikko{at}


OBJECTIVE Experimental clamp studies have suggested that hypoglycemia evokes a reduction of cardiac vagal control in patients with type 1 diabetes. However, there are limited data on the influence of spontaneous nocturnal hypoglycemia on cardiac autonomic regulation.

RESEARCH DESIGN AND METHODS Adults with type 1 diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous sensor as well as recording of R-R interval or electrocardiogram for 3 nights. Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose<3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period (glucose >3.9 mmol/L) of equal duration and at the same time of night.

RESULTS The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190 min (mean 71 min). HR (62 ± 7 vs. 63 ± 9 beats per min; P = 0.30) or the high-frequency component of HR power spectrum (2,002 ± 1,965 vs. 1,336 ± 1,506 ms2; P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a significant decrease in the low-frequency component of HR variability (2,134 ± 1,635 vs. 1,169 ± 1,029 ms2, respectively; P = 0.006). The decline in the glucose concentration displayed a significant positive correlation with the decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04). The latter was closely related to an increase in muscle sympathetic nerve activity recorded in 10 subjects during controlled sympathetic activation.

CONCLUSIONS Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes results in a reduction of the low-frequency component of HR, which is best explained by excessive sympathetic activation without a concomitant withdrawal of vagal outflow.

  • Received October 31, 2011.
  • Accepted March 1, 2012.

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