Complexity of Impaired Parasympathetic Heart Rate Regulation in Diabetes

  1. Jens Tank
  1. Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany
  1. Corresponding author: Jens Jordan, jordan.jens{at}

The autonomic nervous system is crucial for blood pressure and heart rate regulation. Sympathetic efferent fibers elicit vasoconstriction, raise heart rate and cardiac contractility, and promote sodium reabsorption through direct renal tubular actions and renin-angiotensin system activation. Parasympathetic efferent fibers rapidly reduce heart rate. Both autonomic branches are tightly controlled by baroreflex, stabilizing blood pressure in a feedback fashion (1). Severe autonomic failure due to sympathetic and parasympathetic dysfunction typically occurs in patients with long-standing and poorly controlled diabetes. The condition is associated with profound orthostatic hypotension, postprandial hypotension, a fixed heart rate, and exercise intolerance. Positron emission tomography or single photon emission tomography imaging with tracers taken up by adrenergic sympathetic nerve endings suggest that autonomic efferent nerves are irreversibly damaged in these patients (2,3). There are no causative treatments for late-stage disease and symptomatic treatment is difficult. Clinicians caring for autonomic failure patients are faced with the therapeutic dilemma that blood pressure is often markedly elevated in the supine position (4). Yet, antihypertensive treatment exacerbates orthostatic hypotension. Conversely, treatment of orthostatic hypotension with pressor agents might hasten cardiovascular and renal disease progression. The condition carries a poor prognosis.

More subtle changes in cardiovascular autonomic regulation are common early in the course of type 1 or type 2 diabetes. Typically, impaired parasympathetic heart rate control precedes sympathetic dysfunction. Simple bedside tests, such as respiratory sinus arrhythmia assessment during deep breathing, are often diagnostic (5). Heart rate variability and noninvasive baroreflex sensitivity measurements are also useful diagnostic tools, particularly in epidemiologic …

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