Dead in bed syndrome was first described by Tattersal et al in 1991. In that study, 20 patients with type 1 diabetes who had died suddenly in the United Kingdom in 1989 were identified. All had appeared healthy on the day before death, and all had been found “dead in bed” in the morning without the bed being disturbed. Subsequently, studies from other countries have confirmed a low but significant incidence of dead in bed syndrome.

Stay connected - Sign Up for the E-mail News Wire!

It has always been assumed, though never proven, that dead in bed syndrome is due to a cardiac arrhythmia induced by nocturnal hypoglycemia. Recent studies have shown that hypoglycemia prolongs the QT interval, which could precipitate ventricular arrhythmias.

The QT interval starts with ventricular depolarization (Q wave) and ends with ventricular repolarization (the end of the T wave). Since the QT interval is longer during bradycardia and shorter during tachycardia, it is standardized by the Bazzett formula to the corrected QT interval (QTc). Prolongation of the QTc occurs with genetic or acquired abnormalities such as those associated with the use of antipsychotic medications and results in a specific ventricular arrhythmia such as torsades-de-pointes, an arrhythmia which often precedes ventricular fibrillation. Torsades-de-pointes does not occur with a QTc of below 500 milliseconds and is unlikely to be associated with a fatal arrhythmia in the absence of underlying cardiac pathology.

Therefore, the mystery of the dead in bed syndrome is why, in the absence of cardiac pathology, do hypoglycemia-induced arrhythmias occur. One possibility is cardiac denervation associated with diabetic autonomic neuropathy. In the early stages of autonomic neuropathy there is selective cardiac vagal denervation with disproportionate sympathetic activity that can lead to cardiac arrhythmias and sudden death if a prolonged QTc is present. Beta-blockers decrease the QTc and have been associated with a decrease in sudden death in the patients with diabetes who has sustained a myocardial infarction. However, during experimentally induced hypoglycemia in patients with cardiac denervation due to diabetic autonomic neuropathy, the QTc does not increase so that paradoxically these patients may be protected from sudden death by the presence of cardiac denervation.

Therefore, the situation in which hypoglycemia-induced prolongation of the QTc and a ventricular arrhythmia is most likely to occur is in a young person with a short duration of diabetes who is able to mount a robust sympathetic response to hypoglycemia. However, in the absence of significant cardiac pathology this robust sympathetic response is unlikely to cause a ventricular arrhythmia or sudden death.

What then is the underlying cardiac pathology of dead in bed syndrome?

It is my belief that the underlying cardiac pathology is the presence of a mitral valve prolapse. Anatomically in most situations the presence of mitral valve prolapse is of little or no significance. However, it is in many situations associated with cardiac dysautonomia, which is caused by sympathetic and/or parasympathetic overactivity and when a prolonged QTc is present there is a higher risk of a ventricular arrhythmias and sudden death. The prevalence of mitral valve prolapse has been shown to be increased in endocrine autoimmune diseases such as Graves disease, Hashimoto’s thyroiditis and type 1 (but not type 2) diabetes.

Therefore, it is my hypothesis that dead in bed syndrome occurs as a result of a ventricular arrhythmia caused by an increased QTc, which in turn is due to hypoglycemia-induced sympathetic overactivity in a predisposed young patient with type 1 diabetes and that these patients are predisposed to prolonged QTc and ventricular arrhythmias because of an underlying cardiac dysautonomia associated with mitral valve prolapse.

For more information:

• Bell DS, Acton RT. Increased prevalence of mitral valve prolapse in IDDM. Diabetes Care. 1996;19:672.
• Bell DS. Dead in bed syndrome - a hypothesis. Diabetes Obes Metab. 2006;8:261-263.
• Lee SP, Yeoh L, Harris ND, et al. Influence of autonomic neuropathy on QTc interval lengthening during hypoglycemia in type 1 diabetes. Diabetes. 2004;53:1535-1542.
• Tattersall RB, Gill GV. Unexplained deaths of type 1 diabetic patients. Diabet Med. 1991;8:49-58.

David S. H. Bell, MB, FACE, is a Clinical Professor of Medicine at the University of Alabama School of Medicine, Birmingham, and is an Endocrine Today Editorial Board member.