The mechanism of dead-in-bed syndrome and other sudden unexplained nocturnal deaths


Abstract

The mechanism of dead-in-bed syndrome (DBS), a rare but devastating condition that mainly affects young type 1 diabetes patients, remains mysterious. A new theory is proposed to explain this syndrome. This theory suggests that repeated episodes of hypoglycaemia-induced adaptation in orexin-A neurons cause (i) defective awakening and (ii) hypotonia of upper airway muscles during sleep. Consequently, due to the combined effect of these factors, long-term exposure of intermittent hypoxia occurs, leading to a combination of factors – such as depression of ventilation, increase in sympathetic tone, fluctuations in intrathoracic pressure and cardiac arrhythmias – these in conjunction with an underlying cardiovascular pathology (genetically inherited or acquired) cause cardio-respiratory failure and thus sudden death during sleep. This mechanism can be generalized to explain other cases of sudden unexplained nocturnal deaths including sudden infant deaths (SIDs).

 Orexin and sleep patterns

One group of researchers called these chemicals orexins and another, independent group of called themhypocretins.  Both names are used in the scientific literature. We prefer Orexin because it is shorter.

Orexins play a part in keeping people awake.  Like most of what goes on in the brain related to sleep and waking, there are mysteries and anyone who says they really understand every role that the orexin neurotransmitters play is lying.  But we know they are peptides – smallish proteins made in the body.  They also interact with other neurotransmitters in ways yet to be untangled, but they unquestionably appear to be involved in arousal and excitation of the brain.  The evidence suggests they form a part of the body’s overall sleep-wake regulation system by interacting with GABAergic sleep-promoting neurons and neurotransmitters like histamine, serotonin, melatonin, and acetylcholine. (More here: http://www.ncbi.nlm.nih.gov/pubmed/21170610)

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A potential role for adjunctive vitamin D therapy

Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects.