Sudden death in type 1 diabetes: The mystery of the ‘dead in bed’ syndrome Emily Tu a,b , Stephen M. Twigg b,c , Christopher Semsarian a,b,d, ⁎ a Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia b Central Clinical School, Faculty of Medicine, University of Sydney, Australia c Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia d Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Received 26 May 2008; accepted 3 June 2008 Available online 3 August 2008 Abstract Sudden cardiac death is an unpredictable and devastating event, particularly in the young. A significant proportion of sudden deaths in the young are unexplained—no cause is identified either during life or at post-mortem. This is seen in a subgroup of young patients with type 1 diabetes who have dead in bed syndrome, where these victims are in good health, retire to bed, only to be found dead the following morning in a bed which is undisturbed, suggesting no terminal struggle or seizure. The underlying cause of dead in bed syndrome remains unknown, but is likely to be due to a terminal malignant arrhythmia. A plausible hypothesis is that it may be secondary to QT interval prolongation (followed by a degenerate ventricular tachycardia), caused by a number of factors including acute hypoglycaemia, on a background of cardiac autonomic neuropathy, and possible genetic influences. It is envisaged that understanding the causes and triggers of dead in bed syndrome will allow appropriate therapeutic interventions to be initiated in high-risk patients with type 1 diabetes, with the ultimate goal to prevent sudden death. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Type 1 diabetes; Dead-in-bed; Sudden death; Genes ⁎ Corresponding author. Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Locked Bag No. 6, Newtown, NSW, 2042, Australia. Tel.: +61 2 9565 6195; fax: +61 2 9565 6101. E-mail address: c.semsarian@centenary.org.au (C. Semsarian). 1. Sudden cardiac death in the young Sudden death in the young is a devastating and unpredictable complication of a number of cardiovascular diseases. While underlying coronary artery disease is the major cause of sudden cardiac death in older populations, many other aetiologies contribute to this problem in those aged less than 35 years. In particular sudden cardiac death in the young can be caused by a number of inherited disorders which can affect both the structure of the heart (e.g. hypertrophic cardiomyopathy) or the conduction system (e.g. familial long QT syndrome) [1]. Unfortunately, the cause of sudden death in the young may not be known either during life, or even at post-mortem. Specifically, the heart at post-mortem may appear comple- tely normal both on macroscopic and histology analysis, and no other cause of death identified. In these cases the cause of death is often classified as “unascertained”, or “negative autopsy”, that is, no identifiable cause of death is found at post-mortem. A recent review of autopsies in Sydney, Australia between 1994 and 2002, identified 31% of young people who died suddenly from a presumed cardiac event had a negative autopsy [2]. Sudden deaths that remain unexplained after autopsy are most likely caused by electrical/arrhythmogenic disorders of the heart. Arrhythmo- genic disorders such as long QT syndrome, idiopathic ventricular fibrillation, and Brugada syndrome leave no evidence of pathological abnormalities of the heart at post- mortem. These arrhythmogenic disorders, all of which predispose individuals to primary cardiac arrhythmias and sudden death, are identified in up to 40% of negative autopsy sudden deaths. Of particular interest is a subgroup of unexplained deaths in young patients with type 1 diabetes. 2. Sudden death in type 1 diabetes: the “dead in bed syndrome” Cardiovascular complications in both type 1 and type 2 diabetes remain a major cause of morbidity and mortality, with both incidence and prevalence continuing to increase world-wide [3]. Mortality in young patients with type 1 diabetes is broadly categorized into two groups; deaths directly related to diabetes, such as acute complications of 91 Letters to the Editor