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Post-mortem pathologic and genetic studies in "dead in bed syndrome" cases in type 1 diabetes mellitus

Hum Pathol. 2010 Mar;41(3):392-400. doi: 10.1016/j.humpath.2009.08.020. Epub 2009 Dec 11.

Abstract

Dead in bed syndrome is a poorly understood cause of sudden death in young people with type 1 diabetes. The underlying cause remains unknown. One possible explanation may involve prolongation of the QT interval followed by a terminal malignant arrhythmia. Risk factors associated with QT interval prolongation include hypoglycemia and cardiac autonomic neuropathy. We sought to identify myocardial cellular changes and genetic influences that may contribute to the pathogenesis of dead in bed syndrome. Post-mortem reports between 1994 and 2006 from the 2 largest Departments of Forensic Medicine in Australia were reviewed for dead in bed syndrome cases. Post-mortem heart sections were immunohistochemically stained for collagen types I and III and connective tissue growth factor (CTGF). Genomic DNA was prepared from post-mortem samples, and genetic analysis was performed in the SCN5A, G6PC, PHOX2B, and CTGF genes. Twenty-two dead in bed syndrome cases were identified and staining of heart sections for collagen I and III, and CTGF showed no differences between dead in bed syndrome cases and controls. Genetic screening of SCN5A revealed 3 silent polymorphisms A29A, E1061E, and D1819D and 1 protein-changing variant H558R. No genetic variants were found in G6PC, PHOX2B, and CTGF, and dead in bed syndrome cases were not associated with the G-945C CTGF promoter polymorphism. In conclusion, this study is the first to investigate potential pathogenic mechanisms underlying the dead in bed syndrome in type 1 diabetes with the results substantially adding to knowledge of this condition. Understanding the causes and triggers of dead in bed syndrome will be critical in facilitating the identification of patients with type 1 diabetes at highest risk of developing sudden death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Australia
  • Chi-Square Distribution
  • Collagen Type I / metabolism
  • Collagen Type III / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Death, Sudden / etiology
  • Death, Sudden / pathology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Genetic Predisposition to Disease
  • Glucose-6-Phosphatase / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Hypoglycemia / genetics
  • Hypoglycemia / metabolism
  • Hypoglycemia / pathology
  • Immunohistochemistry
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Polymorphism, Genetic / genetics
  • Retrospective Studies
  • Risk Factors
  • Sequence Analysis, DNA
  • Sodium Channels / genetics
  • Transcription Factors / genetics

Substances

  • Collagen Type I
  • Collagen Type III
  • Homeodomain Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • NBPhox protein
  • SCN5A protein, human
  • Sodium Channels
  • Transcription Factors
  • Connective Tissue Growth Factor
  • Glucose-6-Phosphatase
  • G6PC2 protein, human