Environmental determinants of islet autoimmunity (ENDIA): A pregnancy to early life cohort study in children at-risk of type 1 diabetes

Megan A S Penno, Jennifer J. Couper, Maria E. Craig, Peter G. Colman, William D. Rawlinson, Andrew M. Cotterill, Timothy W. Jones, Leonard C. Harrison, Peter A. Baghurst, Simon C. Barry, Fergus J. Cameron, Jodie M. Dodd, Chris Duran, Josephine M. Forbes, Maria Makrides, Grant Morahan, Karen E. Nelson, Alison J. Nankervis, Richard O. Sinnott, John M. Wentworth

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27 Citations (Scopus)

Abstract

Background: The incidence of type 1 diabetes has increased worldwide, particularly in younger children and those with lower genetic susceptibility. These observations suggest factors in the modern environment promote pancreatic islet autoimmunity and destruction of insulin-producing beta cells. The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is investigating candidate environmental exposures and gene-environment interactions that may contribute to the development of islet autoimmunity and type 1 diabetes.Methods/design: ENDIA is the only prospective pregnancy/birth cohort study in the Southern Hemisphere investigating the determinants of type 1 diabetes in at-risk children. The study will recruit 1,400 unborn infants or infants less than six months of age with a first-degree relative (i.e. mother, father or sibling) with type 1 diabetes, across five Australian states. Pregnant mothers/infants will be followed prospectively from early pregnancy through childhood to investigate relationships between genotype, the development of islet autoimmunity (and subsequently type 1 diabetes), and prenatal and postnatal environmental factors. ENDIA will evaluate the microbiome, nutrition, bodyweight/composition, metabolome-lipidome, insulin resistance, innate and adaptive immune function and viral infections. A systems biology approach will be used to integrate these data. Investigation will be by 3-monthly assessments of the mother during pregnancy, then 3-monthly assessments of the child until 24 months of age and 6-monthly thereafter. The primary outcome measure is persistent islet autoimmunity, defined as the presence of autoantibodies to one or more islet autoantigens on consecutive tests.Discussion: Defining gene-environment interactions that initiate and/or promote destruction of the insulin-producing beta cells in early life will inform approaches to primary prevention of type 1 diabetes. The strength of ENDIA is the prospective, comprehensive and frequent systems-wide profiling from early pregnancy through to early childhood, to capture dynamic environmental exposures that may shape the development of islet autoimmunity.Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12613000794707.

Original languageEnglish
Article number124
JournalBMC Pediatrics
Volume13
Issue number1
DOIs
Publication statusPublished - 14 Aug 2013

Keywords

  • Beta cell
  • Immunity
  • Infancy
  • Insulin resistance
  • Islet autoimmunity
  • Microbiome
  • Pregnancy
  • Systems biology
  • Type 1 diabetes
  • Virus

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Penno, M. A. S., Couper, J. J., Craig, M. E., Colman, P. G., Rawlinson, W. D., Cotterill, A. M., ... Wentworth, J. M. (2013). Environmental determinants of islet autoimmunity (ENDIA): A pregnancy to early life cohort study in children at-risk of type 1 diabetes. BMC Pediatrics, 13(1), [124]. https://doi.org/10.1186/1471-2431-13-124