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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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
Issue number1
Publication statusPublished - 14 Aug 2013
Externally publishedYes


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

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