Environmental determinants of islet autoimmunity (ENDIA): a pregnancy to early life cohort study in children at-risk of type 1 diabetes
1 Discipline of Paediatrics, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia
2 Endocrine and Diabetes Department, Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia
3 Virology Division, Department of Microbiology, South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, NSW 2031, Australia
4 School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW 2052, Australia
5 Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia
6 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW 2006, Australia
7 Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
8 SOMS Faculty of Medicine, and BABS Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia
9 Mater Health Services, South Brisbane, Queensland 4101, Australia
10 Princess Margaret Hospital Department of Endocrinology and Diabetes, School of Paediatrics and Child Health; Telethon Institute of Child Health Research, University of Western Australia, Perth, WA 6008, Australia
11 Walter and Eliza Hall Institute, Parkville, Victoria 3050, Australia
BMC Pediatrics 2013, 13:124 doi:10.1186/1471-2431-13-124Published: 14 August 2013
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.
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.
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.
Australia New Zealand Clinical Trials Registry ACTRN12613000794707.