Open Access Open Badges Study protocol

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

Megan AS Penno1, Jennifer J Couper12*, Maria E Craig3456, Peter G Colman7, William D Rawlinson38, Andrew M Cotterill9, Timothy W Jones10, Leonard C Harrison11 and ENDIA Study Group

Author Affiliations

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

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BMC Pediatrics 2013, 13:124  doi:10.1186/1471-2431-13-124

Published: 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.

Trial registration

Australia New Zealand Clinical Trials Registry ACTRN12613000794707.

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