Environmental Determinants of Islet Autoimmunity (ENDIA)
The ENDIA study is investigating the environmental factors that influence the development of type 1 diabetes in genetically susceptible people from before birth throughout early childhood.
The Environmental Determinant of Islet Autoimmunity (ENDIA) study is researching the causes of type 1 diabetes so that we can find ways to prevent it.
In Australia, type 1 diabetes in children is twice as common as it was 20 years ago. Because our genes don’t change over such a short period of time, this suggests our environment has changed, making at-risk children more likely to develop type 1 diabetes. Research has identified a number of environmental factors that may play a role in triggering the development of T1D, such as viruses, breastfeeding vs formula feeding, and changes in the gut bacteria, however we still don’t understand how these factors interact with each other and with a person’s genes to influence the development of type 1 diabetes.
The ENDIA study will follow pregnant women whose unborn baby will have an immediate relative with T1D. This could be the mother, the father, or a sibling. The babies and their mothers will be followed throughout pregnancy and the early years of life, and environmental factors such as food exposures, body composition, the timing and frequency of viral illnesses and the types of bacteria living in the gut, mouth and skin will be measured. If we can understand exactly what in the environment is harmful or protective, we can develop strategies to prevent T1D.
So, if you are a mum-to-be with type 1 diabetes, a dad-to-be with type 1 diabetes or have an older child with type 1 diabetes, then your family may be eligible to participate.
ENDIA is funded thanks to grants from the Helmsley Charitable Trust and the Australian Government-funded ARC Special Research Initiative, led by JDRF Australia. Read the media release.
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The overall aim of the ENDIA study is to identify environmental factors, and gene-environment interactions, that contribute to and protect against the development of islet autoimmunity and progression to T1D in children genetically at-risk of T1D. 1,400 infants with a first-degree relative with T1D will be prospectively followed from early pregnancy into childhood to investigate relationships between prenatal and postnatal environmental factors, the genome/epigenome and the development of islet autoimmunity and subsequent T1D. ENDIA will evaluate the microbiome, metabolome-lipidome, nutrition, bodyweight/composition, insulin resistance, innate and adaptive immune function and viral infections. A systems biology approach will integrate multi-omics analyses to explore hypotheses and mechanisms underlying the development of islet autoimmunity. The unifying hypothesis is that gene-environment interactions during prenatal and postnatal development drive the development of islet autoimmunity and T1D in children at-risk for T1D. The specific hypotheses are:
- The maternal microbiome during pregnancy and lactation differs in composition, diversity and functional products between mothers whose offspring do and do not develop islet autoimmunity and T1D.
- The microbiome differs in composition, diversity and functional products in children who do and do not develop islet autoimmunity and T1D during the first three years of life.
- Accelerated weight gain during pregnancy, and accelerated weight gain and insulin resistance during the first three years of life, is associated with an increased risk of islet autoimmunity.
- Viral infection during pregnancy and first three years of life modifies the risk of islet autoimmunity and T1D.
- A range of environmental factors acting though the microbiome/metabolome induce epigenetic modifications and consequent changes in gene expression that alter the risk for development of T1D.
1,400 pregnant women with T1D, or where the unborn child has a first-degree relative with T1D, will be recruited during the pregnancy and their children followed during the first three years of life to determine the relationship between environmental exposures, the genome/epigenome and the development of islet autoimmunity. Investigation will be during pregnancy (1– 3 points in the first, second, and third trimesters depending on the time of recruitment) and 3-monthly after birth for two years, then 6-monthly thereafter.
- Prospective samples will be collected for analysis of the microbiome from the gut (represented by stool), oral cavity, nares, skin and vagina during pregnancy and from breast milk during lactation(including colostrum) and 3-monthly in early childhood.
- Nutritional status and intake will be documented prospectively during pregnancy (from the first trimester) and lactation.
- Weight gain and physical activity (using validated tools ) will be measured prospectively during pregnancy.
- Nutritional status and intake in childhood will be documented by daily diary until weaning and then by multi-pass 24-h food recalls until 24 months, and from two years by the Australian Toddler Eating Survey.
- Fasting blood samples will be collected in childhood to measure insulin resistance.
Professor Jennifer Couper
The Australian Type 1 Diabetes Clinical Research Network, The Leona M and Harry B Helmsley Charitable Trust Fund, JDRF, NHMRC
The study is being conducted in Australia at:
- South Australia: The University of Adelaide Robinson Research Institute, The Women’s and Children’s Hospital
- Victoria: The Walter and Eliza Hall Institute, The Royal Melbourne Hospital, The University of Melbourne, Deakin University
- New South Wales: The University of NSW, The Children’s Hospital at Westmead, The Royal Hospital for Women, The St George Hospital
- Queensland: Mater Health Services – Brisbane, The University of Queensland
- Western Australia: Princess Margaret Hospital, The Telethon Kids Institute, The Harry Perkins Institute of Medical Research
Persistent islet autoimmunity defined as persistent elevation of > 1 islet autoantibodies on consecutive testing, including the most recent.
Development of type 1 diabetes
- Unborn child has a first-degree relative with T1D.
- Mother in first, second or third trimester of pregnancy or child less than six months of age
Caregiver has inadequate communication in English to provide informed consent.
It is anticipated that by the end of 2017, 36 children will test positive for islet autoantibodies, and by the end of 2021, up to 126 children will test positive. For a given exposure, there is a 90% power to detect a 5% difference in risk of islet autoimmunity.
Image: Dr Dorota Pawlak PhD, Director of the Australian Type 1 Diabetes Clinical Research Network