Abstract
BackgroundThe 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/designENDIA 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.DiscussionDefining 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 registrationAustralia New Zealand Clinical Trials Registry ACTRN12613000794707.
Highlights
The incidence of type 1 diabetes has increased worldwide, in younger children and those with lower genetic susceptibility
The strength of Environmental Determinants of Islet Autoimmunity (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
The central aim of the ENDIA Study is to identify the gene-environment interactions occurring during prenatal and/or postnatal development that drive the development of islet autoimmunity and Type 1 diabetes (T1D) in children genetically at-risk of T1D
Summary
The incidence of type 1 diabetes has increased worldwide, 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 rising incidence of T1D and gene-environment interaction Type 1 diabetes (T1D), one of the most common child hood-onset chronic diseases, is associated with enormous human and economic costs. The incidence of T1D is increasing worldwide [1] with a younger age of onset described in European and Australian populations [2,3]. In the 1980s the mean adjusted incidence rate of T1D in Australia was ~11 per 100,000 person-years [4,5]. International evidence to support this includes: (a) the reduced relative frequency of high risk genotypes in newly diagnosed children; (b) a less than 40% concordance of T1D in monozygotic twins; (c) discrepancies in disease incidence among genetically similar populations living in different regions, and (d) migration studies that show T1D incidence increases as populations move from low-risk to high-risk areas [6]
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