Researchers at King's College London have been awarded £2.3m in funding from The Leona M. and Harry B. Helmsley Charitable Trust to investigate how changes during pregnancy and early childhood may influence a child's future risk of developing type 1 diabetes (T1D).
The project is led by Professors Deena Gibbons and Rachel Tribe and brings together researchers from across the Faculty of Life Sciences & Medicine.
The grant from the Helmsley Charitable Trust is awarded for the Prenatal Drivers of Infant Islet Autoimmunity (PISA) study and follows a previous (£1.6m) funding award from the same charity to initiate the study in 2022. The King's study is investigating whether different exposures in pregnancy influence fetal development to increase the risk of childhood autoimmunity in infants already at higher risk (i.e. those with a parent or close relative with T1D).
It is estimated that there are about 35,000 children and young people under the age of 19 living with diabetes in the UK, with 96% of these cases being T1D. The incidence of T1D in children has been increasing steadily over recent decades, and research shows dramatic increases in incidence since the Covid-19 pandemic.
While certain factors are known to influence a child's risk of developing T1D, such as a family history of the condition, the exact causes are unknown. The PISA study aims to understand whether the environment in the womb influences a child's future risk of developing T1D.
The study is recruiting 500 women from Guy's and St Thomas' and King's College Hospital NHS Foundation Trusts whose children are at greater risk of developing T1D. The team is collecting biological samples, including blood and placenta samples, from mothers and using pregnancy MRI scans to examine pancreas development in the fetus. They are also collecting a small amount of blood from infants at birth and during the first two years of life to study immune system development and the development of islet autoantibodies, an important early marker of the risk of developing T1D.
Using the data, the researchers are investigating whether maternal factors, such as infections during pregnancy, are linked to a child's risk of developing T1D. They are also examining whether changes in the developing pancreas during pregnancy, or changes in the placenta, are associated with a higher risk of developing the disease.
The research team is also utilising the eLIXIR Born in South London study cohort to identify children who go on to develop T1D. Using the mothers' medical records, they will then work backwards to look for patterns that could help explain why some children develop this disease and others do not.
Through these investigations, the team hopes to identify changes that precede T1D development, which could offer new options for prevention.
Identifying changes in the immune system either at birth or during post-natal development in children who subsequently progress to T1D will not only enhance our understanding of disease pathogenesis but also identify biomarkers of subsequent progression and potential targets for therapy. Considering the increase in prevalence of T1D in children, this is a very timely study.
Professor Deena Gibbons, Professor in Early Life Immunology in the School of Immunology & Microbial Sciences and project co-lead
This new phase of funding from The Leona M. and Harry B. Helmsley Charitable Trust will enable us to build on the unique strengths of the PISA study to understand how the in-utero environment shapes a child's future risk of developing type 1 diabetes. Importantly, our mother-child cohort, together with long-term follow-up and linkage through eLIXIR, will allow us to track health outcomes from pregnancy into childhood and beyond, providing unprecedented insights into the earliest origins of autoimmune disease.
Professor Rachel Tribe, Professor of Maternal and Perinatal Sciences in the School of Life Course & Population Health Sciences and project co-lead
"This grant also recognises the dedication of the PISA team working across the University, Guy's and St Thomas' and King's College Hospital NHS Foundation Trusts, our collaborators, and the generosity of the families who participate in the study, whose continued engagement makes it possible to follow children from pregnancy through early life and generate insights that could ultimately help prevent type 1 diabetes," added Professor Tribe.
