Type 1 diabetes could begin in the womb, new research suggests

Until recently, it was thought that children under six months could only develop neonatal diabetes, which is caused by a genetic mutation affecting insulin-producing cells in the pancreas, and not type 1 diabetes, where the same cells are destroyed by an immune system attack. As people with neonatal and type 1 diabetes need different treatments, it’s incredibly important they get the correct diagnosis.

In research published in Diabetologia, the journal of the European Association for the Study of Diabetes [EASD], scientists studied a group of children who had developed diabetes before six months, but who didn’t have any of the genetic mutations known to cause neonatal diabetes. The team from the University of Exeter, King’s College London and the Pacific Northwest Research Institute in Seattle wanted to find out if the children in fact had type 1 diabetes.

They compared 166 of these children with children with confirmed neonatal diabetes and a third group who were diagnosed with type 1 diabetes at an older age (6-24 months). The team studied their genes and immune system, and looked at how much insulin the children could produce on their own. They concluded that the combination of a high genetic risk for type 1 diabetes, signs of an immune attack on insulin-producing cells and low insulin-producing capacity, all point to the existence of type 1 diabetes in children under six months.

This is the first time an autoimmune condition that isn’t caused by a single genetic change has been seen in children this young.

The research team also discovered that children with this very early onset type 1 diabetes had a lower than average birth weight – and the lower their birth weight, the earlier their type 1 diabetes was detected. Those diagnosed after six months were born at a normal weight, suggesting that low-birth weight was a specific feature of very early onset type 1 diabetes.

Usually a foetus begins making insulin in the womb, helping them to grow. These new findings raise the question of whether the immune attack behind type 1 diabetes could start before birth in some babies, leading to reduced insulin production and consequently lower birth weight. This challenges scientists’ current understanding of the immune system in early life.

The researchers now want to study this rare form of very early onset type 1 diabetes in more detail, to understand how it might be possible for the immune system to go rogue before it’s fully formed.

Dr Matthew Johnson, Exeter Centre of Excellence in Diabetes (ExCEED) E3 Research Fellow at the University of Exeter, said: “This study proves that type 1 diabetes can present in the first few months of life, and in a tiny subset of infants may even begin before birth. We also found that diabetes diagnosed so young was associated with rapid progression to complete destruction of insulin producing beta cells.”

Dr Richard Oram, Diabetes UK Harry Keen Fellow at the University of Exeter, said:
“The next phases of this work, where we study the immune system in more detail, will hopefully help explain how it is possible for type 1 diabetes to develop so early and whether these insights could open up new ways to prevent or treat the condition in the future.”

Dr Elizabeth Robertson, Director of Research at Diabetes UK who co-funded the research, said:
“By revealing for the first time the existence of type 1 diabetes in the very first few months of life, these important findings rewrite our understanding of when the condition can strike and when the immune system can start to go wrong. We now need to piece together how and why type 1 diabetes can develop at such a young age.

“This could also unlock crucial insights into causes of type 1 diabetes more generally in people of all ages, and will be essential to develop treatments that stop or prevent this life-altering condition in babies.”

This research was funded by Diabetes UK, Research England’s Expanding Excellence in England (E3) fund and The Leona M. and Harry B. Helmsley Charitable Trust.

The full paper can be accessed here: https://doi.org/10.1007/s00125-020-05276-4