Redefining early detection for type 1 diabetes

Researchers have identified a protein pattern that, already at birth, looks markedly different in those who later go on to develop type 1 diabetes. The findings show that a combination of several factors during pregnancy increases the risk of the child later developing the disease. The study is published in Nature Communications and was led by researchers at Linköping University, Sweden, and the University of Florida, USA.

The race is not run at birth; I don't believe that. But factors very early in life play an important role in the risk of developing type 1 diabetes later on, and this study reinforces that."

Johnny Ludvigsson, Study Lead and Senior Professor, Department of Biomedical and Clinical Sciences, Linköping University

Ludvigsson led the study together with Eric W. Triplett at the University of Florida, USA.

Type 1 diabetes develops when the immune system overreacts and destroys the cells that produce the vital hormone insulin. Insulin plays a key role in regulating blood sugar levels. When the body can no longer produce insulin, the individual must receive insulin treatment for the rest of their life and may eventually develop serious health complications.

But the immune system may not be solely to blame for the onset of type 1 diabetes. Research has long indicated that the insulin‑producing beta cells in the pancreas are sensitive to stress, for example when they have to work intensively to meet the body's insulin needs. According to the researchers behind the study, beta cells may become more vulnerable to immune attacks if they are simultaneously stressed by other factors, such as infections, inflammation or various metabolic by-products. And these processes begin even before the child is born, according to the findings presented in the current study.

The researchers analysed blood taken from the umbilical cord at birth. In this cord blood they identified a pattern of proteins that is significantly different in children who later develop type 1 diabetes. The proteins examined are linked to inflammation and immune function and may reflect that processes causing inflammation and immune-mediated damage have already begun during pregnancy.

"It seems that with this protein pattern, we can predict more than 80 per cent of those who will later develop type 1 diabetes. This applies regardless of genetic risk. Some individuals develop type 1 diabetes without having a high genetic risk, and they show the same type of protein pattern at birth in our study," says Johnny Ludvigsson.

The researchers emphasize that the study is not intended to predict disease in individuals, but rather to identify the biological mechanisms that lead to the onset of the disease.

"This does not mean that diabetes is predetermined. It means that biology is being shaped during a period when systems are still highly adaptable," said Angelica Ahrens, lead author of the study and assistant research scientist in microbiology at the UF Institute of Food and Agricultural Sciences (UF/IFAS).

It is not possible to single out one factor as the cause. The findings should be seen as a first step in identifying interesting substances to investigate further. The researchers' long‑term goal is for their research to contribute to detecting the disease at an earlier stage than is currently possible. This could improve the chances of alleviating or even preventing the disease in the future.

The researchers also found that some of the proteins associated with future disease may themselves be influenced by certain PFAS substances (per‑ and polyfluoralkyl substances), so‑called 'forever chemicals', to which the mother has been exposed. Exposure to harmful environmental substances present in the world around us is not an individual choice, the researchers point out, but an example of factors that can be shaped through legislation and other societal regulation.

In this study, the researchers examined children from the ABIS study (All Babies in South‑East Sweden), led by Johnny Ludvigsson at Linköping University. Just over 16,000 children born in 1997-1999 have been followed from birth onwards. During childhood, roughly one child in a hundred develops type 1 diabetes. A large number of lifestyle and environmental factors have been mapped using questionnaires, and various samples have been collected. In the present study, the researchers analysed around 400 blood samples taken from the umbilical cord when the children were born.

"The primary value of this paper is that it suggests a new means to predict future type 1 diabetes using biological tissue, the cord blood, that is discarded at birth. The cord blood can be stored for future measurement of proteins in the sample. This represents an approach that doesn't require an invasive procedure for the newborn child (such as blood sampling), genetic testing - which has privacy concerns - or any future expensive testing in the child for autoantibodies in blood," says Eric Triplett, professor at the Department of Microbiology and Cell Science at the University of Florida.