Type 1 diabetes: new findings on the development of autoimmune diseases in children

When and why does type 1 diabetes occur in children? For the first time, researchers have conducted a long-term study
of infants and young children with an increased genetic risk of type 1 diabetes.
The findings have been published in the Journal of
Clinical Research.
The authors provide a unique picture of the development of autoimmunity
in which continuous blood glucose regulation develops in early childhood and its relationship.

POInT research has a unique advantage in studying blood glucose levels during autoimmune development

Within the framework of the Global Platform for Autoimmune Diabetes Prevention (GPPAD), the clinical primary prevention study POInT (Primary Oral Insulin Trial) was conducted in a multicenter study
in 7 clinical sites in 5 countries.
The purpose of POInT is to prevent the formation of islet autoantibodies that induce type 1 diabetes
.
The β cells that produce insulin in the pancreas of people with type 1 diabetes are destroyed, which is the result of
an erroneous immune response.
It was previously thought that metabolic changes occur close to the onset of clinical diseases, where pancreatic β cells are destroyed
by autoimmunity.
However, no one has carefully studied what happens when
autoimmunity begins.
Therefore, the POInT study frequently followed more than 1,000 children with type 1 diabetes with a genetic risk of 10% in the first few years of life, starting at 4 months of age
.
This allowed the researchers to precisely correlate
changes in blood sugar with the timing of the development of islet autoantibodies.

"Our findings have changed our understanding of
the development of type 1 diabetes.
We found that metabolic changes occur in the early stages of the disease, earlier than previously expected," explains
Anette-Gabriele Ziegler, director of the Helmholz Diabetes Institute (IDF) in Munich.
She conducted POInT research with an international research
team.
The team examined the blood glucose levels and islet autoantibodies
in the children participating in the study.

The findings provide new avenues for research

First, contrary to previous assumptions, the results showed that blood glucose concentrations shortly after birth were unstable
.
Instead, they decrease in the first year of life and then increase
again around the age of 1.
5.
"We were surprised
by the dynamic changes in glucose metabolism in the first few years of life.
They are likely to reflect changes in islets and suggest that we need to study glucose metabolism and the pancreas in greater depth in early life," says
Katharina Warncke, chief physician for pediatric pediatric endocrinology/diabetes and IDF scientist.
Importantly, the scientists found that blood sugar levels after meals were already higher two months before the islet antibodies were produced
, compared to children who did not develop autoimmunity.
This difference persists and increases
pre-meal values after autoimmunity.

Confusion about key events that induce an autoimmune response

The researchers were able to determine the dynamic changes in blood glucose levels in infants and young children and reflected peaks in islet autoantibody concentrations — a stage
that indicates islet cell activity and susceptibility.
"Changes in postprandial blood glucose levels shortly before the initial detection of autoantibodies suggest that there may have been an event that impaired islet function prior to the autoimmune response and caused the autoimmune response
.
As blood glucose values rise further after seroconversion, the injury or impairment appears to persist, leading to further glycemic instability," Warncke explains
.

"The observed changes in blood glucose levels associated with autoantibody formation are exciting
.
Now that we know that the beginning of the disease process is likely to work on the islets, we can focus on our research to find the cause of this chronic disease," says
Professor Ezio Bonifacio of the Center for Regenerative Therapy at the Technische Universit?t Dresden.

In conclusion, the scientists found that metabolic changes occur in the early stages of the disease, much earlier than previously thought: changes can occur simultaneously with, or even before autoimmunity
.
Researchers believe that excessive elevation of blood sugar levels after eating and shortly before antibody formation is associated
with changes in islet cell function.

The goal: to prevent new cases

Ziegler concludes: "Changes in glucose levels can therefore serve as an indicator of islet cell dysfunction and the beginning of potential autoimmunity to β cells in the future
.
" However, this requires in-depth research
on glucose metabolism and other biomarkers in early childhood.
Scientists are ultimately working to reduce the number of new cases of
type 1 diabetes.
In Western industrialized countries, 4 out of every 1,000 children are affected
.