Study provides unique picture of blood sugar dynamics and autoimmunity in early childhood

Study provides unique picture of blood sugar dynamics and autoimmunity in early childhood

When and why does type 1 diabetes manifest itself in children? For the first time, researchers conducted a long-term study of infants and young children at increased genetic risk for type 1 diabetes. The results have now been published in the Journal of Clinical Investigation. The authors provide a unique picture of the dynamics of blood glucose regulation in early childhood and its relationship to the development of autoimmunity.

The POInT study is uniquely suited to examine blood glucose levels during the development of autoimmunity

As part of the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD), the clinical primary prevention study POInT (Primary Oral Insulin Trial) is being conducted multicenter at seven clinical sites in five countries. POInT aims to prevent the formation of islet autoantibodies and thus the development of type 1 diabetes. In people with type 1 diabetes, a misdirected immune reaction leads to the destruction of the insulin-producing beta cells in the pancreas. It was previously thought that metabolic changes occur shortly before the onset of clinical disease and that pancreatic beta cells are destroyed by autoimmunity. However, no one had studied exactly what happens when autoimmunity sets in. Therefore, the POInT study carried out regular follow-up in the first years of life - starting at four months of age - in over 1,000 children with a genetically determined 10 percent risk of developing type 1 diabetes. This allowed researchers to accurately correlate changes in blood sugar with the timing of islet autoantibody development.

Our results change our understanding of the development of type 1 diabetes. We show that metabolic changes occur at an earlier phase of the disease than previously thought.”

Anette-Gabriele Ziegler, Director, Helmholtz Institute for Diabetes Research Munich (IDF)

She conducted the POInT study together with an international team of researchers. The team examined pre- and postprandial blood sugar levels and islet autoantibodies in the participating children.

Results provide new approaches for research

First, contrary to previous assumptions, the results showed that blood sugar concentrations are not stable shortly after birth. Instead, they decrease in the first year of life and then increase again at about 1.5 years of age. "The dynamic changes in glucose metabolism in the first years of life surprised us. They most likely reflect changes in the pancreatic islets and signal that we need to pay more attention to glucose metabolism and the pancreas in early life," says Katharina Warncke, chief physician for pediatric endocrinology/diabetology at the Department of Pediatrics and scientist at the IDF. Importantly, the scientists found that in the children who developed autoimmunity, compared to children who did not develop autoimmunity, post-meal blood sugar levels were already higher two months before islet antibodies were formed. This difference persisted and led to an increase in pre-meal levels even after autoimmunity.

Puzzle the key event that triggers the autoimmune response

The researchers were able to determine that the blood sugar levels of infants and young children behave dynamically and reflect the peak concentration of islet autoantibodies - i.e. h. This indicates a period of islet cell activity and vulnerability. "The change in post-meal blood glucose levels shortly before the first detection of autoantibodies indicates the likelihood of an event affecting the function of the islets that precede and contribute to the autoimmune response. As glucose levels continue to rise after seroconversion, the impairment increases." or the damage appears to persist and leads to further glucose instability,” explains Warncke.

"The observed changes in blood sugar levels associated with autoantibody formation are exciting. Now we know that the start of the disease process likely occurs in the pancreatic islets, and we can focus our research on finding the cause of this chronic disease." says Ezio Bonifacio, professor at the Dresden Center for Regenerative Therapies at the Technical University of Dresden.

In summary, the scientists found that metabolic changes occur at a much earlier stage of the disease than previously thought: changes can occur in parallel with autoimmunity or even precede it. The researchers suspect that the excessive increase in blood sugar levels after eating and shortly before the formation of antibodies is related to a change in the function of the islet cells.

The goal: avoiding new cases

“Changes in glucose levels could therefore serve as an indicator of dysfunction of the islet cells and the possible development of autoimmunity against beta cells in the future,” summarizes Ziegler. However, this requires intensive further research into glucose metabolism and other biomarkers in early childhood. The scientists' ultimate goal is to reduce the number of new cases of type 1 diabetes. Four out of every 1,000 children in western industrialized nations are currently affected.

About GPPAD:

Helmholtz Munich coordinates the “Global Platform for the Prevention of Autoimmune Diabetes” (GPPAD), an association of seven academic research institutes and hospitals in Europe that are jointly building an international infrastructure for studies on the prevention of type 1 diabetes. Studies on early genetic risk assessment and prevention of type 1 diabetes are currently underway in Belgium (Leuven University Hospitals), Germany (Rechts der Isar Hospital, Technical University of Munich; Carl Gustav Carus University Hospital, Dresden University of Technology; Children's and Adolescent Hospital on the Bult, Hanover), the United Kingdom (Oxford University), Poland (Warsaw Medical University) and Sweden (Skåne University Hospital, Malmö). GPPAD was launched in 2015 and is funded by the Leona M. and Harry B. Helmsley Charitable Trust in the United States of America.

On the people involved

Prof. Dr. Anette-Gabriele Ziegler, Director of the Helmholtz Institute for Diabetes Research Munich (IDF); Full Professor (W3), Chair of Diabetes and Gestational Diabetes, Medical Faculty, Klinikum Rechts der Isar, Technical University of Munich

Dr. Katharina Warncke, chief physician for pediatric endocrinology/diabetology at the Clinic for Pediatrics - a cooperation between the Munich Clinic and the TUM Rechts der Isar Clinic, and scientist at the IDF.

Source:

Helmholtz Munich

Reference:

Warncke, K., et al. (2022) Increases in blood glucose before and after the appearance of islet autoantibodies in children. Journal of Clinical Investigation. doi.org/10.1172/JCI162123.

.