When and why does type 1 diabetes manifest itself in children? Researchers have now investigated this question in a long-term study with over 1000 small children. The results show that blood sugar levels change abnormally before the typical autoimmune reaction against the insulin-producing beta cells of the pancreas occurs. This could open up new possibilities for early detection and prevention.
The hormone insulin is produced by the so-called beta cells of the pancreas and ensures that our body cells can absorb the sugar we eat and generate energy from it. However, in type 1 diabetes, the immune system attacks the beta cells. Those affected therefore have too little insulin. Since the absorbed sugar cannot be absorbed sufficiently by the cells, your blood sugar is too high if left untreated and is subject to strong fluctuations. The autoimmune disease is partly genetic and typically occurs in young children.
Elevated blood sugar levels early on
But how exactly does the disease develop? A team led by Katharina Warncke from the Institute for Diabetes Research at Helmholtz Zentrum München has now investigated this in a long-term study with more than 1000 small children who had an increased genetic risk of type 1 diabetes. From the age of four months, the research team regularly took blood from the children and determined the blood sugar levels and possible antibodies against the beta cells. The focus was on the question at which point in the course of the disease the autoantibodies appear.
"Previously, it was assumed that autoimmunity is initially silent and has no noticeable consequences for the metabolism until the late preclinical stages," explains the research team. However, the blood samples showed a different result: “Blood sugar concentrations were elevated early on in children who developed autoantibodies against the beta cells,” report Warncke and her colleagues. About two months before the first autoantibodies were detectable, the blood sugar levels of the affected children rose sharply - initially only after eating, later also before eating.
Changes in beta cells before autoimmunity?
“Our research results are changing the understanding of how type 1 diabetes develops. We show that metabolic changes occur earlier in the disease process than previously thought,” explains Warncke's colleague Anette-Gabriele Ziegler. Abnormalities could already be observed within the first year of life. Contrary to previous assumptions, the blood sugar concentrations never reached a stable state. Instead, they initially fell between the fourth and 18th month of life and then rose significantly. The last examination in the study took place when the children were about 3.6 years old.
"The dynamic changes in blood sugar levels during the first years of life are amazing," says Warncke. “Presumably early changes in the pancreatic islets are reflected here. This is a clear signal that we need to investigate more intensively the relationship between sugar metabolism and the pancreas during the first phase of life.”
Early detection and possible prevention
The current results suggest that the autoimmune reaction against the insulin-producing cells is not the trigger but a consequence of the disease. "The sharp change in blood glucose levels shortly before the first detection of autoantibodies suggests an event that impairs beta cell function. This event precedes the autoimmune response and contributes to its development. Since the beta cell function continues to deteriorate after the first antibody formation, it appears that there is permanent damage to the islet cells that destabilizes blood sugar regulation,” Warncke explains.
The findings could help to identify type 1 diabetes earlier in children with a genetically increased risk. “In the future, changes in blood sugar could serve as an indicator of islet cell dysfunction and the possible onset of autoimmunity against the beta cells,” says Ziegler. Further research could make it possible to counteract this autoimmunity at an early stage and thus prevent the development of the disease.
Source: Katharina Warncke (Helmholtz Zentrum München) et al., The Journal of Clinical Investigation, doi: 10.1172/JCI162123