Type 1 diabetes is the most common metabolic disease in children and adolescents. The cause is an autoimmune reaction: The immune system's immune cells attack the insulin-producing beta cells in the pancreas and destroy them. If the destruction of the beta cells has exceeded a certain level, the metabolic disease becomes manifest. Due to insulin deficiency, the blood glucose levels rise. In Germany, about 30,500 children and adolescents under the age of 19 are currently affected by type 1 diabetes. The trend is increasing.
The exact background of type 1 diabetes has so far only been partially elucidated. It is known that type 1 diabetes is a polygenic disorder, i.e. that many different genes are involved in its development. In addition, environmental influences, but also the effect of sex hormones during puberty, play a role in the pathogenesis.
Current Research Questions
But how can we detect type 1 diabetes before the onset of the metabolic disease? What are the causes of the immune system malfunction? Which environmental factors have an influence on the pathogenesis of the disease? Is there any protection against the destruction of the beta cells? DZD scientists are working on the elucidation of mechanisms leading to the development of type 1 diabetes. In long-term studies they are investigating the association of genes, environmental factors and immune system for the pathogenesis of type 1 diabetes. The findings are helping to develop new approaches to the prevention and therapy of the disease.
Biomarkers Help to Detect Autoimmune Disease at an Early Stage
The autoimmune reaction proceeds insidiously and without symptoms for a long time. However, the respective autoantibodies can be detected by means of blood tests years before diabetes onset. Autoantibodies against cytoplasmic islet cell components (abbreviated ICA), insulin (IAA), glutamic acid decarboxylase (GADA) and tyrosine phosphatase IA2 (IA2-Ak) have the most diagnostic significance.
DZD researchers were able for the first time to show that in the affected children, at the beginning of the autoimmune reaction an elevated number of insulin-specific, follicular T-helper cells (TFH) are present in the blood. Analyses revealed that a molecule known as miRNA92a (miRNAs are non-coding RNAs, which play an important role in gene regulation and, in particular, when genes are silenced) are the impetus for a chain of molecular events, at the end of which is the increase of these immune cells.
But certain proteins in the blood of children can also predict type 1 diabetes – even before the first symptoms occur.
Early Treatment of Type 1 Diabetes
In the Fr1da Study in Bavaria, "Early detection of type 1 diabetes - treating it early", a free screening test to detect diabetes-typical antibodies is offered to all children between two and five years. The early diagnosis gives the children and their family valuable time to prepare for dealing with the disease. In addition, Fr1da shall aid in learning more about the causes of type 1 diabetes. The researchers are also hoping for new insights for prevention. The aim is to prevent ketoacidosis at onset of the disease and to optimize blood glucose levels by initiating insulin therapy at an early stage. In the long term, the risk of secondary diseases can thus be minimized. Similar projects have started in Saxony with the Freder1k Study and in Lower Saxony with the Fr1dolin Study.
Prevention of Type 1 Diabetes
Predicting type 1 diabetes as early as possible in childhood can help identify risk patients and possibly treat them prophylactically in the future. DZD scientists, together with international researchers, have made a major breakthrough in the prevention of type 1 diabetes. In the Pre-POINT study, they were able to trigger a protective immune reaction by oral insulin administration in children between two and seven years with an increased risk of diabetes. What is special about this is that the insulin was given prophylactically at a time when the children had not yet developed any autoantibodies.
In the follow-up study, Pre-POINTearly, researchers are currently investigating whether this effect can be confirmed by oral insulin in infants and young children between six months and two years of age, and whether type 1 diabetes can be permanently prevented. In the Fr1da Insulin Intervention Study, the oral administration of insulin shall also be used to promote the development of a protective, regulatory immune response. The aim of insulin desensitization is to induce immune tolerance to body-specific proteins and thereby to avoid autoimmunity. Should the vaccine also permanently prevent the disease, even in the case of larger numbers of participants, a vaccination against type 1 diabetes could possibly be offered throughout Germany in the future.
Identification of Risk Factors for Type 1 Diabetes
It is not yet clear why the body destroys its own insulin-producing beta cells in the pancreas. It is believed that a certain genetic predisposition increases susceptibility to type 1 diabetes. To date, more than 50 disease-related gene loci have been identified - in particular certain variants of the gene for human leukocyte antigens (HLA), which play a key role in distinguishing between endogenous and exogenous structures by the immune system.
Evaluations of the long-term study BABYDIAB show that children with certain variants of the gene IFIH1 (interferon induced with helicase C domain 1) have a more than a two-fold risk of developing type 1 diabetes.
Numerous findings suggest that environmental factors also play an important role in the development of type 1 diabetes: children born with caesarean sections have more than twice the risk of type 1 diabetes as children born spontaneously. These were results of an evaluation of the BABYDIAB study. Furthermore, viral respiratory infections in the first six months of life are associated with an increased risk of type 1 diabetes.
The aim of the international multicenter TEDDY Study (TEDDY = The Environmental Determinants of Diabetes in the Young) is to identify childhood development factors that lead to type 1 diabetes and the underlying autoimmunity. For this purpose, the study physicians are collecting a variety of data on vaccinations, infections, geographical differences, dietary habits, psychosocial factors and other environmental influences in children with risk factors for the disease.
Beta cells produce and store insulin in the body. In type 1 diabetes and in advanced stage type 2 diabetes the beta cells are destroyed. DZD experts are working to stop the destruction of the beta cells and/or to replace the beta cells.
In addition to the transplantation of insulin-producing islet cells from human donors, animal tissues or stem cells could also serve as a source for transplants.
Techniques for producing insulin-producing beta cells from embryonic or adult stem cells offer great medical potential.
New regenerative methods rely on dormant reserves in the patient’s body. Another alternative are “bioreactors”, a type of artificial pancreas.