Abatacept Prevention Study: Can Diabetes Be Stopped Already at a Precursor Stage?

The Abatacept study is pursuing a promising new approach for the prevention of type 1 diabetes. The drug Abatacept shows promise in suppressing the activity of dysregulated immune cells, thus preserving insulin production over a longer period or possibly even permanently. The prevention study of the Institute for Diabetes Research, Helmholtz Zentrum München, and the research group “Diabetes” of Technische Universität München began work in January. Abatacept has also proven to be effective in the treatment of other autoimmune diseases.

Initially, type 1 diabetes develops unnoticed. Often years pass by before first symptoms appear, although islet autoantibodies are already circulating in the blood of the affected individual, leading to the destruction of the insulin-producing cells in the pancreas. Recently, the research team led by Professor Anette-Gabriele Ziegler discovered that evidence of two or more specific islet autoantibodies is a sure sign of a precursor stage of the disease. In this context, that is why the research community refers to this stage as “pre-diabetes”. To diagnose this stage early on and to prevent its progression is the aim of Ziegler, director of the Institute for Diabetes Research, Helmholtz Zentrum München and head of the research group “Diabetes” of TU München and the research area Type 1 Diabetes in the German Center for Diabetes Research (DZD): “We now know that when the clock of the disease starts ticking, there is no way back – unless we intervene preventively in an effective way: Considering the present status of medical research, this is only possible in the form of prevention studies like the Abatacept study.”

How can pre-diabetes be recognized?
By means of islet autoantibody screening, the blood concentrations of four islet autoantibodies are determined. The name of these autoantibodies specific for type 1 diabetes are derived from the Langerhans islets of the pancreas. Among other kinds of cells, these cell clusters contain beta cells in which the hormone insulin is produced. Insulin is essential for the regulation of blood glucose. Islet autoantibodies bind to specific components of the beta cells, which are essential for the insulin metabolism. The relevant islet autoantibodies are named after these components: insulin autoantibodies (IAA) and islet autoantibodies against glutamic acid decarboxylase (GADA), tyrosine phosphatase (IA2A) and the zinc transporter 8 (ZnT8A). Screening for these islet autoantibodies enables the diagnosis of type 1 diabetes at an early stage, i.e. even before the first symptoms of the disease appear.
If at least two islet autoantibodies show up positive, the risk of clinically manifest type 1 diabetes is 51% after five years and 75% after ten years. Of 100 children who tested positively, 51 reached the stage of insulin dependence after five years and 75 after ten years. However, around the world diabetes researchers are working intensively to stop the natural progression of this disease through preventive treatments.

How shall Abatacept stop the development of type 1 diabetes?
The Institute for Diabetes Research and the research group “Diabetes” are part of the international network TrialNet. In collaboration with researchers from other countries, different treatments developed to stop the progression of the disease are tested. These efforts are also reflected in the international Abatacept study, which also plays an important role for the DZD because it contributes to establishing a Germany-wide infrastructure for studies on type 1 diabetes.
The aim of Abatacept is to suppress the activity of immune cells that attack the body’s own beta cells.
“Abatacept is an antibody-like, well-tolerated drug,” said Ziegler. “It inhibits the interaction between specific immune cells, the T lymphocytes, and thus slows the autoimmune process.” The drug is already approved for the treatment of other autoimmune diseases. In adults these are mainly rheumatoid arthritis and in children and adolescents juvenile idiopathic arthritis. An initial study with type 1 diabetics who were treated shortly after diagnosis for 24 months with Abatacept also showed a clear long-term improvement of beta-cell function. The residual insulin production was preserved longer.
First and second degree relatives of a type 1 diabetic (children, siblings, parents, grandchildren) between 12 and 45 years of age may participate in this study. To participate, the subjects must have at least two islet autoantibodies (all except IAA) in their blood and have normal blood glucose levels.

Why early detection?
Whether an interested individual meets the criteria for participation in the Abatacept study or another diabetes prevention study depends on the outcome of the islet autoantibody test. Each study has different enrollment requirements.
Another important benefit of early diagnosis of type 1 diabetes through islet autoantibody screening is that severe metabolic imbalances (ketoacidosis) can be avoided at the outbreak of the disease. In about one-third of all children and adults who develop type 1 diabetes, the disease is diagnosed by the appearance of a severe and sometimes life-threatening ketoacidosis. Ketoacidosis can lead to long-term impairment of brain function and cognitive abilities that must absolutely be avoided. An early diagnosis of diabetes in children with positive islets can prevent a ketoacidosis through occasional testing of urine and blood glucose. Research in the U.S., Scandinavia and Germany clearly shows that the number of metabolic disorders and ketoacidosis in children who have participated in islet autoantibody screening is extremely low.

How is islet autoantibody screening done?
The Institute for Diabetes Research, Helmholtz Zentrum München, offers relatives of patients with type 1 diabetes risk screening for the disease at no charge. For this purpose, a small amount of blood is needed, which can be extracted by a primary care physician or pediatrician and mailed to the Institute for Diabetes Research in Munich.
As part of the screening examination, each participant will receive individual counseling, and after the status of the islet autoantibodies has been determined, each participant will receive a report of the results. If autoantibodies are present, you will receive training and long-term medical care and, upon request, a referral to a local psychologist for a consultation or consultations.
Information on islet autoantibody/diabetes risk screening and on the Abatacept study:
Institute for Diabetes Research
Helmholtz Zentrum München
Ingolstädter Landstr. 1
85764 Munich, Germany

Research group Diabetes
Klinikum rechts der Isar
Technische Universität München
Chair for Diabetes and Gestational Diabetes
of Technische Universität München
Univ.-Prof. Dr. med. Anette-Gabriele Ziegler
Kölner Platz 1, 80804 Munich, Germany
Phone: 0800 - 828 48 68 (free call)