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Prof. Anette-Gabriele Ziegler
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Interview Prediction and Prevention are Key for Counteracting Type 1 Diabetes

"With the help of type 1 diabetes screening and prevention studies, we want to stop or delay the clinical manifestation of type 1 diabetes in children. Our vision is a world without type 1 diabetes."

Prof. Anette-Gabriele Ziegler, Director of the Institute of Diabetes Research at Helmholtz Munich

Prof. Anette-Gabriele Ziegler is dedicated to identifying mechanisms and predictive markers of type 1 diabetes in early childhood. Her aim is to delay the clinical onset of this chronic disease and to develop novel therapies to prevent the initiation of autoimmunity.

You have just been awarded with the Paul-Langerhans-Medal for your achievements in the field of type 1 diabetes. What does this award mean to you?

AZ: This award recognizes the impact of type 1 diabetes on each individual patient, society as a whole, and the ongoing research dedicated to the prevention, early diagnosis, and treatment of the disease. It acknowledges our work regarding prediction and prevention of type 1 diabetes and highlights the importance of preventive medicine. The award will play a pivotal role in increasing the relevance of early diagnosis and preventive medicine for type 1 diabetes in our society – this makes me happy.

Why are you driven to prevent the development of type 1 diabetes?

AZ: Type 1 diabetes is one of the most prevalent chronic diseases in childhood, and the most prevalent metabolic disease. This condition still has a high burden, despite all the fantastic developments in glucose measurement and insulin injection devices, the challenge for families remains substantial. Consequentially, we need therapies that can delay or prevent the clinical manifestation of this disease. To achieve this, an early diagnosis and the ability to diagnose the risk of developing this disease are immensely important.

At the beginning of your career: What was your goal?

AZ: When I started to work in this field, I was given a first project: To contribute to one of the first immunotherapy studies worldwide. Patients with type 1 diabetes were treated with Cyclosporin A – a drug that has a dampening effect on the immune system. That study really excited me because it was the beginning of recognizing that type 1 diabetes is not only a metabolic disease but also an autoimmune disease and that there may be other treatment options than insulin.

“The first immunotherapy studies of type 1 diabetes excited me because this was the turning point from where on the disease was not only seen as a metabolic but also recognized as an autoimmune disease. I am proud to be involved in the development of novel therapies besides insulin from the beginning up until now.”
Prof. Anette-Gabriele Ziegler


Type 1 Diabetes in Short

Type 1 diabetes is the most common metabolic disease in children and adolescents. People with type 1 diabetes have an insulin deficiency. Insulin helps transport glucose from the blood into the cells. Type 1 diabetes patients have to supply insulin to their body every day to survive.

What are your findings since then?

AZ: We now understand much better how the disease develops and in the US (not yet approved in Europe), we have a first immune modifying therapy to delay the onset of type 1 diabetes. This drug is a milestone in diabetes research and in my career: We have now something available that could complement the insulin treatment – these therapies can change the course of type 1 diabetes and therefore make a big contribution to prevention.

Another important finding was, that the autoimmune process begins in early childhood, within the first two years of life. Thus, there exists a vulnerable period with a heightened risk of developing an autoimmune disease such as type 1 diabetes; importantly, the risk decreases substantially with age. Therefore, an early screening at preschool age and the ability to diagnose the risk to develop this disease already at birth is immensely important.

What Is Autoimmunity?

Autoimmunity is a process, where the immune system mistakenly attacks normal components of a person's body. In the case of type 1 diabetes, immune cells attack insulin-producing beta cells with the consequence of a chronic deficiency of insulin. People living with type 1 diabetes need lifelong insulin therapy.

What is the advantage of diagnosing type 1 diabetes as early as possible?

In this video, Prof. Anette-Gabriele Ziegler explains why early detection of type 1 diabetes is crucial. 

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AZ: Our Fr1da-study clearly shows that the risk of severe metabolic events like diabetic ketoacidosis and psychological stress for those affected and their families can be significantly reduced when the disease is diagnosed and treated as early as possible. Therefore, we have established the Fr1da screening in 2015, a public health screening for early markers of autoimmunity, so-called islet autoantibodies, in Bavaria, Germany. The screening allows us to detect children with a very early stage of type 1 diabetes, where the autoimmune process has already started but symptoms are not yet diagnosable.
Our aim: We want to improve clinical care and provide access to therapies, that delay the clinical manifestation of the disease with drugs, such as the already mentioned drug, named Teplizumab. 

What Is a Diabetic Ketoacidosis?

Diabetic ketoacidosis is a serious complication of diabetes mellitus caused by a lack of insulin. Symptoms are: loss of appetite, nausea and vomiting, followed by muscle cramps, palpitations, abdominal pain and a so-called ketoacidotic coma.

What were the next steps and relevant findings?

AZ: The realization that the first years of life are the time window in which the risk of developing autoimmunity is particularly high led me and my team to develop studies that elucidate the mechanisms of disease initiation right after birth: We found that early childhood respiratory infections and inflammation increase the risk of islet autoimmunity and that mild elevations in blood glucose levels occur before the onset of autoimmunity. This could indicate that there are environmental modifiers that affect and change the beta cells and only these changes then trigger the autoimmune process.

What does GPPAD stand for?

GPPAD stands for Global Platform for the Prevention of Autoimmune Diabetes. The platform aims to provide an international infrastructure for studies dedicated to preventing the development of type 1 diabetes. Nine sites in five European countries drive the vison of a world without type 1 diabetes. The aim of GGPAD is to identify infants with an elevated genetic risk of developing type 1 diabetes and to perform primary prevention trials aiming to reduce the incidence of islet autoimmunity and type 1 diabetes in children.

What kind of external factor could trigger the autoimmunity?

AZ: Viral infections are possible environmental trigger for autoimmunity: A number of observational birth studies like the BABYDIAB-, the TEDDY-, or the DIPP-stud haveshown that early viral infections  are associated with an increased risk for type 1 diabetes. The recent COVID-19 pandemic showed that the coronavirus SARS CoV-2 might be a trigger, too. In children with a high genetic risk of type 1 diabetes, a COVID-19 infection doubles the likelihood that these children will develop autoantibodies against the islet cells. This was shown by the POInT-study, in which children were examined before and during the pandemic. In addition, the risk of developing autoimmunity is around five times higher if children are infected at a very young age. 

Our idea is therefore, to use GPPAD to test whether vaccination against the  SARS CoV-2 coronavirus in the first year of life has an impact on the development of islet autoimmunity and type 1 diabetes in children with a very high risk of type 1 diabetes. 

AVAnT1A is the name of the recently launched prevention study. We are currently in the process of enrolling children at high risk of type 1 diabetes on the basis of Freder1k, the newborn screening.

AVAnT1A: What Is That?

AVAnT1A stands for Antiviral Action against Type 1 Diabetes Autoimmunity. It is GPPAD's third intervention study. It will investigate whether a vaccination against SARS-CoV-2 in the first year of life can protect children with an increased genetic risk for type 1 diabetes from developing an autoimmune process. Additionally, the study aims to examine therelationship between viruses and type 1 diabetes and to assess viral exposure over time by collecting stool and saliva samples from the participating children.

Video: Prof. Anette Ziegler explains the meaning of the AVAnT1A-study for children with type 1 diabetes.

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All your findings would not have been possible without the help of the children…

AZ: This is why we initiated the awareness campaign "K1DS ARE HEROS"! Their disease influences their daily life and they also support the development of new drugs. We honor and appreciate this the best we can!

What Does The Paul-Langerhans-Medal Stand For?

The German Diabetes Association (DDG) is awarding scientists in the field of diabetes research for their achievements in the field of diabetology with the Paul Langerhans Medal. The award is named after the physician Paul Langerhans who discovered the islets of Langerhans in the pancreas that are responsible for the insulin production. He also discovered the Langerhans cells of the skin; these are so-called dendritic or antigen-presenting cells and crucial for the immune response, thus the best connection between diabetes and immunology.

Latest update: May 2024

Find Out More About Prof. Anette-Gebriele Ziegler And Connected Research

Prof. Anette-Gabriele Zielger is the Director of the Institute of Diabetes Research.

Contact:   Profile: Prof. Anette-Gabriele Ziegler


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