Diabetes: comprehensive prevention, early "vaccination"?

Interview with Dr. Peter Achenbach, Assistant Director of the Diabetes Research Institute, Supervisor of Immunophenotyping, Helmholtz Zentrum München

A diagnosis of diabetes often catches new patients off guard - for instance if they end up in the emergency room suffering from metabolic decompensation. Children are often affected by this. Their immune system destroys the insulin-producing cells in the pancreas early on in their lives, thus causing type 1 diabetes.


Photo: Smiling man with short dark hair and glasses - Dr. Peter Achenbach

Dr. Peter Achenbach; ©Dr. Peter Achenbach

It could be diagnosed early through a screening and possibly even prevented by regulating the immune system. In this interview with MEDICA.de, Dr. Peter Achenbach talks about how "Fr1da" is intended to help children and their families in Bavaria before the first symptoms occur. The study's objective is to promote comprehensive screening for diabetes, the early diagnosis of the harmful autoimmune response and a chance to slow down the immune system.

Dr. Achenbach, the Helmholtz Zentrum München in Bavaria is conducting two studies on the early detection and intervention in type 1 diabetes under the name "Fr1da". What is the project about?

Dr. Peter Achenbach: This is a pilot project. Within the scope of the "Fr1da" early detection study, we want to examine 100,000 children in Bavaria to determine whether they are in the early stages of type 1 diabetes. We subsequently offer prevention and training courses for the patients and their families to explain the disease and its symptoms and inform them about the required treatment. In doing so, we avoid the serious, often life-threatening complications that frequently arise when clinical symptoms of diabetes manifest in small children: approximately 30 percent of them suffer from ketoacidosis, excessive blood acidity. One in 400 children dies from this.

In the intervention study, we are also working on developing a new treatment plan during the early stages: administering insulin powder with food. This is meant to help us regulate the immune system to prevent or, at least, delay the onset and clinical symptoms of type 1 diabetes. Participation in the intervention study is an additional service for children who have been diagnosed with early onset type 1 diabetes.

Photo: Child's finger is pierced using a lancing device

The researchers working at "Fr1da" analyse a small blood sample to look for the first signs of the damaging autoimmune response that will cause diabetes later; ©Institute of Diabetes Research

You mentioned "pilot project". What is new about this?

Achenbach: This type of comprehensive screening that we have been offering since last year together with pediatricians, has previously not been done anywhere in the world. Previous studies usually only examined the relatives of diabetes patients who exhibit an increased genetic risk due to family history. In doing so, you are more likely to identify persons who will develop diabetes, but the majority of patients do not have affected family members. This is why these patients were previously not diagnosed with the early stages of type 1 diabetes.

The definition of type 1 diabetes has also changed. According to current textbooks, you are affected by the disease if blood glucose levels are high and if you exhibit clinical symptoms. Increasingly, however, a new perspective prevails: a person is already affected by type 1 diabetes if an acute autoimmune response to specific antigens is detected. This is now defined as the early stage of the disease and the point where we begin our research.

What conclusion are you currently able to draw regarding the prevalence of type 1 diabetes?

Achenbach: We are certainly not able to make any concluding statements at the present time. So far we have examined approximately 35,000 children in Bavaria. The prevalence of early onset in the two to five age bracket lies between 0.3 and 0.4 percent. This approximately equates to the current prevalence of type 1 diabetes throughout Germany. We know from previous studies, however, that this prevalence is generally increasing worldwide but does so especially rapidly in two to five-year-olds. Environmental factors are the rumored cause in interaction with genetic and immunological preconditions.

Photo: Physician takes a sample of blood from a little girl's finger

The "Fr1da" study aims to screen 100,000 children in Bavaria. A prevention study of this extent has been unique worldwide until now; ©Institute of Diabetes Research

How do you diagnose type 1 diabetes in the early stages?

Achenbach: The early stage is defined by detecting an acute autoimmune response with autoantibodies against at least two of the four known primary antigens: insulin, glutamate decarboxylase, insulinoma-associated antigen-2 and zinc transporter 8. For the screening, we let the pediatrician take a blood sample, usually with a small finger prick. The blood is subsequently tested for autoantibodies. We verify a positive result from the screening sample by taking a second blood sample. Not until then do we make the diagnosis: the patient shows early stages of type 1 diabetes. The children and their families are subsequently given the chance to participate in prevention and education programs as well as the intervention study.

During the course of the intervention study, children are orally ingesting insulin powder with food. What happens next inside the body?

Achenbach: The insulin does not enter the body in its metabolically active form, meaning it does not affect blood glucose. It is broken down in the digestive system and its peptides are presented to the immune system. This occurs via the mucosa-associated immune system that is specialized in developing immune tolerance to food components. We want to induce the development of regulatory immune cells that are meant to be active where the insulin antigen plays a role, namely the immune action on beta cells. The induced regulatory immune cells are meant to suppress the autoimmune reaction that ultimately leads to the clinical manifestation of type 1 diabetes.

Photo: Man holding his baby talks to a physician

The "Pre-Point early" study is explicitly aimed at children aged 6 months to 2 years of age with a high genetic risk of type 1 diabetes due to family history who have not yet developed any autoantibodies; ©Institute for Diabetes Research

During our "Pre-POINT" pilot study, we were already able to induce these types of insulin-specific regulatory immune cells in children who did not exhibit the autoimmune process in the body yet with a specific dosage of insulin powder. Theoretically, this could produce a long-term tolerance to insulin; these cells also develop a memory cell character. However, we don’t have any long-term data in humans yet.

There have been other approaches where people have been administered insulin doses, for instance in the form of nasal spray. What is the difference?

Achenbach: A number of these approaches is looking for ways to avoid insulin injections. However, our treatment does not want the ingestion of metabolically active insulin.

Our goal is to manipulate the immune system. We know from previous studies and both international as well as our pilot studies that the application, the target audience, the right age and the correct dosage are essential to achieving the desired immune responses. Although this has already been successfully demonstrated in animal models, the translation into human beings is always extremely difficult. There are visible effects but also still some need for improvement, which we are studying with the "Fr1da" insulin intervention study and the "Pre-POINTearly" study. The latter is explicitly aimed at children aged 6 months to 2 years of age with a high genetic risk of type 1 diabetes due to family history who have not yet developed any autoantibodies.

Photo: Timo Roth; Copyright: B. Frommann

© B. Frommann

The interview was conducted by Timo Roth and translated from German by Elena O'Meara.