Pre-POINT Study: Immunization-like Insulin Treatment to Delay or Prevent Type 1 Diabetes


More and more children and adolescents are being diagnosed with type 1 diabetes, and at younger and younger ages. The number of new cases peaks in the age group of nine months to two years. As part of the international Pre-POINT study (Primary Intervention with Mucosal Insulin for Prevention of Type 1 Diabetes), Professor Anette-Gabriele Ziegler and her research team are studying an immunization-like insulin treatment as protection against diabetes. The siblings Amelie and Nick M. are two of the participants in the study.

Katharina M. and her two children Amelie (age six) and Nick (age four) travel more than 500 kilometers to see a doctor – even though they have no signs of disease. As participants in the Pre-POINT study, they travel by train once every three months from their home in North Rhine-Westphalia to the study center of the Diabetes Research Group in Munich.

The two children are healthy, but they are at high risk of developing type 1 diabetes like their father and Leoni, their eight-year-old sister. That is what the doctors conducting the study at Helmholtz Zentrum München, a partner in the DZD, are striving to prevent: For three years they have been testing an immunization-like insulin treatment to protect against type 1 diabetes in 16 children from all over Germany. Preliminary studies in the U.S. have already shown that insulin, absorbed as powder via the intestine, can delay and possibly prevent the development of this autoimmune disease. Insulin works here like an immunization treatment, which – in contrast to injections of insulin – does not influence blood glucose levels, but only trains the immune system. Two international studies shall now help determine the optimal dosage and dosage form. In the INIT II trial, treatment is administered as a spray with intranasal insulin; the participants in the Pre-POINT trial take the insulin in powder form in a capsule with their food.

Measurement of diabetes autoantibodies
During the course of the Pre-POINT study the dosage of the insulin is incrementally increased. On the basis of blood sample analysis, the researchers seek to optimize the dosage by determining the effect – if any – of each dosage. During the initial screening a blood analysis is performed to determine the presence of risk genes for diabetes. Follow-up examinations to measure diabetes autoantibodies in the blood take place every three months – later every six months. Thus, the individual disease risk for the young study participants can be determined: the more abundant the antibodies associated with type 1 diabetes in the blood, the greater the risk of developing the disease. However, the antibody type also plays a role, as well as specific genes that can either provide protection or even represent a risk for developing the metabolic disease, such as different forms of the HLA genotype (human leukocyte antigen). Environmental factors that could impact the development of type 1 diabetes are hormones, weight gain or diet.

How do parents deal with this certainty? “It’s not that I constantly think about whether my other children will get diabetes, too,“ said Katharina M. “But there are times when a child is exceptionally thirsty and I think: Could this be a symptom?“ After a short pause she added, “It was strange to read in black and white that both of my two younger children belong to a high-risk group,” said Katharina M. “Before it was so nebulous, now it is certain. However, we also know that the risk, by itself, will not lead to the disease. Several factors have to come together.“

Prevention of long-term damage
The M. family is now prepared, so that with the aid of examinations scheduled at short intervals for the study, a possible onset of type 1 diabetes can be detected and treated early, even before the appearance of clinical symptoms. Thus, life-threatening metabolic disturbances such as ketoacidosis can more likely be prevented, and long-term damage associated with poorly controlled blood glucose levels can be largely avoided. Analyses of other diabetes factors performed by the Institute of Diabetes Research at Helmholtz Zentrum München substantiate these findings. They have also shown that those children who participated in the studies spent less time in the hospital after diabetes onset than children in whom the disease risk had not been previously tested.

The family was in fact aware that the older daughter, Leoni, might become diabetic someday, because her father, Eckhard, has type 1 diabetes. Still, it was very surprising when Leoni showed the first symptoms at age three: “When we were on vacation just before Christmas I noticed that Leoni drank up a whole glass of water at one go,” Katharina said. “That was very uncharacteristic of her. First I thought that she understood now that she had to drink more. I somehow felt that something was wrong, but I didn’t want to believe it. We then decided to check her blood glucose levels – they were so high we didn’t get any measurement – the measuring devices only go up to 500 – so then you think: measuring error! The next morning after breakfast we measured again: once again no measurement. And so we broke off our vacation and spent Christmas and New Year’s Eve in the children’s hospital.”

Little effort, great value
Now the family wants to be better prepared. She gladly undertakes the long trip to the study center: “Nick always asks, 'Mommy, when will we go on the ICE train again?‘“, said Katharina. When asked about her motivation, she answered, “With relatively little effort, we hope to advance research. It is minimally invasive for the children, and if by doing this we can ultimately help other children, it’s worth it to us.”

The Pre-POINT study has been running since 2009. To date, none of the study participants have become ill. There have been no side effects. Participation is free, travel costs are reimbursed.

At present, additional participants can enroll in the study. Participation is open to children between 18 months and seven years who have a sibling or two close relatives (father, mother or sibling) with type 1 diabetes.

For more information, please contact  without any obligation:

Diabetes Research Group of TU München
Prof. Dr. Anette-Gabriele Ziegler
Kölner Platz 1
80804 Munich
Phone: 0800 8 28 48 68 (free hotline)