A quarter century of children's diabetes study

Every year, about 600 Finnish children under the age of 15 are diagnosed with type 1 diabetes. The number is the highest in the world in proportion to population. For a total of 25 years already, the DIPP study has been collecting information on factors that may be relevant for the development of diabetes in children. Viruses are suspected to play a great role.

It has long been known that the siblings of diabetic children are also at a high risk of developing the disease. In other words, diabetes has a genetic background. “In addition to genetic predisposition, the development of diabetes requires some environmental factors to trigger it,” says Professor of Paediatrics Riitta Veijola from the University of Oulu and Oulu University Hospital. Veijola is the responsible investigator for the DIPP study in Finland.

Type 1 diabetes develops when the pancreas stops producing insulin. An autoimmune reaction damages the insulin-producing cells in the pancreas and the body’s white blood cells begin to produce antibodies. The emergence of autoantibodies indicates that the risk of the child developing diabetes has increased significantly.

It is still partially obscure what triggers this sequence of events. Cow's milk was suspected to be one of the factors, but this hypothesis was rejected a few years ago. “When children who were not given any dairy products during their first year were compared with those who consumed cow's milk, no difference was detected in their morbidity by the age of 10,” Riitta Veijola says.

To date, quite a lot of information has been gathered on the role of enteroviruses in the development of diabetes. “Apparently, even type 1 diabetes can manifest itself in various forms, and it is assumed that enterovirus may have triggered some types of the disease”, says Veijola.

Between 1980–2005, the number of children diagnosed with diabetes doubled. Over the last decade, the situation has stabilised to the current 600 diagnoses per year. If we compare the current figure to the situation in the 1950s, the number is six times higher today.

A similar increase in morbidity has been observed, for example, in Kuwait and Estonia in recent decades. There may be a specific factor in the modern living environment and the rise in the standard of living that promotes the development of diabetes.

Children also develop diabetes at a younger age than before. The increase in morbidity has been the highest among 0–4-year-olds.

“In the early years of my career, the diagnosed children were mostly in their teens, whereas today their average age is seven. We do not know why the disease currently develops at an earlier age,” Riitta Veijola says.

Children develop diabetes at a younger age than before, Professor of Paediatrics Riitta Veijola tells. 

 

Vast amount of research material collected in the DIPP study

When a family is told that their child has a tissue type that increases the risk of developing diabetes, the family decides whether they participate in the follow-up phase of the DIPP study.

During the child's first year, the family has an appointment related to the DIPP study every three months, where a blood sample is taken from the child, and he or she is measured and weighed. Information is collected on the child's diet, living environment and potential illnesses.

After one year, the interval between the visits gets longer. After appointments at the ages of 12 and 18 months, the visits continue once a year until the age of 15. If the family keeps all the appointments related to the study, a blood sample is taken from the child and other material collected 19 times. All data is recorded in an electronic database, and blood samples are stored for future research purposes.

If autoantibodies are detected in the child's blood sample, the follow-up visits will take place every three months. And at this point, also the blood sugar level is measured, and glucose tolerance tests performed.

In the most typical case, autoantibodies are detected in the child's serum already at the age of one or two, which was a major surprise for the researchers. “If at least two different types of antibodies occur, 85% of children develop the disease before the age of 15. The average time from the emergence of antibodies to the development of the disease is about three years,” Veijola says.

Since children tested positive for antibodies are monitored closely, the disease will not come as a surprise to the family. Preparedness helps: when children participating in the DIPP study develop the disease, they will avoid the life-threatening diabetic ketoacidosis. About four to six per cent of the children who develop diabetes outside the scope of the study develop severe ketoacidosis, which causes huge suffering and a lot of concern for the family. Severe ketoacidosis always requires intensive care, the cost of which is approximately EUR 10,000 per day.

It is already possible to delay the development of diabetes

Research is carried out hoping to find a preventive treatment for diabetes one day. There still seems to be a long way to go, but the results of an American study from last summer give some hope. Children and young people tested positive for antibodies were given drug therapy that delayed the development of diabetes by two years.

A drug study is also underway in connection with the DIPP study to determine whether the drug called Victoza prevents development of type 1 diabetes in children aged 10 or over who have been tested positive for antibodies. This drug is commonly used in type 2 diabetes to improve insulin production in the pancreas.

“If the development of diabetes can be delayed for a couple of years, we are talking about significant benefits in terms of both health and finances,” says Riitta Veijola.

In 2020, Finland will start studying a vaccine on adults that prevents infections caused by enteroviruses. Once the vaccine has been established as safe in adults, it can also be studied in younger age groups, including DIPP children. It is hoped that the enterovirus vaccine could prevent the development of type 1 diabetes in some children.

 

The family was prepared for Sami developing diabetes

Sami Tuovinen, currently on the second grade of the general upper secondary school, was diagnosed with diabetes when he was six. Participation in the DIPP study helped the family get prepared for diabetes and saved the boy from serious complications when the disease developed.

Sami Tuovinen was two years old when the first occurrence of autoantibodies was detected in the blood test. Diabetes was diagnosed just a few weeks before Sami turned six.

 

In January 2002, a cord blood sample was taken from Mervi Tuovinen’s new-born baby boy. Based on the tissue type, the sample showed that the boy had an increased risk of developing diabetes. The family was invited to participate in the DIPP monitoring study.

"Of course, I wanted to participate in the study when we were given this opportunity,” says Mervi Tuovinen.

During the first year, the family saw a DIPP research nurse for an appointment and blood tests every three months. When the child started to eat solid food, the family also had to keep an exact food diary for several days and take it to the appointments. Every crumb of food eaten by the child was recorded as well as the quality of the fat and milk used, and the vitamin preparations taken. All illnesses and potential drugs taken were always documented.

After one year, the visits took place every six months. Sami Tuovinen was two years old when the first occurrence of autoantibodies was detected in the blood test.

“That is when we began preparing for living with diabetes, because we were told that it was very likely that Sami would develop it", Tuovinen says.

The family had almost four years of time to get prepared, as diabetes was diagnosed just a few weeks before Sami turned six.

Around Christmas in 2007, Sami was tired and grumpy.

“At first, I thought the symptoms were due to all the Christmas bustle and excitement. Then I noticed that our Finnish Lapphund Vili was running around the boy quite concerned and never let the child out of its sight.”

The hospital had already given the Tuovinen family a blood glucose meter, just in case, and a single measurement revealed the reason for the boy's crankiness and fatigue: Sami's blood sugar level was far too high. The dog Vili had sensed the high blood glucose level, and even after the first time, it kept on giving warnings if Sami's sugar levels became too high.

The diabetes diagnosis was made at the hospital. The serious diabetic ketoacidosis could be avoided, because the family sought treatment rapidly, and Sami's condition was quickly restored. Then the family started learning to live their everyday life with diabetes.

“Even though the DIPP study has not yet explained why Sami developed diabetes, the mere involvement in the study has helped us a lot. When, after the occurrence of antibodies, we knew that Sami is likely to develop the disease, we were able to prepare for the future and interpret the symptoms right,” says Mervi Tuovinen.

Now, Sami is a 17-year-old upper secondary school student who leads a normal young man's life. The young man has been personally responsible for the treatment of his diabetes for a few years, even though the mother does still worry about her son.

 

Text: Satu Räsänen
Photos: Juha Sarkkinen

 

Last updated: 20.11.2019