Research

Diabetes - summary of articles, published during the spring of 2003

Wild bank voles carry a virus and get type1 diabetes
- Is the same virus the cause of diabetes among children and adolescents?

The text below summarizes the content of the articles that have been published in different scientific journals during the spring of 2003. The articles are written by Bo Niklasson, virologist and expert on diseases transferred from animals to humans, and Åke Lernmark, diabetes researcher.

Summary

It has been shown that bank voles have type1 diabetes, a discovery that may be of great importance for diabetes research. This is the first time that diabetes has been found among animals in the wild. The sick voles carry the so-called Ljungan virus, and their disease has presented striking resemblances to diabetes among children. Scientific results indicates that Ljungan virus also can cause diabetes among children. This, however, is not proven and the research continues.

Background to juvenile or type1 diabetes

Juvenile diabetes, or type1 diabetes as it is also called, is a large problem in the whole world. Sweden has, after Finland, the highest incidence of type1 diabetes in the world. The causes of the disease are yet unknown. Genetic factors play a significant role, but the major part of those who get diabetes have no close relatives with type1 diabetes. Different forms of stress are believed to play a certain part. But why is there a season variation in the number of new cases? And why does the incidence of new cases vary in different countries and often also in different parts of a country? These circumstances indicate some form of environmental factor. The majority of scientists think that this environmental factor is an infection, and a virus is the most common candidate. Of the different viruses known to infect humans, one group called picorna virus has been pointed out as a possible cause of type1 diabetes.

Bank voles with Ljungan virus get type1 diabetes

Danish, Swedish and American scientists have found that wild bank voles often get type1 diabetes. The discovery may be of great importance for diabetes research, since it provides us with a completely new tool of studying the disease, regarding both the cause of the disease and possible forms of treatment (see reference 6-7).

A novel virus has recently been isolated from bank voles. This new virus belongs to the so called Picorna virus family. From what we can tell from the facts available today, it has existed among rodents world wide for thousands of years. The virus has a Swedish name, since the first virus isolated came from a vole caught in the valley of Ljungan, near Sundsvall in the northern part of the country.  The Ljungan virus has been isolated from animals with diabetes (see reference 2).

 

Fig 1 shows a bank vole, the reservoir of Ljungan virus.	Fig 1
Fig 2	Fig 2 shows Ljungan virus by electron microscopy.

The virus has also been established among infected animals with a so called PCR-method. When you perform an autopsy on the animals, you find massive damage on the pancreas where the insulin producing cells (beta cells) are destroyed. With the help of antibodies marked with colour (immunhistochemistry) the Ljungan virus can be detected in the pancreas islets of diabetic animals, but not in the pancreas of the healthy animals. Figure 3 shows the pancreas from an animal with diabetes and figure 4 comes from a healthy control animal. The blue colour is glucagon producing cells around an islet. The red colour is Ljungan virus.

 

In figure 3 Ljungan virus can be detected in the damaged beta cells.	Fig 3
Fig 4	In figure 4 all beta cells are intact and no Ljungan virus can be detected.

Many similarities between type1 diabetes among voles and children

Scientists have been surprised to see that so many of the signs and symptoms in humans with type1 diabetes also are seen in the voles. Severe thirst and very large urine output is seen. High levels of glucose are found in both the urine and in the blood. So called “autoantibodies” that are used as an indicator of type1 diabetes exist also among voles with diabetes. The autoantibodies that are used in this diagnostics are called GAD, IA-2 and insulin antibodies. The scientists have treated the animals with insulin and have then seen the glucose values normalized. Animals not receiving treatment develop a condition called ketoacidosis and die. Ketoacidosis can also be lethal to humans.

Another interesting observation is that the voles develop diabetes in a much higher frequency when they are exposed to stress. We have exposed the animals to many varieties of stress in laboratories. At maximal stress as many as half the voles come down with the disease. Many scientists believe that stress also may be a contributing and provoking factor when children and adolescents are affected with the disease.

The fact that the same signs and symptoms occur both in voles and in man is of major importance. This implies that experiments using voles may generate valuable information also concerning human diabetes. Moreover it indicates that the disease in both species is caused by the same etiologic agent.

Does the Ljungan virus cause diabetes also among children?

In an earlier study (see reference 1) it has been established that the number of voles in the north of Sweden varies from one year to the other. With two to three years interval the number of voles increases and we get what we call a “vole year”. The following year almost every one of the voles is vanished. There may be up to 200 times as many voles in the wild during a vole year as there are during a year when there are only a few voles. Sweden has by its unique environmental protection program a remarkable collection of data, where one of the variables measured is how the number of small rodents varies from one year to the next in different parts of the country. Dr Birger Hörnfeldt at the University of Umeå is in charge of this program and is also participating in research of diabetes among rodents.

By comparing the number cases with type1 diabetes to the number of voles in the wild, the scientists were able to show a significant association between diabetes and the abundance of voles in nature.

Research is now in progress to see if the virus found among voles with diabetes causes diabetes among humans. Patients admitted to the Astrid Lindgren Children’s Hospital have been tested and children with recent onset of diabetes have been compared to a control group of healthy children of the same age. Children with diabetes had significantly more antibodies against the Ljungan virus than the control group.

The scientists want to emphasize that it is not yet considered to be proven that the Ljungan virus causes type1 diabetes in humans. Further research is necessary before we can link Ljungan virus to the disease in humans. The work resembles a crime investigation. You can find signs that a person has been at the crime scene, but that does not prove that he committed the deed.

It would be an immense breakthrough for science if you could identify an infectious agent causing diabetes in man. It would then be possible to prevent the disease by vaccination against the infection. The Ljungan virus is related to the polio virus and the hepatitis A virus among others, for which effective vaccines have been developed. With effective diagnostics tools the infection could the detected in an early stage and the disease could for example be treated by administration of antiviral compounds.