Friday March 6 2009
Viral proteins were found in pancreas cells from children with diabetes
“A common gastric virus may trigger diabetes… raising hopes that a vaccine can be developed”, The Independent has reported. New research has found that enterovirus, which can cause vomiting and diarrhoea, can also attack cells in the pancreas and “trigger the immune reaction which leads to insulin-dependent diabetes”.
This study found evidence of enterovirus in the pancreases of 60% of 72 young people who died soon after being diagnosed with type 1 diabetes. There was “virtually no sign” of infection in the tissue of 50 deceased children without diabetes. These findings have raised hopes that a vaccine can be developed, but scientists would first need to identify which of more than 100 strains of enterovirus they should target. Another recent study has found that a certain gene that plays a role in fighting viruses also protects against type 1 diabetes, supporting the suggestion that viruses could play a role in the development of the disease.
Although the first study suggests enterovirus could trigger diabetes, there were limitations, and its results will need confirmation. This looks like a promising area for future research, but more studies will be needed to clarify whether an enterovirus vaccine might successfully tackle diabetes.
Where did the story come from?
Dr S J Richardson and colleagues from Peninsula Medical School, University of Brighton and Glasgow Royal Infirmary carried out this research. The study was funded by Diabetes UK, the Juvenile Diabetes Research Foundation and Coordinated Action of the European Union (TONECA). The study was published in the peer-reviewed medical journal Diabetologia.
What kind of scientific study was this?
This was a laboratory study that aimed to look for evidence of enterovirus infection in pancreatic tissue from people with and without type 1 diabetes.
Type 1 diabetes occurs when the body’s immune system attacks the insulin-producing beta cells in the pancreas. Genetics play a role in susceptibility to type 1 diabetes, but there are also (as yet unknown) environmental factors involved.
Past studies have suggested that enteroviruses may help trigger an immune response, which may lead to the development of diabetes, but the authors of this new report say that much of this evidence is circumstantial. Through this new study, the researchers wanted to establish how commonly pancreatic enteroviral infection occurred among young people with type 1 diabetes, and whether their bodies mounted an immune response to the virus.
The researchers obtained preserved pancreatic tissue from the autopsies of 72 young people (average age 12.7 years) who had type 1 diabetes. On average, these young people had developed diabetes eight months before their death. The researchers obtained ethical permission to use this autopsy tissue.
The researchers also obtained various preserved control tissues from autopsies. These came from five pancreases and hearts from neonates (newborns) who died from infection with Coxsackie virus; 11 normal neonatal pancreases, three normal neonatal hearts, 39 normal pancreases from children aged 6 weeks to 17 years; 11 pancreases from children with cystic fibrosis (average age 8 years); 69 normal adult pancreases, and 25 pancreases from adults with type 2 diabetes. Again, the researchers obtained permission to use these tissue samples.
Thin slices were cut from the tissue samples, and special techniques were used to look for a protein found on the surface of the enterovirus, called the enteroviral capsid protein vp1. The researchers also looked for other proteins (including PKR, which is involved in fighting off viruses), and other immune system proteins. The researchers also looked for insulin within the pancreas, to identify those islets (clusters of hormone producing cells) that were still producing insulin, and those that were not.
What were the results of the study?
The researchers found the vp1 protein from enterovirus in the pancreases of 44 of the 72 people (61%) who had type 1 diabetes. But the protein was found in only three of the 39 (7.7%) pancreases from neonates and children who did not have diabetes.
The vp1 protein was present in two of the pancreases from the 11 children with cystic fibrosis. When the medical notes of these two children were reviewed, the researchers found they also had diabetes. Ten of the 25 pancreases (40%) from adults with type 2 diabetes contained the vp1 protein, which was also present in nine of the 69 (13%) normal adult pancreases.
The researchers then looked at where the vp1 protein was found within the pancreases of 10 children with type 1 diabetes. These pancreases were of interest as they contained large amounts of the protein. The vp1 protein was found in 78.7% of the islets that were still producing insulin, and only 2.6% of those that were not. Further tests showed that the vp1 protein was found in the insulin-producing beta cells.
The researchers found that the anti-viral protein PKR was often found in the same islets as the vp1 protein: 87% of islets assessed in patients with type 1 diabetes had both proteins. There was no PKR in the pancreases of five young people who did not have diabetes.
What interpretations did the researchers draw from these results?
The researchers concluded that the enteroviral surface protein vp1 is commonly found in the islets of young people with recent-onset diabetes, but rarely found in the pancreases of young people without the disease. They suggest enterovirus may also play a role in type 2 diabetes, because the vp1 protein was also found in the pancreases of adults with the condition.
What does the NHS Knowledge Service make of this study?
This study has a number of limitations:
- The pancreatic samples were taken from people who already had diabetes, meaning it is not possible to establish whether the enterovirus infection occurred before they developed the condition. In order for the enterovirus infection to play a role in causing diabetes, the infection would have to occur before diabetes developed.
- The number of pancreases tested was relatively small, and results would need to be confirmed in a larger sample.
- The study did not report whether the researchers were blinded to the tissue samples they were preparing and assessing, or whether they were aware of which samples came from which individuals.
- Ideally, the presence of the enterovirus in these samples would be confirmed by looking for genetic material from the virus (RNA). However, this type of genetic material breaks down quickly, and is difficult to obtain from preserved tissue. Consequently, the authors did not attempt this type of testing. They suggest that their results need to be confirmed by looking for enterovirus RNA in fresh tissue from people with recent-onset type 1 diabetes.
Another study published this week has identified four rare genetic variants in a gene called IFIH1 that protect against type 1 diabetes. This gene produces a protein that is involved in mounting an immune response against viruses containing RNA. This finding also supports the suggestion that viral infections may help to trigger type 1 diabetes in susceptible individuals.
Although the study described above contributes to the evidence suggesting that enterovirus could be one of these triggering viruses, its results are not conclusive. More research will be needed before it becomes clear whether a vaccine targeting enterovirus can tackle type 1 diabetes.