Antiviral medicine slows the development of type 1 diabetes

Disease and treatment 22. okt 2023 3 min Professor and Consultant Jesper Johannesen Written by Kristian Sjøgren

Research has kindled hope of mitigating the development of type 1 diabetes among children by suppressing viral infections and curbing the immune system’s attack on the insulin-producing cells.

In a groundbreaking trial, researchers from Denmark and Norway have shown that antiviral medicine can slow the development of type 1 diabetes among children who have been newly diagnosed.

The trial represents the culmination of several years of research that has linked viral infections to the development of type 1 diabetes.

According to a researcher behind the pioneering discovery, the study contributes to improving understanding of how to slow the decline in insulin production among children with newly diagnosed type 1 diabetes to ensure a better life with diabetes.

“People with type 1 diabetes who produce small but significant amounts of insulin of their own will have an easier illness trajectory because blood glucose will be more stable and more likely to be near normal as a consequence of the insulin-producing beta cells not being completely destroyed. This will probably also lead to fewer comorbidities in the long term,” explains Jesper Johannesen, Professor and Consultant, who works at both Steno Diabetes Center Copenhagen and the Department of Paediatrics and Adolescent Medicine at Herlev and Gentofte Hospital.

The research has been published in Nature Medicine.

The research was a Nordic collaboration carried out in Oslo by Knut Dahl-Jørgensen and Lars Krogsvold from the University of Oslo and Oslo University Hospital. Researchers from Tampere University in Finland, Linköping University in Sweden and the University of Cambridge in the United Kingdom also contributed to the study, and more than 20 international research laboratories participated.

Association on the agenda for some time

For years, scientists have hypothesised that viral infections can trigger type 1 diabetes.

Previous epidemiological studies have shown that many people develop type 1 diabetes after a viral infection, and some studies involving people with newly diagnosed type 1 diabetes have also shown that their insulin-producing beta cells are infected with enteroviruses, which are otherwise typically present in the gut.

The hypothesis behind the link between viral infections and type 1 diabetes has therefore been that enteroviruses can leak from the gut to the pancreas and infect the beta cells, and then the immune system attacks these cells, causing type 1 diabetes.

“We consider this a low-virulence state with a slowly growing viral infection in the beta cells to which the immune system reacts. We thought that fighting the viral infection might help to limit the immune system’s attack on the beta cells and save some of them and thereby the person’s own production of insulin,” says Jesper Johannesen.

96 children in the trial

The researchers wanted to test their hypothesis on children with newly diagnosed type 1 diabetes.

Type 1 diabetes is often quite aggressive for children, with the body rapidly not producing sufficient insulin and blood glucose levels therefore being constantly elevated.

Even if the destruction of beta cells is advanced at diagnosis, children often have some insulin production that can be salvaged.

The researchers included 96 children with newly diagnosed type 1 diabetes aged 6–16 years. The children were randomised to six months of daily treatment with the two antiviral drugs pleconaril and ribavirin or placebo.

The researchers then investigated how this affected insulin production to indicate the condition of the beta cells after one year.

“We are not the only researchers working to preserve the insulin production of people with type 1 diabetes after onset. Other research groups are doing experiments to inhibit the immune system’s response, but the principle is the same: finding ways to avoid the destruction of the beta cells in the pancreas by slowing down the immune system that destroys them,” explains Jesper Johannesen.

30% more insulin

The trial with the 96 children was a great success. The children receiving antiviral medication retained 20–30% more of their insulin production after one year than the children receiving placebo.

Jesper Johannesen says that these results will become clinically significant if this increased insulin production can be maintained.

“We are now monitoring the children to determine their illness trajectory and whether the groups will still differ after two years of follow-up. We have probably not completely eliminated the immune system’s attack on the beta cells; once the immune system has started to attack, getting it to stop again is very difficult. The viral infection may initiate the attack, but the immune system may well continue to attack the beta cells even after the viral infection has subsided,” says Jesper Johannesen.

Next trial already in the wings

According to Jesper Johannesen, the study is a great success since it potentially opens up additional opportunities to influence the development of type 1 diabetes. However, this is only one of several ways to make treatment for newly diagnosed children and adults more effective.

The researchers took saliva, blood and stool samples from the children and analysed them for changes in the concentrations of viruses and other biomarkers.

In addition, the researchers have already planned the next trials in the series for next year, in which they will combine antiviral medicine with immunomodulatory therapy, not only reducing what the immune system reacts to, but also its response.

“We will investigate the dose and duration of the antiviral therapy and determine what happens when we combine this with immunomodulatory therapy. We hope that two plus two will equal at least four and maybe even five,” concludes Jesper Johannesen.

Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial” has been published in Nature Medicine. Several authors are affiliated with Steno Diabetes Center Copenhagen at Herlev and Gentofte Hospital, which is partly financed by the Novo Nordisk Foundation.

Clinical paediatric endocrinology and diabetes; Clinical research in pediatric diabetology; Broad educational experience at pre-gradual, post-gradual...

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