Editor: David L. Joffe, BSPharm, CDE, FACA
Author: Brianna Belton, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences
Better understanding of how certain viral infections, possibly including COVID-19, may increase the incidence of type 1 diabetes could lead to new strategies for prevention.
Type 1 diabetes is an autoimmune disease that results from the immune system attacking the pancreas’ beta cells. Once the beta cells are destroyed, no insulin can be produced, and type 1 diabetes develops. Although the exact cause of type 1 diabetes is unknown, there have been some associations determined, including the link between the autoimmunity of type 1 diabetes and enteroviruses. While this link between an enteroviral infection and type 1 diabetes is established, a causal relationship has not yet been determined. Studies have shown that beta cells express enteroviral receptors, which may cause the prolonging of the infection. Additionally, if the pancreatic beta cells have the same antigens as the virus, it can lead to autoimmunity development. The body starts attacking what is perceived as the intruding virus.
A case-control study, Type 1 Diabetes Prediction and Prevention study, was conducted based on a prospective birth cohort in Finland to evaluate whether enteroviruses in stool were linked to the detection of islet autoimmunity. In this study, stool samples were collected from 129 children with islet autoantibodies (case) and 282 children without antibodies (control). All children were screened for the presence of enterovirus RNA using reverse transcription–polymerase chain reaction (RT-PCR).
The children with autoantibodies had more enterovirus infections than those without (0.8 vs. 0.6 infections per child). With time-dependent analysis, it was determined that the infections occurred after a year before the first detection of islet autoantibodies (6.3 vs. 2.1 infections per 10 follow-up years). Enterovirus infections were detected more frequently in the case group versus the control. In the stool samples that tested positive for enterovirus RNA, sequencing was used to determine the viral genotype. Twenty-five different enterovirus types were detected, and the most frequent enterovirus types were coxsackievirus A4 (28%), coxsackievirus A2 (14%), and coxsackievirus A16 (11%). The results suggest that enterovirus infections are associated with the detection of islet autoimmunity with a time lag of about nine months to a year. This study’s findings also strongly support previous studies that suggest that a relationship exists between enterovirus infections and autoimmunity in type 1 diabetes.
This study is relevant because it is the most extensive study to evaluate enteroviruses in stool samples in relation to type 1 diabetes. Additionally, since the study was based on a prospective birth cohort, an analysis could be used to determine the time-dependent associations between enterovirus infections and the onset of beta–cell destruction. The downside of this study is that it was only carried out in one country, Finland. Also, in Finland, there is a lower frequency of enterovirus infections. Therefore, similar studies need to be conducted in more countries, especially in countries with higher enterovirus infections. Also, the determination of the presence of the viruses in stool samples may not lead to accurate results because many enterovirus types cause respiratory infections. Respiratory samples, as well as stool samples, may have yielded different results.
Enteroviruses are not the only viruses that can trigger type 1 diabetes. Since there has been a link connecting certain viral infections to type 1 diabetes, researchers are now looking at the implications for COVID-19. As the sponsors of a new clinical trial on COVID-19 and type 1 note, SARS Cov-2 virus enters the infected cells by binding to the ACE-2 receptor, which is abundant in many tissues including the pancreas. This means that SARS Covid-19 infection could potentially trigger the development of type 1 diabetes either by an activation of the immune system, or directly via beta-cell infection and destruction.
The exact cause of type 1 diabetes has not yet been determined, but it is believed to be due to a mix of genetic and environmental factors. The enterovirus’s presence has been associated with a higher incidence of type 1 diabetes; therefore, further investigation is warranted. In the cases where a virus is potentially the cause of diabetes onset, vaccinations may become routine to prevent those cases triggered by viral infections. It won’t help those predisposed genetically; however, it does show promise in reducing virus-triggered cases. There is still much to be revealed in terms of the causation of type 1 diabetes.
Practice Pearls
- This study further suggests that there is a relationship between enterovirus infections and type 1 diabetes.
- New evidence suggests that the COVID-19 pandemic may also contribute to the incidence of type 1 diabetes.
- The exact cause of type 1 diabetes remains unknown, but with more evidence emerging, the relationship between type 1 diabetes and viral infections is becoming more established.
Honkanen, H., Oikarinen, S: Detection of enteroviruses in stools precedes islet autoimmunity by several months: Diabetologia
Covid-19 Infection and New Onset Type 1 Diabetes. https://clinicaltrials.gov/ct2/show/NCT04623697
Brianna Belton, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences
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March 02, 2021 at 07:08AM
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