COVID-19 not likely linked to early stage of type 1 diabetes in children, study finds

More research is needed to understand the rise in type 1 diabetes diagnoses since the beginning of the pandemic.

The COVID-19 pandemic saw an increase in new cases of type 1 diabetes (T1D) around the world, but researchers have been unable to determine whether the virus which causes COVID-19 was connected to developing T1D, or if other factors during the pandemic led to this increase.

A new study, led by researchers at UNSW, published on Tuesday in JAMA Pediatrics, shows that in a cohort of Australian children, the SARS-CoV-2 infection was not linked to the early stages of T1D development, a hallmark of the condition known as islet autoimmunity. 

T1D is an autoimmune condition where the beta cells of the pancreas, which normally produce insulin, are mistakenly attacked by the immune system.

“Global research has explored whether SARS-CoV-2 – the virus that causes COVID-19 – increases the risk of type 1 diabetes, but the results have been mixed,” says Dr Ki Wook Kim from the UNSW Faculty of Science's School of Biotechnology & Biomolecular Sciences.

“While studies in Europe and the US have had conflicting findings, our study of 1500 Australian children found no link between COVID-19 and increased islet autoimmunity risk.

“We conducted the only Southern Hemisphere study to see if COVID-19 raises the risk of islet autoimmunity in Australian children. Islet autoimmunity signals the first sign of self-damage of the pancreas, a hallmark of T1D,” says Dr Kim.  

Rising cases of T1D

Researchers say there are environmental factors that ‘trigger’ the start of the immune attack in people who are genetically predisposed to T1D. The exact triggers remain unclear but there is evidence suggesting that certain viruses could contribute to the development of T1D. 

“Given the worldwide increase in type 1 diabetes diagnosis since the beginning of the pandemic, the pressing question became whether the increase in cases was a direct result of SARS-CoV-2 infections,” says Dr Gregory Walker, from the UNSW Faculty of Medicine & Health's School of Biomedical Sciences.

To date, evidence from research studies around the world has been mixed. Some studies have shown that COVID-19 increases the risk of islet autoimmunity while others have shown this is not the case. Another study also suggested that a COVID-19 infection may speed up the progression of T1D, from its early stages to a clinical diagnosis.

So, Dr Kim and Dr Walker, along with co-authors including UNSW Professor Maria Craig and Conjoint Professor William Rawlinson, set out to find out whether there was a link between a prior COVID-19 infection and the development of islet autoimmunity in an Australian setting.

The ENDIA study

The researchers are part of the Environmental Determinants of Islet Autoimmunity (ENDIA) Study – world-first research which aims to determine the causes and triggers of T1D.

Their latest study was funded by JDRF Australia and The Leona M. And Harry B. Helmsley Charitable Trust (Helmsley), which have supported ENIDA for more than a decade.

ENDIA tracks 1500 children – starting in the womb – who have a family member with T1D. It has already collected more than 165,000 samples, including nasal swabs, urine, stool and breastmilk samples.

To examine COVID-19 as a potential trigger, researchers collected blood samples from nearly 1300 children in the ENDIA study to look at signs of autoimmunity and evidence of past COVID-19. They also relied on surveys asking parents if their children had previously had COVID-19.

The study found the incidence rate of islet autoimmunity among the study participants remained the same during and after the COVID-19 pandemic, meaning there was no increase as COVID-19 cases increased in the community. The rate was also the same for children who had a past infection and those who did not.

Both these findings suggest that there is likely no link between having COVID-19 and developing islet autoimmunity in Australian children.

This contrasts with other viruses such as enteroviruses which have been associated with T1D development. Dr Walker says the differences seen in this study and past studies conducted around the world could be due to several factors, such as the demographics of the study participants.

For example, studies in the Northern Hemisphere focused on children with specific genetic markers linked to T1D risk, while the ENDIA study looks at children who have a close family member with T1D. Age was also a key difference, with the Australian study focusing on children aged zero to seven, while other studies focussed on infants or older children exclusively. Other factors include the design of the study and also how COVID-19 spread through different parts of the world, or differences in lockdown policies.

Dr Walker says there are other environmental factors involved in the development of T1D, such as an individual’s microbiome, nutrition and exposure to pollutants, all of which could have been impacted during the pandemic and contributed to the rise in T1D diagnosis.

“There are environmental factors that could have been influenced by the pandemic through changes in behaviour. For example, in lockdown, if children weren’t going to childcare, then they were less exposed, not just to viruses, but to other microorganisms such as bacteria,” says Dr Walker.

What’s next?

The ENDIA study team will continue working to uncover other environmental factors, including other viruses, which could be contributing to the development of T1D in Australian children.

“More research is needed to understand the rise in T1D diagnoses since the pandemic. We are currently investigating the role of gut-infecting enteroviruses as a potential trigger for islet autoimmunity,” says Dr Kim.

“If we can identify what triggers the development of islet autoimmunity, well before the development of type 1 diabetes, we can then put in place early intervention strategies, like vaccination, which can delay or even prevent people from getting the condition altogether.”