Epigenetic Marks Indicate Early Type 1 Diabetes Risk

We hear a lot about the rise in type 2 diabetes worldwide, which primarily affects people in their 40s and 50s. But the same is also true for the less common type 1 diabetes (T1D). Global rates for this autoimmune disease have been increasing in recent years, and the trend is very troubling. T1D usually occurs in younger people and has a greater potential for causing disabilities and early death.

No one knows exactly why this disease has risen significantly over the years. Although T1D has a strong genetic component, experts agree that genetics alone cannot explain the reported number of heightened incidents. Environmental factors must play a role in the increase. Because epigenetic changes affect how genes work and are influenced by the environment, this area of study could bring insight into understanding more about the pathogenesis of T1D.

Researchers from the University of Turku, Finland have been investigating the underlying epigenetic mechanisms involved in T1D for some time. Their findings, presented recently in two different papers, have linked certain epigenetic marks to the initiation of the disease. Testing for these markers could determine risk and allow for the possibility of early intervention.

“We uncovered previously unknown, early-onset epigenetic changes”, said professor Riitta Lahesmaa, Director of Turku Bioscience Centre. “They offer us new opportunities to further develop ways to identify children who have a risk of developing type 1 diabetes even before they get sick.”

Prior research has found that children who develop multiple autoantibodies are more likely to progress to T1D. However, the presence of these antibodies in the blood essentially indicates that the disease is already ongoing.

The researchers here sought to determine molecular changes before seroconversion, allowing a longer window for intervention. They aimed to single out epigenetic biomarkers for T1D, like changes in DNA methylation and aberrant microRNAs (miRNAs) expression.

“Our observations on epigenetics are extremely important as our goal is to develop methods and tools to prevent the onset of type 1 diabetes in children who are at risk of developing the disease,” said professor Laura Elo, Director of the Medical Bioinformatics Centre at Turku Bioscience.

Finland, where the research was conducted, has the unlucky distinction of having the highest rate of T1D in the world. Approximate 0.9% of the population is afflicted with this insulin-dependent disease, with about 58 cases per 100,000 children being diagnosed every year. (By contrast, the US reports 24 cases per 100,000/year.)

In addition to the genetic element of T1D, most researchers suspect there may be a connection between certain environmental factors in the country and incidence rates. Hypotheses include excessive cleanliness, loss of biodiversity from large urban areas, and exposure to regional toxins.

For both studies, the researchers used next-generation sequencing techniques, like RRBS and miRIP-seq, along with scientific computation and artificial intelligence for their data analysis. Blood samples were longitudinally collected from children before and after T1D diagnosis and matched with controls.

One study focused on identifying DNA methylation changes in genes associated with T1D, while the other observed changes in miRNA levels. Each was able to link changes in these mechanisms to the occurrence of T1D.

Although the findings are preliminary, the overall results are promising, as they provide novel insights into the epigenetic changes associated with T1D. The expectation is that further studies based on the data could lead to diagnostic tests that may allow clinicians to better predict and manage T1D.

Source 1: I. Starskaia, et al. Early DNA methylation changes in children developing beta cell autoimmunity at a young age. Diabetologia, February 10, 2022.

Source 2: Tomi Suomi, et al. Type 1 Diabetes in Children With Genetic Risk May Be Predicted Very Early With a Blood miRNA Diabetes Care, March 1, 2022

Reference: Type 1 Diabetes Can Be Predicted with Epigenetic Changes. University of Turku, March 2, 2022.