Researchers at Lund University studied how age-related epigenetic changes might affect pancreatic cell functions and increase the risk of type 2 diabetes (T2D). Using a simple blood test, the team identified biomarkers reflecting such changes, and how they related to future T2D development. The biomarkers could predict the disease years before it occurs, allowing people to make important — and possibly disease preventing — lifestyle choices.
The article, “Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes,” was published in the journal Nature Communications.
Aging is a risk factor for T2D, as it can lead to insulin resistance and the loss of glucose tolerance. Eventually, aging beta pancreatic cells fail to respond to the increased demand for insulin production, and diabetes sets in.
Epigenetic alterations, which refer to changes in gene expression resulting from external causes, have previously been associated with several diseases, including T2D. Moreover, increased DNA methylation (a chemical change that can alter gene activity) has been associated with decreased expression of the insulin gene and a key transcription factor for beta cell development and function. Despite evidence associating DNA methylation to effects on glucose and insulin physiology, it is not known if aging is associated with DNA methylation of human pancreatic cells, and if these changes have any effect on beta cell function and T2D development.
Researchers in Sweden studied insulin-producing beta cells from deceased people, and focused on four specific genes, in which they found increased DNA methylation, which affected their activity. When these changes were copied in cultured beta cells, they proved to have a positive effect on insulin secretion.
The team then analyzed blood samples from participants of two separate research projects, in Denmark and Finland. These blood samples were compared with blood samples taken from the same participants 10 years later. The Finnish participants, who initially had higher levels of DNA methylation, were found to have a lower risk of T2D a decade later. Among the Danish cohort analyzed, higher DNA methylation in the first blood sample was linked to a higher insulin secretion 10 years later.
The analysis revealed that all the Danish participants were healthy at both time periods, while approximately one-third of the Finnish cohort had developed T2D.
“Increased insulin secretion actually protects against type 2 diabetes. It could be the body’s way of protecting itself when other tissue becomes resistant to insulin, which often happens as we get older,” Charlotte Ling, a professor and research project manager, said in a news release.
Researchers plan to do epigenetic whole-genome sequencing, to find markers with a stronger predictive potential and in a larger study population.
Still, they believe these findings might motivate at-risk people to change their habits. “You cannot change your genes and the risks that they entail, but epigenetics means that you can affect the DNA methylations, and thereby gene activity, through lifestyle choices,” Professor Ling said.
