Epigenetic changes shown to cause type 2 diabetes

Epigenetic changes arise due to changes in environmental and lifestyle factors and can affect the function of genes. Whether epigenetic changes cause type 2 diabetes or is simply a marker of having type 2 diabetes remains a matter of debate. In addition, if epigenetic changes do cause type 2 diabetes, what genes were involved? A new study¹ by researchers at Lund University published in Nature Communications provides support for the idea that epigenetic changes can cause type 2 diabetes and have identified new genes that impact the development of the disease. The researchers studied epigenetics in pancreatic islet cells from donors and found 5584 (DNA methylation) sites in the genome with changes that differed between 25 individuals with type 2 diabetes and 75 individuals without the disease. The same epigenetic changes found in people with type 2 diabetes were also found in individuals with elevated blood sugar levels, which increase the risk of developing the disease. Since these same epigenetic changes were observed in people with type 2 diabetes and individuals at risk for the disease, it was concluded that these epigenetic changes were likely to contribute to the development of type 2 diabetes. The study therefore identified 203 genes with different expression in individuals with type 2 diabetes compared to the control group. The researchers found that the gene RHOT1 showed epigenetic changes in people with type 2 diabetes and that it also played a key role in insulin secretion in pancreatic islet cells. This was supported when the deletion of the gene expression of RHOT1 resulted in decreased insulin secretion. Having identified genes involved in the epigenetic changes, the next step was to develop a blood-based biomarker that can predict who is at risk of developing type 2 diabetes. To this end they investigated whether the epigenetic changes from the human pancreatic islet studies were reflected in blood of living people. They found that epigenetic changes in the blood of 540 people without the disease could be linked to the future development of type 2 diabetes in half of the individuals. Factors such as unhealthy diet, sedentary lifestyle, and ageing increase the risk of type 2 diabetes, and they also affect our epigenetics.

The development of a reliable epigenetic marker will enhance the ability to identify individuals who are at high risk of developing type 2 diabetes so that a more focused and aggressive intervention could be put in place to reduce the risk of developing type 2 diabetes. Alternatively, new methods can be develop to correct the activity of certain genes using epigenetic editing.