Type 2 Diabetes Linked with Epigenetic Changes

Diabetes is a widespread health issue that affects millions of people worldwide. The disease is complex and can develop due to a combination of genetic and lifestyle factors. Given its increasing prevalence, scientists worldwide are investigating the underlying genetic complexities and epigenetic factors of diabetes in more detail.

One question that researchers are interested in is whether epigenetic changes cause type 2 diabetes or if the changes occur only after a person has become ill. A new study by Lund University’s researchers now provides increased support for the idea that epigenetic changes can cause type 2 diabetes.

Epigenetic changes occur when environmental or lifestyle factors alter genes, affecting their function. These changes don’t alter the underlying DNA code; rather, they direct the gene on how it is expressed. DNA methylation is an epigenetic mechanism where methyl groups attach to genes. Earlier studies analyzing DNA methylation of selected candidate genes associated with type 2 diabetes have advanced to analyzing the entire epigenome using WGBS.

The study, led by Charlotte Ling, professor of epigenetics at Lund University, focused on cells that produce insulin, checking to see if there were epigenetic changes associated with blood sugar levels and if the changes could predict future diabetes using blood samples. The study considered various factors like gene expression, open chromatin regions, and histone modifications.

In previous studies, it has been shown that DNA methylation in the pancreas, where insulin is produced, may predict type 2 diabetes. As well, DNA methylation changes are also associated with type 1 diabetes and can serve as a marker to predict the disease.

In the current study, the researchers found 5,584 DNA methylation sites in the genome that had changes that were different in those with and without type 2 diabetes. Interestingly, these same epigenetic changes were found in people with elevated blood sugar levels as well, which is also a significant risk factor for developing diabetes.

“Those of us who study epigenetics have long tried to understand whether epigenetic changes cause type 2 diabetes or if the changes occur after the disease has already developed,” states Tina Rönn, lead author and researcher at Lund University. “Because we saw the same epigenetic changes in people with type 2 diabetes and individuals at risk for the disease, we conclude that these changes may contribute to the development of type 2 diabetes.”

Lund University’s study led to the identification of 203 genes that express differently in those with type 2 diabetes when compared to a control group. Specifically, the gene RHOT1 stood out within the epigenetic changes and critically affected insulin secretion. When the researchers worked with RHOT1 expression in donor cells that do not contain type 2 diabetes, the secretion of insulin decreased.

“When we examined the same type of cells in rats with diabetes, we found a lack of RHOT1, confirming the gene’s importance for insulin secretion,” explained Tina Rönn. The RHOT1 gene appears to be a key factor in the regulation of insulin in the body. Insulin itself is a hormone that controls the levels of blood sugar. Through understanding its role, targeted interventions could be investigated in the future.

Taking it another step further, Lund University’s researchers investigated whether or not the epigenetic changes that were observed in cells producing insulin were visible in the blood of living people. The results showed that epigenetic changes were found in the blood of 540 people who did not have diabetes, with these changes being linked to developing type 2 diabetes for half of the group in the future. With this finding, researchers could potentially develop a simple blood test that could potentially predict an individual’s risk of developing type 2 diabetes. This could allow for early and personalized intervention.

Ultimately, the goal of diabetes research such as this study is to pave the way for prevention strategies. If these epigenetic changes can be identified early, people could receive advice regarding changing their lifestyles in order to potentially reduce their risk of developing diabetes.

Charlotte Ling envisions, “If we succeed in developing an epigenetic biomarker, we can identify individuals with epigenetic changes before they become ill. These individuals can, for example, receive personalized lifestyle advice that can reduce their risk of disease, or we can develop methods that aim to correct the activity of certain genes using epigenetic editing.”

The human body is a complex and intricate world, but even the tiniest molecular changes could impact the understanding and intervention of a serious condition like type 2 diabetes. With this study from Lund University, the connection between epigenetic changes and developing diabetes becomes clearer. Moving forward, understanding the nuances of genes and their inner workings could create a healthier future.

Source: Tina Rönn
, et al. Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes. Nature, December 12, 2023.

Reference: Epigenetic changes can cause type 2 diabetes. Lund University. December 13, 2023.

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