Epigenetics can pave the way for individualised treatment of type 2 diabetes
Epigenetics has become an important tool for researchers endeavoring to understand the causes and development stages of type 2 diabetes. In the future, epigenetic biomarkers could be used to predict type 2 diabetes and individualise its treatment. Diabetes and epigenetics researchers at Lund University summarise some of the most important advancements in a review article published in Nature Reviews Endocrinology.
The causes of type 2 diabetes are not entirely mapped out, and epigenetics is contributing with important insights. Charlotte Ling, professor of diabetes and epigenetics at Lund University, is one of the authors behind a review article on this topic, published in Nature Reviews Endocrinology. She has carried out research within the field for almost 20 years and has contributed to several studies mentioned in the review article.
“When I started my research career in epigenetics and type 2 diabetes, there were not many studies in this field. Since then, our knowledge has developed greatly. Now we know that we can affect our genome and risk of developing type 2 diabetes through our lifestyle choices. Our way of life can make us ill, but we can also reduce our risk by eating healthy foods and exercising on a regular basis,” says Charlotte Ling, research group leader at Lund University Diabetes Centre.
Important lifestyle factors
We inherit our genes, and they rarely change. However, lifestyle factors such as obesity, unhealthy eating, and physical inactivity, as well as ageing, can cause major epigenetic modifications in healthy individuals. There is mounting evidence that these factors also contribute to the development of type 2 diabetes.
DNA methylation, one of the mechanisms that causes epigenetic changes, is a chemical process through which methyl groups attach to the DNA molecule, affecting the function of genes. Several studies have identified altered DNA methylation in pancreatic islets, adipose tissue, skeletal muscle, and the liver in individuals with type 2 diabetes. In the future, epigenetic biomarkers could be an important tool for clinicians when they to individualise the treatment of type 2 diabetes patients.
“Hopefully, this kind of research will lead to the development of an epigenetic biomarker that can foresee who will develop type 2 diabetes. However, more research is needed before such a biomarker can be used in the clinic,” says Charlotte Ling.
The drug metformin has been used to treat type 2 diabetes for decades. Metformin lowers blood sugar levels in patients and reduces the risk of developing complications. However, not all patients respond to the treatment and those individuals are at risk of elevated blood sugar levels. Some patients also experience side-effects from metformin.
Charlotte Ling’s research group has discovered epigenetic biomarkers that predict which individuals with type 2 diabetes will benefit from the drug, and which are likely to suffer from side-effects.
“There is growing awareness withinn the health care community that patients with diabetes need tailored treatment. We hope to develop biomarkers that can be used by healthcare professionals to foresee who will benefit from metformin and other treatments of type 2 diabetes,” says Charlotte Ling.
Complications of type 2 diabetes
Epigenetics can also be used to develop markers that predict common complications of type 2 diabetes, which would allow for individualised treatment of patients. Charlotte Ling’s research group is currently developing biomarkers that can predict complications in type 2 diabetes, such as stroke, heart attack, and kidney disease. Charlotte Ling emphasizes how important it is that epigenetics and genetics collaborate in this endeavor.
“We need to collaborate with geneticists to identify clinically useful biomarkers. It is crucial that we are humble and search for the best combination of biomarkers,” says Charlotte Ling.
The article in Nature Reviews Endocrinology
Title: Epigenetics of type 2 diabetes mellitus and weight change – a tool for precision medicine?
The review article summaries epigenetics and type 2 diabetes as a field of research and discusses some of the important advances.
- Type 2 diabetes is a common metabolic disease that involves insulin resistance of adipose tissue, skeletal muscle, and the liver, as well as impaired insulin secretion from the pancreatic islets.
- The disease has a genetic component and is also strongly influence by external factors, such as exercise, diet, obesity, and ageing.
- Epigenetic alterations, including DNA methylation, are found in various tissues from patients with type 2 diabetes and are also associated with environmental factors known to increase the risk of the disease.
- Human studies demonstrate how the epigenome mediates the effects of both genetic variation and environmental exposures on gene expression and cell functions associated with type 2 diabetes and obesity.
- Epigenetic alterations are randomly affected by environmental factors and may be hereditary.
- Epigenetic marks can potentially be used as biomarkers for the prediction of type 2 diabetes, risk of complications, and response to therapy.
Link to the article in Nature Reviews Endocrinology
Authors of the article in Nature Reviews Endocrinology
The three authors of the review article carry out research at Lund University Diabetes Centre (LUDC) and the strategic research area EXODIAB – Excellence of diabetes research in Sweden.
Charlotte Ling, professor and research group leader of diabetes and epigenetics at Lund University
Karl Bacos, associate professor and researcher of diabetes and epigenetics at Lund University
Tina Rönn, researcher of diabetes and epigenetics at Lund University
Charlotte Ling, professor of diabetes and epigenetics at Lund University
+46 706 14 51 46
charlotte [dot] ling [at] med [dot] lu [dot] se
Charlotte Ling’s profile i Lund University’s research portal
Epigenetics and DNA methylation
Epigenetic changes occur when environmental or behavioral factors cause functional changes to the genome, the complete set of DNA contained in our cells. DNA methylation, one of the epigenetic mechanisms, is a chemical process through which methyl groups attach to the DNA molecule, affecting the function of genes.
When the first studies of epigenetics and type 2 diabetes were conducted over a decade ago, DNA methylation was analysed on selected candidate genes associated with the disease. Technological advances made it possible to analyse DNA methylation in the entire genome using a technique called whole-genome bisulfite sequencing (WGBS).
The research is supported by grants from the Swedish research council (EXODIAB: Excellence of diabetes research in Sweden), Swedish Foundation for Strategic Research (LUDC-IRC), the Diabetes Foundation, the European Foundation for the Study of Diabetes (EFSD), the European Research Council (Paintbox), Region Skåne (ALF), the Novo Nordisk foundation, Påhlsson foundation, EFSD/Novo Nordisk Foundation Precision Diabetes Medicine Award Programme and the Crafoord foundation.