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Twin study finds type 2 diabetes clues in epigenetic changes

A photo of a researcher in front of a machine.
Researcher Emma Nilsson has analysed microRNA in fat biopsies from identical twins with and without type 2 diabetes. Photo: Kennet Ruona

Identical twins share the same DNA, but one twin may suffer from type 2 diabetes while the other twin does not develop the disease. A study led by Lund University in Sweden has now discovered that there are differences in gene activity in twins where only one sibling had developed the disease. The researchers’ discovery could contribute to the development of new treatment methods.

“Identical twins have the same genetic background, sex and age, and they are therefore interesting to study for researchers seeking to understand the mechanisms behind diseases. We found an epigenetic change in twins with type 2 diabetes which provides us with new clues to the disease,” says Emma Nilsson, researcher in epigenetics and diabetes at Lund University Diabetes Centre (LUDC) and one of the main authors behind the study.

For the study, 14 pairs of twins from Sweden and Denmark were recruited. Within the sibling pairs, one of the identical twins had developed type 2 diabetes. The average age of the participants was 68 years and the twins who had developed diabetes had a somewhat higher BMI compared to their sibling.

Less activity

Epigenetic changes occur through DNA methylation, among other things, a chemical process that controls the function of genes. The process is affected by various environmental factors, such as diet, exercise and stress. The researchers analysed DNA methylation and microRNA in fat biopsies from the pairs of twins to increase their knowledge about why only one twin had developed type 2 diabetes. MicroRNA regulates the production of proteins in the cells. 

The researchers’ analyses showed that a gene responsible for producing a specific microRNA, microRNA-30, was less active in the twins with type 2 diabetes. This led to them having lower levels of microRNA-30 in their fatty tissue than their sibling. The same pattern was present in the control group, which consisted of 28 people with type 2 diabetes and 28 people without the disease. The participants in the control group were not biologically related to one another. 

“We were able to confirm our results in individuals with no twin siblings and this proves that our results are relevant to all people and not only to identical twins,” says Emma Nilsson.

Important piece of the puzzle

The researchers also conducted experiments in which they reduced the amount of microRNA-30 in cultured fat cells, to see how it affected the cells’ ability to take up glucose. 

In type 2 diabetes, the body becomes worse at processing blood sugar. This is partly due to the cells having become less sensitive to insulin. Insulin resistance causes an increase in blood sugar levels. The researchers’ experiment showed that cells with a smaller amount of microRNA-30 also had a reduced ability to take up glucose. 

“We see the same pattern in people with type 2 diabetes. The study is an importance piece of the puzzle in our work to understand the mechanisms behind type 2 diabetes. The more pieces of the puzzle we find, the better we will become at developing new drugs,” says Emma Nilsson.

Increased knowledge about the mechanisms behind the disease could lead to more effective treatment of type 2 diabetes. Many patients experience side-effects, or find it difficult to achieve good control of their blood sugar with the drugs currently available. The researchers plan to follow up on their findings in forthcoming studies. 

“Our study could be a step on the way to new treatment options in which microRNA is used as an active substance in drugs to treat patients with type 2 diabetes. Clinical studies are already underway in which microRNA is being tested as a drug against cancer, for example,” says Emma Nilsson.

The study, which is published in the journal Diabetes, was conducted in collaboration between researchers from Lund University, Sahlgrenska University Hospital in Sweden and Steno Diabetes Centre in Denmark.

Epigenetics, DNA methylation and microRNA

Epigenetic changes occur as a result of environmental and lifestyle factors and affect the function of genes. The body’s cells hold our genome, DNA, which contains genes. We inherit our genes and they cannot be changed. On the DNA are what are known as methyl groups that control the expression of the genes, i.e. how active they are. DNA methylation is an epigenetic process that can be affected by exercise, diet and lifestyle. MicroRNA are small, non-coding RNA molecules that regulate the production of proteins. A single microRNA can regulate many proteins in a cell or signaling pathway. The genes that code for microRNA can be affected by DNA methylation.
 

Funding

The study received funding from the Swedish Research Council, the strategic research area EXODIAB (Excellence of Diabetes Research in Sweden), Region Skåne (ALF funding), the Novo Nordisk Foundation, the Foundation for Strategic Research (SSF), the Svensson Siblings Foundation for Medical Research, the Swedish Diabetes Foundation, the Royal Physiographic Society in Lund, the Magnus Bergvall Foundation, the Åke Wiberg Foundation, the European Foundation for the Study of Diabetes (EFSD), the Torsten Söderberg Foundation and the Albert Påhlsson Foundation.

Portrait of researcher Emma Nilsson.

Contact

Emma Nilsson, diabetes and epigenetics researcher at Lund University
emma_a [dot] nilsson [at] med [dot] lu [dot] se

Link to Emma Nilsson's profile in Lund University's research portal

Brief facts about the study 

Subject: Type 2 diabetes, microRNA, epigenetics, DNA methylation, fatty tissue, insulin resistance, twin study 
Research field: Basic research, clinical research
Type of publication: Peer reviewed 
Study design: Quantitative study, researcher-initiated study, statistical correlation
Experimental investigation: In vitro 
Observational study: Cross-sectional study. Number of groups in the study: 2+2. Number of patients in the study: 28+56. Patient group/s: 14 monozygotic twins with type 2 diabetes and 28 people with type 2 diabetes as a control group. Healthy volunteers: 14 monozygotic twins and 28 individuals as a control group. Case control study.

Link to the study in the scientific journal Diabetes

EXODIAB

Several of the researchers behind the study are part of EXODIAB (Excellence of diabetes research in Sweden), a strategic research area at Lund University. The goal of the strategic research area EXODIAB is to develop new treatments and drugs that can prevent or cure the disease.