The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Epigenetic markers predict complications in patients with type 2 diabetes

Photo of researcher in the lab.
Charlotte Ling and her research group have studied DNA methylations in the genome of different patient groups with type 2 diabetes. Photo: Kennet Ruona

A new study by researchers at Lund University supports the notion that patients with type 2 diabetes should be divided into subgroups and given individualised treatment. The study demonstrates that there are distinct epigenetic differences between different groups of patients with type 2 diabetes. The epigenetic markers were also associated with different risks of developing common complications in type 2 diabetes, such as stroke, heart attack, and kidney disease.

“We show that there are distinct epigenetic differences between subgroups of patients with type 2 diabetes. The epigenetic markers are associated with different risks of developing common complications in diabetes, such as heart attack, stroke, and kidney disease,” says Charlotte Ling, professor of diabetes and epigenetics at Lund University and lead author of the study, published in Diabetes Care.

An acclaimed study by researchers at Lund University Diabetes Centre (LUDC), published in 2018, demonstrated that it is possible to divide type 1 diabetes and type 2 diabetes into five subgroups. In November 2021, the same authors published a new study which highlighted genetic differences between the four subgroups of type 2 diabetes, suggesting different causes of the disease. 

The latest study by LUDC-researcher Charlotte Ling and her colleagues shows that there are also epigenetic differences between the four subgroups with type 2 diabetes. The epigenetic markers can be developed to be used to predict common complications of type 2 diabetes, which would allow for tailored treatments of patients.

“Many patients with type 2 diabetes are offered standard treatments by the health care system, but growing evidence suggests that these patients need tailored treatments. Our new study adds to the evidence base that it is clinically relevant to classify patients with type 2 diabetes into subgroups to allow for more personalised treatments,” says Charlotte Ling, who leads a research group in diabetes and epigenetics at Lund University Diabetes Centre.

Risk scores 

The new study encompasses 533 individuals recently diagnosed with type 2 diabetes from two population-based cohorts in Sweden. The authors measured DNA methylations in the blood at 800.000 sites in the genome of all participants. DNA methylation is a chemical process through which methyl groups attach to the DNA molecule, affecting the function of genes. The researchers found that the four subgroups had different levels of DNA methylation at 4.465 sites.

The findings were used to develop epigenetic risk scores to predict common complications of type 2 diabetes. Epigenetic markers associated with the subgroup SIRD (severe insulin-resistant diabetes) and MARD (mild age-related diabetes) could predict an increased risk of developing heart attack, stroke, and kidney disease. Epigenetic markers associated with the patient group MOD (mild obesity-related diabetes) could predict a lower risk of developing these diseases. 

“Heart attack and stroke are responsible for most deaths among patients with type 2 diabetes. Kidney disease causes a lot of suffering and is very costly for society, as many patients need dialysis treatment. An epigenetic biomarker that can predict complications at an early stage would make preventive actions possible,” says Charlotte Ling. 

Clinical biomarkers

The authors will need to verify their results in other population-based cohorts. They are also planning to study DNA methylation in tissues from, for example muscle, adipose tissue, liver, and the pancreas of the four subgroups with type 2 diabetes. 

“It is relatively easy to develop a blood-based epigenetic biomarker. However, we need to carefully study the prediction accuracy of such a biomarker, which is why we are following up our results in other population-based cohorts. Long term, we would like to develop clinical biomarkers that can be used to improve the individualised treatment of patients with type 2 diabetes,” says Charlotte Ling. 

Epigenetic differences between the four subgroups with type 2 diabetes

SIDD (Severe insulin-deficient diabetes)
SIDD is characterised by early onset, low insulin secretion and poor metabolic control. DNA methylations in 56 sites in the genome were unique for the subgroup. Epigenetic markers associated with this group could predict a lower risk of developing heart attack and stroke. 

SIRD (Severe insulin-resistant diabetes)
SIRD is characterised by late onset, obesity, and severe insulin resistance. This group showed DNA methylations in 74 sites that were unique for the subgroup. The epigenetic markers associated with this group could predict an increased risk of developing heart attack, stroke, and kidney disease.

MOD (Mild obesity-related diabetes)
MOD is distinguished by early onset, obesity, and a relatively mild disease in terms of the progression of hyperglycemia. MOD showed DNA methylations in 4.135 sites that were unique for the subgroup. Epigenetic markers associated with this subgroup could predict a lower risk of developing heart attack, stroke, and kidney disease. 

MARD (Mild age-related diabetes)
MARD is characterised by late-onset diabetes and relatively good metabolic control. MARD showed DNA methylations in 200 sites that were unique for this group. Epigenetic markers associated with this subgroup could predict an increased risk of developing heart attack, stroke, and kidney disease. 
 

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). 

Photograph of researcher.

Contact

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

 

Facts about the study

Research subject: Type 2 diabetes, epigenetics
Research area: Clinical research, epidemiological research 
Publication: Peer reviewed publication
Study design: Quantitative study
Experimental investigation: In vitro, in vivo 
Observational study (epidemiological): Prospective, cohort study (All new diabetics in Skåne – Andis – and All New Diabetics in Uppsala – Andiu)
Number of groups in the study: 4
Number of patients in the study: 553

Link to the study in Diabetes Care

Funding

The study was supported by grants from European diabetes foundation (EFSD), Swedish Heart Lung Foundation, the Novo Nordisk Foundation, the Swedish Research Council, Region Skåne (ALF), European Research Council (Paintbox), H2020-Marie Skłodowska-Curie grant agreement no 706081 (EpiHope), Swedish Research Council (EXODIAB: Excellence of diabetes research in Sweden), Swedish Foundation for Strategic Research (LUDC-IRC) and Swedish Diabetes Foundation.