People with type 1 diabetes and type 2 diabetes are often crudely diagnosed but more and more research indicate that diabetes is more complex than that. In 2018, researchers at LUDC published a study that showed that type 1 diabetes and type 2 diabetes could be classified into five subgroups. These subgroups are based on disease progression and what the risk of developing common diabetes-related complications looks like for each group.
A more recent study by the same researchers from 2021 has shown that there are also distinct genetic differences between the four subgroups pertaining to type 2 diabetes. The study is based on data from 10,000 recently diagnosed persons with diabetes from the population study ANDIS (All new diabetics in Skåne).
“Our research shows there are distinct genetic differences between the groups, which in turn means that the causes of type 2 diabetes vary somewhat”, says Emma Ahlqvist, researcher in genomics, diabetes, and endocrinology at LUDC and one of the main authors of the study published in Nature Genetics.
Differences between people with diabetes
A lot of people with type 2 diabetes need insulin drug therapy. For some, it takes several years before they need to start taking insulin, while for others it may be necessary already at the time of diagnosis. Researchers are trying to understand why these differences exist and the study of subgroups may provide clues. One of the subgroups, for example, has proven to be very different to other groups of people with type 2 diabetes. The disease group SIRD (severe insulin-resistant diabetes) includes people who are overweight, suffer a high degree of insulin resistance, and are at higher risk of developing kidney disease.
“This is a group of people who usually have good insulin production but instead have problems with insulin sensitivity. They may have a lot of insulin in the blood and may need treatment to increase insulin sensitivity so that the insulin has desired effect”, says Emma Ahlqvist.
In two of the other subgroups, insulin production is impaired. These subgroups are SAID (severe autoimmune diabetes) and SIDD (severe insulin-deficient diabetes), and for people in these groups it may be necessary to start insulin treatment at an earlier stage. The researchers hope that genetic data about the different subgroups can be useful when tailoring the treatment of people with diabetes.
“First, we need to see clear evidence that individualised treatments give good results in clinical studies. We also need studies that investigate how our classification can be applied to different ethnic groups”, she says.
The importance of lifestyle
We inherit our genes, and they rarely change. However, type 2 diabetes is often associated with lifestyle factors and therefore, it is not enough to just study the genes to understand the disease. Epigenetics (see fact box) give researchers new opportunities to understand the reasons behind type 2 diabetes.
Charlotte Ling, professor of epigenetics at Lund University, has done research in this field for many years and is one of the authors of a review paper in Nature Reviews Endocrinology that summarises the most important advances.
“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, head of a research group at LUDC.
Epigenetic biomarkers
Lifestyle factors like excess weight, unhealthy foods, sedentary living, and aging can lead to substantial epigenetic changes in healthy people. More and more research indicate that these factors contribute to the development of type 2 diabetes.
DNA methylation is an example of an epigenetic change that means that chemical compounds attach to the genes and affect their function. Several studies from researchers at Lund University have identified altered DNA methylation in the pancreas, adipose tissue, skeletal muscles, and liver in individuals with type 2 diabetes. In the future, epigenetic biomarkers may become an important tool when providing individualised treatments.
Charlotte Ling’s research group has discovered epigenetic biomarkers that help them understand who will benefit from the drug metformin. Metformin is a common drug for the treatment of type 2 diabetes and for many, it lowers blood sugar levels. However, not everyone responds to the treatment and those who don’t risk elevated blood sugar levels and drug-related side effects.
“There is growing awareness within 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.
In her research group there is also ongoing work to develop epigenetic biomarkers that can predict which people with type 2 diabetes are at an increased risk of developing common diabetes complications, such as stroke, myocardial infarction, and kidney disease. The research builds on previous research at LUDC that shows that there are distinct genetic differences between different subgroups of type 2 diabetes. Charlotte Ling highlights the importance of epigenetics and genetics working together.
“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”, she says.
This article was produced as part of a digital theme on precision medicine by Vetenskap & hälsa.
