We only begin to understand diabetes

Around 10% of people develop diabetes worldwide, in some Asian countries such as India, it‘s up to 20%. The numbers are increasing. Even after so many years studying the disease, we just begin to understand the underlying cause. Leif Groop, MD, PhD is one of the most successful diabetes researchers in the world. Since 1993, he is a professor at Lund University, Sweden and research director at the Finnish Institute for Molecular Medicine, FIMM, at Helsinki University where he focuses on the genetics and metabolism of diabetes. He recently realized a major breakthrough by defining five diabetes subclasses, which is the first step towards personalized diabetes treatment. He discovered his passion for unlocking diabetes secrets during his very first job as a doctor in Närpes.

Fascinated by diabetes research

Prof Leif Groop is intrigued by the importance and the challenge of diabetes research. Groop’s interest in diabetes started already during his very first job back in the seventies. He worked as a doctor in a clinic in Närpes, a small town in the west of Finland. Diabetes care was very bad in Närpes, and a consultant wrote nasty comments about how poorly they were treating diabetes patients. Groop could not stand this accusation. Soon after, he received a stipend, and he used this opportunity to prove that he could do better. He joined a diabetes care centre in Sweden, in Dalby, near Lund and committed himself to improving diabetes care dramatically. 

Groop’s primary research interest lies in the genetics of diabetes. “Heredity plays an essential role in the development of some diabetes subgroups. I realized this  more than 20 years ago, back in 1992, long before modern genetic tools evolved. I put a lot of time and effort into better understanding the genetic cause of the condition, but most of it did not pay off. I was often told that my work was a waste of time. I continued because he I couldn’t believe that this was the end of it”, tells Groop. Luckily! Today we have a much better understanding of the disease. His discoveries paved the way towards individualized diabetes treatment and precision medicine.

Misclassification of diabetes subtypes

For many years, there has been a misclassification of type 1 and type 2 diabetes. Groop’s main accomplishment is the discovery of five subgroups, which allows a more individualized therapy. “There is a large group of type 2 diabetes patients that all receive a very similar standard treatment. I realized that patients in this group actually fall into five different clusters, which we defined as subgroups 1 to 5. Cluster 4 and 5 are two mild forms of diabetes, and they differ mainly in the body weight and age of disease onset. Patients in group 5 are older than patients in group 4 who are very obese. Group 3 is characterized by strong insulin resistance, but only mildly elevated glucose levels. This group is also associated with an increased risk of developing kidney and fatty liver disease. Treatment for group 3 should focus on improving insulin sensitivity rather than lowering glucose. The earlier patients are classified into the correct subgroup, the earlier they will receive optimal treatment that can potentially modify the course of the disease. Especially patients that belong to cluster 3 are likely to benefit from this discovery”, explains Groop.

Do we understand what diabetes is?

“Not really. It’s a grey mass that includes different diseases. We only begin to understand the underlying cause”. We know that diabetes comprises a group of metabolic disorders that have one feature in common: elevated blood glucose levels. There is, however, a variety of underlying causes. In the groups that Groop classifies as cluster 1 and 2, patients suffer from an insulin deficiency and as a result cannot control their glucose levels without exogenous insulin. Group 2 also has the highest risk of developing diabetic eye disease. Patients in group 3 have severe insulin resistance, and Group 4 and 5 have only mild metabolic disturbances. “It is essential to understand that not all subgroups have the same cause. Only an individualized approach to better understand the different underlying problems will allow us to control the disease efficiently”, according to Groop.

Will we be able to end diabetes soon?

“I hope so. It is a combination of prevention and treatment. Diabetes can only be cured if we address the five subclasses individually. There are three severe forms, if we identify them early, we can start individual treatment early on”, he said. “Stem cell therapy offers hope for curing type 1 diabetes. Type 1 diabetes is an autoimmune disease in which autoantibodies attack and destroy insulin-producing beta cells. The idea behind stem cell therapy is to replace beta cells. There is huge progress already in developing beta cell lines. In a few years, we can start injecting them into patients. They would get enough insulin, not needing to receive external insulin any longer.” For other subgroups, prevention is key. Prof. Groop is convinced that following a certain lifestyle is crucial in preventing type 4 and 5. “Go jogging in the morning, pay attention to what you eat, eat less, avoid too much sugar and carbohydrates.” To simplify early diagnosis and to assign patients to specific clusters, the group is developing an app. Simple parameters such as age, BMI, the presence of autoantibodies against beta cells and measurements to assess the patient’s insulin secretion and sensitivity are entered into the app, which will give an answer about which subclass the patient belongs to. The first version of the app was launched in summer 2018.

What’s next?

Leif Groop is not resting on his recent accomplishments and already started working on the next big project. He aims to identify gene variants that protect against diabetes. This stands in contrast to conventional approaches that instead look for variants that cause diabetes. “The idea is to target these favourable variants with drugs, which may decrease the chances of developing diabetes or improve an already existing diabetes condition”, concludes Groop. As he already proofed in the past: Extraordinary approaches lead to a meaningful outcome!