Pre-diabetes subtypes identified

Not all prediabetes are the same: in people in the first stage of type 2 diabetes, there are six subtypes that are clearly distinguishable, which differ in the development of the disease, diabetes risk and the development of secondary diseases. This emerges from a study by the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München; at the University of Tübingen, the Tübingen University Hospital; and the German Center for Diabetes Research (DZD). The results are now in Physical Medicine. The new classification may help in the future to prevent the manifestation of diabetes or the development of diabetes complications through targeted prevention.

Diabetes is a global pandemic. Since 1980, the number of people with diabetes worldwide has tripled. In Germany alone, 7 million people suffer from it. And the trend is still increasing. By 2040, the number of people with type 2 diabetes could increase to as many as 12 million. But type 2 diabetes does not develop from one day to the next. People often go through a longer preliminary stage of diabetes, in which blood glucose levels have already been raised but people are not yet ill. “Until now, for people with prediabetes, it was not possible to predict whether they would develop diabetes and be at risk for serious complications such as kidney failure, or that they would only have a harmless form with slightly higher blood glucose levels, but without significant risk., “said Professor Hans-Ulrich Häring, who began the study 25 years ago.

However, such a distinction is important for the purposeful prevention of the metabolic disease and thus to counteract the diabetes pandemic. Researchers from Tübingen have now achieved an important breakthrough. Using group analysis in people with prediabetes, they discovered six different subtypes with different diabetes risks. A differentiated classification of prediabetes and diabetes makes it possible to carry out individual and early prevention and therapy of diabetes and its secondary diseases in a way adapted to the development of the disease.

The research group led by Professor Häring and Professor Fritsche at the University Hospital in Tübingen conducted detailed studies on the metabolism of people with prediabetes who are still considered healthy. The test subjects (n = 899) come from the Tübingen family study and the study of the Tübingen lifestyle program. They have repeatedly undergone intensive clinical, laboratory chemical, magnetic resonance imaging and genetic research in Tübingen over the past 25 years.

Based on important metabolic parameters such as blood glucose levels, liver fat, body fat distribution, blood lipid levels, and genetic risk, the researchers were able to identify six subtypes of prediabetes. “As in manifest diabetes, there are also different types of diseases in the preliminary stage of diabetes, which differ in blood glucose levels, insulin action and insulin secretion, distribution of body fat, liver fat and genetic risk,” said the first author, Professor Robert Wagner of the DZD Institute for Diabetes Research and Metabolic Diseases (IDM) from Helmholtz Zentrum München at the University of Tübingen, summarizing the results of the study.

Three of these groups (groups 1, 2 and 4) are characterized by a low risk of diabetes. The study participants in groups 1 and 2 were healthy. Slim people are the main members of group 2. They have a particularly low risk of developing complications. Cluster 4 consists of overweight people whose metabolism is still relatively healthy. The three remaining subtypes (groups 3, 5 and 6) are associated with an increased risk of diabetes and / or secondary diseases. People who are part of subtype 3 produce too little insulin and are at high risk of developing diabetes. People in group 5 have a pronounced fatty liver and a very high risk of diabetes because they are resistant to the blood glucose lowering effect of insulin. In subtype 6, damage to the kidneys occurs even before diabetes is diagnosed. Mortality is also particularly high here.

But can the classification into six subtypes of prediabetes be confirmed in other groups as well? To investigate this, the researchers expanded the analysis to nearly 7,000 subjects in the Whitehall II group in London, and also identified the six subtypes of prediabetes.

The researchers are already making further plans. “Next, in prospective studies, we will first try to determine the extent to which the new findings apply to the division of individuals into risk groups,” said Professor Andreas Fritsche of Tübingen University. If this is the case, people with a high risk profile can be identified early and receive specific treatment.

These results are based on research conducted over the past 25 years by the Department of Diabetes Research at Tübingen University Hospital to identify people at increased risk for diabetes. The study was funded by the German Research Foundation, the Federal Ministry of Education and Research and the State of Baden-Württemberg.

“One of the objectives of the DZD is to develop precise prevention and therapy measures, ie the appropriate prevention or treatment for the right group of people at the right time. The combination of in-depth clinical and molecular research with the latest bioinformatics technology has made this international “The identification of subtypes in the preliminary stages of type 2 diabetes is an important step towards precision medicine in the prevention of diabetes and its complications,” says prof. Martin Hrabě de Angelis, DZD CEO.

Provided by Deutsches Zentrum fuer Diabetesforschung DZD