Pre-diabetes subtypes identified

All prediabetes are not the same: in people in the preliminary stages of type 2 diabetes, there are six clearly distinguishable subtypes, which differ in the development of the disease, risk of diabetes and the development of secondary diseases. This is shown in a study by the Helmholtz Zentrum München Institute for Diabetes and Metabolic Diseases Research (IDM); at the University of Tübingen, University Hospital of Tübingen; and the German Diabetes Research Center (DZD). The results have already been published in Nature Medicine. The new classification may help in the future to prevent the onset of diabetes or the development of diabetes complications through targeted prevention.

Diabetes is a worldwide pandemic. Since 1980, the number of people with diabetes has quadrupled worldwide. In Germany alone, 7 million people suffer from this. And the trend is still growing. By 2040, the number of people with type 2 diabetes may increase to as many as 12 million. But type 2 diabetes does not develop overnight. People often go through a longer preliminary stage of diabetes, in which blood glucose levels are already high, but people are not yet sick. “For people with pre-diabetes, it has not been possible until now to predict whether they would develop diabetes and be at risk of serious complications, such as kidney failure, or if they would only have a harmless form with slightly higher blood glucose levels, but without significant risk “said Professor Hans-Ulrich Häring, who started the study 25 years ago.

However, this distinction is important for the targeted prevention of metabolic disease and, therefore, for combating the diabetes pandemic. The Tübingen researchers have now achieved an important breakthrough. Using cluster analysis in people with pre-diabetes, they found six distinct subtypes with different diabetes risks. A different classification of pre-diabetes and diabetes allows the prevention and individual and early therapy of diabetes and its secondary diseases to be adapted to the development of the disease.

The research group led by Professor Häring and Professor Fritsche of the University Hospital in Tübingen conducted detailed studies of the metabolism of people with pre-diabetes who are still considered healthy. The test persons (n ​​= 899) are from the Tübingen Family Study and from the Tübingen Lifestyle Program study. They have been subjected to intensive clinical examinations, laboratory chemicals, MRI and genetic tests 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 pre-diabetes subtypes. “As with overt diabetes, there are also different types of diseases in the preliminary stage of diabetes, which differ in blood glucose levels, insulin action and secretion, body fat distribution, liver fat and genetic risk,” said the first author, Professor Robert Wagner, from the DZD Institute for Research on Diabetes and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, summarizing the results of the study.

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

But can the classification into six pre-diabetes subtypes also be confirmed in other cohorts? To investigate this, the researchers extended the analysis to include almost 7,000 individuals at Whitehall II Cohort in London and there, too, identified the six pre-diabetes subtypes.

Researchers are already making new plans. “Next, in prospective studies, we will first seek to determine the extent to which the new findings are applicable to the classification of individual persons at risk groups,” said Professor Andreas Fritsche, from Tübingen University Hospital. In this case, people with a high risk profile can be identified early and receive specific treatment.

These results are based on research conducted by the Diabetes Research Department at Tübingen University Hospital over the past 25 years to characterize people at increased risk of 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 goals of DZD is to develop precise prevention and therapy measures, that is, prevention or adequate treatment for the right group of people at the right time. The combination of in-depth molecular and clinical research with the state of the art has made bioinformatics This internationally important result is possible. The identification of subtypes in the preliminary stages of type 2 diabetes is an important step for precision medicine in the prevention of diabetes and its complications “, said the Executive Director of DZD, Prof. Martin Hrabě de Angelis.

Supplied by Deutsches Zentrum fuer Diabetesforschung DZD