Even before the onset of type 2 diabetes, the first preliminary stages appear, which indicate an increased risk. As has now been shown, there are clear differences in this prediabetes. Researchers have identified six clearly distinguishable subtypes of prediabetes, three of which are not dangerous, but three others significantly increase the risk of severe diabetes and secondary diseases. The scientists hope that knowledge of these subtypes and their detection could help in the future to treat those affected more specifically and prevent diabetes more effectively.
Diabetes is one of the major widespread diseases: since 1980, the number of people with type 2 diabetes has quadrupled worldwide. In Germany alone, around seven million people currently suffer from this so-called age diabetes. It is estimated that by 2040 the number of people affected could increase to up to twelve million people. In this disease, the pancreas usually produces enough insulin initially. However, this can no longer effectively lower blood sugar because the body cells have become insensitive to this hormone. As the disease progresses, the amount of insulin released from the pancreas also decreases. As a result, the blood sugar level rises abnormally, which in turn can lead to secondary diseases such as kidney damage, retinal diseases and cardiovascular diseases.
Are there differences in the pre-diabetes stage?
However, type 2 diabetes does not develop overnight. Affected people often go through a longer preliminary stage of diabetes, the so-called prediabetes, in which the blood sugar levels are already elevated, but people are not yet sick. Until now, however, it has been difficult to determine in advance whether and when such a prediabetes will develop into diabetes. “Up to now, it was not possible to predict in people with prediabetes whether they would develop diabetes and have the risk of serious secondary diseases such as kidney failure, or whether they would only have a harmless form of slightly higher blood sugar levels without any significant risk,” explains senior author Hans-Ulrich Häring from the Institute for Diabetes Research and Metabolic Diseases (IDM) from the Helmholtz Center Munich at the University of Tübingen.
To change this, the researchers evaluated data from a long-term study in Tübingen, in which almost 900 healthy participants with the first signs of prediabetes were medically examined over a period of 20 years. Metabolic parameters relevant for diabetes, such as blood sugar levels, liver fat, body fat distribution and blood fat levels, were regularly analyzed, and the genetic risk was also determined. The team around Häring and first author Robert Wagner from IDM used a cluster analysis to search for subgroups within the group of participants that have similarities in terms of their risk factors and metabolic characteristics.
Six subtypes identified
The researchers found what they were looking for: They identified six subtypes of prediabetes, each with clearly distinguishable characteristics. “As with overt diabetes, there are also different types of disease in the early stages of diabetes, which differ in terms of blood sugar levels, insulin action and insulin release, body fat distribution, liver fat and genetic risk,” says Wagner, summarizing the result. The scientists were also able to confirm these six subtypes in a supplementary long-term study with 7,000 participants in London. As more detailed analyzes showed, three of these subtypes (clusters 1, 2 and 4) are characterized by a low risk of diabetes. Cluster 2 mainly includes slim people. You have a particularly low risk of developing complications. Cluster 4 is made up of overweight people whose metabolism is still relatively healthy – they are therefore among the “healthy fat people”, as the researchers explain.
In contrast, the risk is significantly higher for the three other subtypes (clusters 3, 5 and 6). In people belonging to subtype 3, the pancreas already produces too little insulin, and they are genetically predisposed. People from cluster 5 have a pronounced fatty liver and a very high risk of diabetes because their body cells are already resistant to the blood sugar-lowering effect of insulin. In subtype 6, kidney damage occurs even before diabetes is diagnosed. Here the mortality is particularly high, as the scientists report. They hope that this knowledge can now help to prevent diabetes more specifically. “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 accompanying diseases,” says Martin Hrabe de Angelis from the German Center for Diabetes Research in Neuherberg.
Source: Robert Wagner (University of Tübingen) et al., Nature Medicine, doi: 10.1038 / s41591-020-1116-9