Diagnosing Type 2 diabetes at an early stage with new biomarkers

Focus on sugar and sugar compounds

Around the world, 463 million adults live with diabetes mellitus. Some 90 percent of them suffer from type 2 diabetes which, unlike type 1, is largely caused by lifestyle. Around half of cases are not diagnosed at an early stage; due to the insidious development of the disease they often remain undetected over a long period. At the Max Rubner-Institut’s Department of Safety and Quality of Fruit and Vegetables, an analytical tool has been developed for the analysis of sugar compounds and their derivatives. In a study involving healthy, pre-diabetic and diabetic participants, this analytical tool revealed previously unknown sugar compounds in the blood which changed in relation to the diabetic status of participants. Thus, they may be able to serve as biomarkers for improved, early diagnosis.

Diagnosing type 2 diabetes at an early stage means preventive measures, such as a change in diet and more exercise, can be introduced to prevent the onset of the disease and even cure early stages of type 2 diabetes. Blood sugar levels, glucose in urine and glycated haemoglobin (HbA1C) in the blood are good markers for diagnosing the disease and monitoring its progress. But markers that produce a diagnosis even earlier, fast, easily, and safely before symptoms have appeared would be preferable.

In recent years, so-called metabolomics methods have increasingly been used to find new markers because they facilitate a comprehensive analysis of all the compounds to be found in urine or blood, for example. Metabolomics data therefore enable scientists to gain deeper insights into the metabolism and can help to improve understanding of disease development. Although diabetes is a disease that essentially affects the sugar metabolism, so far, very few sugars and sugar compounds have been identified as changing in the context of insulin resistance. Insulin resistance is one of the most important metabolic changes that occurs at the beginning of diabetic disease whereby the body becomes increasingly insensitive to insulin release in response to a high-sugar meal. One of the difficulties about searching for sugars as biomarkers are analytical problems because this substance class includes many very similar compounds that cannot easily be separated. Using a sophisticated analytical method, the Department of Safety and Quality of Fruit and Vegetables can now measure a variety of sugars and sugar compounds in biological samples. They are not only able to determine the presence of typical monosaccharides and disaccharides like glucose, fructose and sucrose but also their derivates, such as sugar alcohols, sugar acids and amino sugars as well as rare sugars.

The Max Rubner-Institut investigated the blood sugar profile of healthy, pre-diabetic and diabetic participants who had taken part in a human intervention study conducted at the Technical University of Munich (collaboration with Prof. Daniel’s and Prof. Skurk’s research group). In total, 40 different sugars and sugar compounds were found in the blood, of which 27 sugar compounds could be clearly identified whilst the remaining 13 compounds can, as yet, only be assigned to certain classes of sugar compounds. Rare and unusual sugar compounds in the blood like allulose, trehalose and xylonic acid were also identified.
The analysis revealed a clear difference between the fasting blood sugar profiles of healthy, pre-diabetic and diabetic participants: Not only in the case of the classic blood sugar, glucose, but also other sugars such as mannose, maltose, trehalose, fructose and 1,5-anhydrosorbitol showed significantly different amounts in the plasma of diabetic participants in comparison with healthy participants. Furthermore, it was also demonstrated that there are sugar compounds like allulose and another as yet unidentified sugar compound that increase after administering the test drink, irrespective of the participants’ diabetic status. Other compounds (including trehalose, mannose, fructose, threitol) exhibited similar time-dependent changes in concentrations to glucose after receiving the test drink. It is still unclear how this is linked to the insulin metabolism. But the results deriving from fasting plasma and the oral glucose tolerance test clearly reveal how little is known so far about the metabolism of the “other” often unreported and thus overlooked sugars.

Given the characteristic differences between some sugars and sugar compounds in healthy, pre-diabetic and diabetic participants it would seem to be worthwhile to investigate their effectiveness as early markers of type 2 diabetes.