Type 2 diabetes and cardiovascular disease are preceded by metabolic alterations. A current study by the DZD and DIfE indicates that specific lipid molecules (ceramides*), which are produced when the body metabolizes fats, are involved in the development of type 2 diabetes and cardiovascular diseases. The study also establishes a link between an unhealthy diet and unfavorable ceramide levels in the blood. This could explain, for example, why the risk of diabetes increases with frequent consumption of red and processed meat. As potential biomarkers, ceramides could enable more precise dietary approaches for the prevention of cardiometabolic diseases. The results of the study have now been published in ‘Nature Communications’.

Unhealthy dietary habits can contribute to the development of heart attack, stroke and type 2 diabetes (cardiometabolic diseases). However, it is not yet known exactly which biochemical processes underlie this. State-of-the-art high-throughput techniques make it possible to simultaneously assess a large number of metabolites in the blood and thus provide comprehensive metabolic profiles in large study groups. This shows that specific lipid molecules, ceramides and dihydroceramides, could be critical factors for long-term cardiometabolic health. Furthermore, diet influences the composition of ceramides and dihydroceramides.  

Comprehensive studies on the influence of diet on ceramide levels in the blood and possible effects on the development of cardiometabolic diseases in humans have so far been lacking. The researchers therefore observed several thousand participants in the EPIC-Potsdam study** over a period of several years in order to assess whether the occurrence of cardiometabolic diseases can be predicted on the basis of specific ceramides influenced by diet. The study was conducted under the leadership of the German Institute of Human Nutrition (DIfE) and supported by the German Center for Diabetes Research (DZD) and the BMBF-funded project "FAME "***. The study results show that ceramide profiles provide insights into the development of cardiometabolic diseases and can improve the understanding of the influence of diet on disease risk. 

Ceramide profiling
At the beginning of the study, all participants provided information about their diet and blood samples. None of the participants had type 2 diabetes or cardiovascular disease. In the following years, about 550 subjects developed cardiovascular disease and nearly 800 developed type 2 diabetes. Using a novel analytical platform called lipidomics, the researchers profiled the ceramides and dihydroceramides in the blood of the EPIC-Potsdam participants. 

Specific ceramides mediate adverse effects of unhealthy eating
The researchers then investigated whether disease-relevant ceramides and dihydroceramides are also linked to food consumption. "People who eat a lot of meat have a higher risk of diabetes. We have now shown for the first time that high consumption of red and processed meat was associated with unfavorable levels of diabetes-related ceramides. Our results suggest that the association between meat consumption and diabetes risk may be mediated by the influence on ceramide levels in the blood," said first author Clemens Wittenbecher, a member of the Department of Molecular Epidemiology at DIfE and the Harvard T.H. Chan School of Public Health. Matthias Schulze, head of the Department of Molecular Epidemiology at DIfE and last author of the study added: "Detailed metabolic profiles in large cohort studies help us to better understand the relationship between diet and disease risk. This ultimately contributes to evidence-based and more accurate dietary recommendations."  

Study opens up new prevention approaches
Cardiometabolic diseases such as heart attack, stroke and type 2 diabetes account for more than one-third of deaths worldwide. The results of the current study identified specific ceramides as potential biomarkers for the relationship between diet and disease risk, and thus could enable more precise nutritional approaches for the prevention of cardiometabolic diseases.  

Original publication: 
Wittenbecher, C. … Schulze, M. et al: Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology. Nature Communications (2022) DOI: doi.org/10.1038/s41467-022-28496-1

* Ceramides are a subgroup of sphingolipids that are important components of cell membranes and act as signaling molecules. They influence various metabolic processes, including insulin sensitivity and inflammatory responses. Ceramides may be involved in the pathogenesis of type 2 diabetes and cardiovascular disease.

** The EPIC-Potsdam study is a population-based prospective cohort study and part of the international EPIC study. It includes around 27,500 participants. At the start of the study in 1994, the women were 35 to 64 years old and the men were 40 to 64 years old. With its extensive database, the EPIC-Potsdam study serves as the basis for population-based epidemiological research at the DIfE. The research results help to create the scientific basis for possible preventive measures and to improve the health of the population. https://www.dife.de/forschung/kooperationen/epic-studie/ 

*** The collaborative project FAME ("Fatty Acid Metabolism: Interlinking Diet with Cardiometabolic Health") was funded by the German Federal Ministry of Education and Research (BMBF) as part of the European Joint Programme Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL). In this initiative, EU member states, associated states, as well as Canada and New Zealand are working together to pool and strengthen nutrition research across national borders. The aim of the transnational funding measure "Biomarkers for Nutrition and Health" of the JPI HDHL is to identify new biomarkers that can detect nutritional status and thus contribute to elucidating the relationships between nutrition and health. In addition to DIfE, the universities of Navarra and Cordoba (Spain) as well as Reading and East Anglia (UK) are involved in the FAME network.  https://fame.dife.de/ 

German Institute of Human Nutrition Potsdam-Rehbruecke 
The DIfE is a member of the Leibniz Association. It investigates the causes of diet-related diseases in order to develop new strategies for prevention and therapy and to provide dietary recommendations. Its research focus includes the causes and consequences of the metabolic syndrome, which is a combination of obesity, high blood pressure, insulin resistance and lipid metabolism disorder, as well as the role of diet in healthy aging and the biological basis of food choices and eating habits. In addition, DIfE is a partner of the German Center for Diabetes Research (DZD), which was founded in 2009 and has since been funded by the BMBF.