In two comprehensive studies, scientists from Helmholtz Zentrum Muenchen, Ludwig-Maximilians-Universitaet Muenchen and Technische Universitaet Muenchen discovered new associations of two major Type 2 diabetes risk genotypes and altered plasma concentrations of metabolic products. The "Virtual Institute Diabetes" joint research cooperation is thereby making an important contribution towards explaining the genetic and molecular basis of diabetes, The results have been published in the journals PLOS ONE and Metabolomics.
For these investigations, participants of the population-based cohort study KORA* carrying high-risk diabetes gene variants without having a diagnosed diabetes, as well as participants without an increased diabetes risk were recruited.
All study participants were subjected to a metabolic load. The nutritients, particularly sugars and fats, were administered either orally or intravenously. The scientists subsequently determined the concentrations of 163 metabolic products in blood samples from the participants. The teams headed by Prof. Dr. Thomas Illig (HMGU) and Dr. Harald Grallert (HMGU), Prof. Dr. Jochen Seißler (LMU), and Prof. Dr. Hans Hauner (TUM) and Dr. Helmut Laumen (TUM) were the first to supply a comprehensive characterisation of the metabolic performance in regard to the respective genotype.
It was observed that the concentrations of the recorded substances represent a particular metabolomic response pattern depending on the genotype. It was possible to verify specific metabolic effects, particularly for the TCF7L2 genotype, which is associated with an increased risk of type 2 diabetes. "We are aware of certain high-risk gene variants for type 2 diabetes. However, the causative mechanisms on the path to this disease are still largely unknown. With our results, we are helping to close the gap between disease-associated genes on the one hand and the development of diabetes on the other. A typically changed metabolic performance can supply early indications of diabetes", explain Simone Wahl from HMGU and Cornelia Then from LMU, first authors of the two publications.
The scientists are currently investigating metabolic responses in additional genotypes. The objective is to advance the fundamental research on the widespread disease diabetes and to contribute the acquired knowledge to the clinical cooperation groups that have developed from the VID in order to promote the knowledge transfer between the laboratory and clinical care of patients suffering from diabetes.
Further Information
*KORA (Kooperative Gesundheitsforschung in der Region Augsburg)
For more than 20 years, the research platform Cooperative Health Research in the Augsburg Region (KORA) has been collecting and analyzing data on the health of thousands of people living in the Augsburg region. The objective is to elucidate the effects of environmental factors, behavior and genes. KORA focuses on the development and course of chronic diseases, in particular myocardial infarction and diabetes mellitus. Risk factors are analyzed with regard to individual health behavior (e.g. smoking, diet, exercise), environmental factors (e.g. air pollution, noise) and genetics. From the perspective of health care research, questions regarding the utilization of health care resources and the cost of health care are also studied. <http://www.helmholtz-muenchen.de/kora>
Original publications:
Then, C. et al. (2013). Plasma metabolomics reveal alterations of sphingo- and glycerophospholipids levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146, PLOS ONE, doi:10.1371/journal.pone.0078430
Link to publication <http://dx.plos.org/10.1371/journal.pone.0078430>
Wahl, S. et al. (2013), Comparative analysis of plasma metabolomics response to metabolic challenge tests in healthy subjects and influence of the FTO obesity risk allele, Metabolomics, doi 10.1007/s11306-013-0586-x
Link to publication <http://link.springer.com/article/10.1007%2Fs11306-013-0586-x>
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,100 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members. <http://www.helmholtz-muenchen.de>
The German Center for Diabetes Research (DZD) brings together experts in the field of diabetes research and interlinks basic research, epidemiology and clinical applications. Members are the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition (DIfE) in Potsdam-Rehbrücke, Helmholtz Zentrum München – German Research Center for Environmental Health, the Paul Langerhans Institutes of the University Hospital Carl Gustav Carus in Dresden and the University of Tübingen, as well as the Gottfried Wilhelm Leibniz Association and the Helmholtz Association of German Research Centres. The objective of the DZD is to find answers to open questions in diabetes research by means of a novel, integrative research approach and to make a significant contribution to improving the prevention, diagnosis and treatment of diabetes mellitus. <http://www.dzd-ev.de>
As one of Europe's leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 14 percent of LMU's 50,000 students come from abroad, originating from 125 countries worldwide. The know-how and creativity of LMU's academics form the foundation of the University's outstanding research record. This is also reflected in LMU's designation of as a "university of excellence" in the context of the Excellence Initiative, a nationwide competition to promote top-level university research. <http://www.en.lmu.de>
Technische Universität München (TUM) is one of Europe's leading universities. It has roughly 500 professors, 10,000 academic and non-academic staff, and 35,000 students. It focuses on the engineering sciences, natural sciences, life sciences, medicine, and economic sciences. After winning numerous awards, it was selected as an "Excellence University" in 2006 and 2012 by the Science Council (Wissenschaftsrat) and the German Research Foundation (DFG). In both international and national rankings, TUM is rated as one of Germany's top universities and is dedicated to the ideal of a top-level research-oriented entrepreneurial university. The university's global presence includes offices in Beijing (China), Brussels (Belgium), Cairo (Egypt), Mumbai (India) and São Paulo (Brazil). The German Institute of Science and Technology (GIST - TUM Asia), founded in 2002 in Singapore, is the first research campus of a German university abroad. <http://www.tum.de>
Scientific contact
Dr. Harald Grallert, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Research Unit Molecular Epidemiology, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany - Phone: +49-89-3187-1195 - Email: <harald.grallert@helmholtz-muenchen.de>
Journal
PLoS ONE