Potsdam-Rehbruecke/Berlin – A research team led by Anna Floegel of the German Institute of Human Nutrition (DIfE) and Tobias Pischon of the Max Delbrueck Center for Molecular Medicine (MDC) has identified 14 novel biomarkers for type 2 diabetes. They can serve as basis for developing new methods of treatment and prevention of this metabolic disease. The biomarkers can also be used to determine diabetes risk at a very early point in time. At the same time the markers enable insight into the complex mechanisms of this disease, which still have not been completely elucidated. (Diabetes, A. Floegel et al., 2012; DOI 10.2337/db12-0495)*.
The researchers studied the blood of study participants from three different studies with respect to their metabolites (metabolomics). The study was based on data and blood samples of the prospective EPIC-Potsdam** study with more than 27,500 study participants, the Tuebingen family study and the KORA study***. The study was conducted in collaboration with the German Center for Diabetes Research (DZD) and funded by the Federal Ministry of Education and Research (BMBF).
Metabolomics is still a young research field and serves the understanding of biological systems. It studies the dynamic network of metabolites of an organism and thus provides insight into ongoing biochemical processes. Metabolites have quite diverse functions. For instance, they play a role in cellular communication and regulation, transport energy or are building material for the cells. Changes in metabolite concentrations may therefore directly reflect alterations in metabolism and thereby, shed light on the pathogenesis or presence of disease.
The aim of the current study was to identify metabolites in blood which provide insight into the pathomechanisms of type 2 diabetes and in addition can be used as biomarkers to determine the disease risk. To this end, the researchers studied a total of 4,000 blood samples. About 3,000 of these samples came from the EPIC-Potsdam study, nearly 900 samples from the KORA study in Augsburg and 76 from the study in Tuebingen. At the time the blood sample was taken, none of the study participants suffered from type 2 diabetes: However, during the average follow-up time of seven years, 800 Potsdam study participants and 91 Augsburg participants were diagnosed with type 2 diabetes. The 76 participants in the Tuebingen study were already classified at the beginning of the study as individuals at high risk for type 2 diabetes. At the time the blood sample was taken, however, they were still healthy.
163 metabolites analyzed per blood sample Jerzy Adamski and his team at the Institute of Experimental Genetics of Helmholtz Zentrum Muenchen analyzed the concentrations of 163 metabolites per blood sample. Fourteen of these metabolites exhibited a strong association with the development of type 2 diabetes.
"In addition to simple sugars, the 14 identified metabolites include various protein components and choline-containing phospholipids which play a role in the structure of cell membranes and in the transport of blood lipids," said Anna Floegel, lead author of the study. "Our findings particularly indicate a previously unknown role of phospholipids in type 2 diabetes development. This is a first clue which should definitely be pursued."
"At the same time the metabolites can also be used as biomarkers to precisely determine the risk of diabetes at a very early stage, since the study is based on prospective data, that is data that were collected before the onset of the disease," said Tobias Pischon, who led the study. "The results of the new metabolomic analysis thus provide a good basis for developing new treatment and prevention methods."
*Identification of Serum Metabolites Associated with Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
Anna Floegel1*; Norbert Stefan2; Zhonghao Yu3; Kristin Mühlenbruch4; Dagmar Drogan1; Hans-Georg Joost5; Andreas Fritsche2; Hans-Ulrich Häring2; Martin Hrabě de Angelis6; Annette Peters7; Michael Roden8,9; Cornelia Prehn6; Rui Wang-Sattler3; Thomas Illig3,10; Matthias B. Schulze4; Jerzy Adamski6; Heiner Boeing1; and Tobias Pischon1,11.
From the 1Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; the 2Department of Internal Medicine IV, Divisions of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany; the 3Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany; the 4Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; the 5Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; the 6Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany; the 7Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany; the 8Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Duesseldorf, Germany; the 9Department of Metabolic Diseases, University Clinics, Duesseldorf, Germany; the 10Hannover Unified Biobank, Hannover Medical School, Hannover, Germany; the 11Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany
** EPIC stands for European Prospective Investigation into Cancer and Nutrition. It is one of the largest prospective studies investigating the relationships between diet, cancer and other chronic diseases such as type 2 diabetes. Ten European countries with a total of 519,000 female and male adult test subjects are participating in the EPIC study. In Germany the German Cancer Research Center (DKFZ) in Heidelberg and the DIfE are part of the multicenter study. The EPIC-Potsdam study led by Heiner Boeing includes more than 27,500 adult study participants.
When evaluating a prospective study it is important that at the beginning of the study the participants do not yet have the disease under investigation. Thus, the risk factors for a given disease can be detected before disease onset, thus preventing as far as possible a distortion of the data by the disease– a decisive advantage over retrospective studies.
For information on the EPIC-Potsdam Study see also: http://www.dife.de//forschung/projekte/epic.php,
For information on the Tuebingen Family Study, see also: http://www.med.uni-tuebingen.de/Forschung/Kliniken/Medizinische+Klinik/Innere+Medizin+IV.html
For information on the Augsburg KORA Study, see also: http://www.helmholtz-muenchen.de/kora/.
The MDC combines basic research in molecular biology with clinical research. Building on insights gained from research, the aim of the MDC is to develop new and more effective strategies for the diagnosis and treatment of serious diseases and to explore possibilities for preventing their onset. The research activities of the MDC focus on cardiovascular research, metabolic diseases, cancer and diseases of the nervous system. The MDC is one of 18 research centers of the Helmholtz Association, the largest research organization in Germany and is financed to 90 percent by the federal government and to 10 percent by the state of Berlin.
The Helmholtz Association makes its contribution to solving major and urgent challenges faced by society, science and industry by undertaking top-flight scientific research in six research areas: energy, earth and environment, health, key technologies, structure of matter, aeronautics, space and transport. The Helmholtz Association is the largest science organization in Germany with a staff of 31,745 in 18 research centers and an annual budget of around EUR 3.4 billion. Its work follows the tradition of the great natural scientist Hermann von Helmholtz (1821-1894). (http://www.helmholtz.de/)
The DIfE is a member of the Leibniz Association. It explores the causes of nutrition-related diseases to develop new strategies for prevention, treatment and dietary recommendations. The research interests of the DIfE are obesity, diabetes, cardiovascular diseases and cancer. More at http://www.dife.de. The DIfE is also a partner of the DZD, which was founded in 2009 and is funded by the Federal Ministry of Education and Research. More at http://www.dzd-ev.de.
The Leibniz Association comprises 86 institutions conducting application-oriented basic research and providing scientific infrastructure. In total, around 16,800 people work for Leibniz institutions – including 7,800 scientists and researchers – with an annual budget of nearly EUR 1.4 billion. The Leibniz Association is characterized by the diversity of research topics and disciplines in which it is engaged. The research museums of the Leibniz Association preserve and explore the natural and cultural heritage. They are also the showcase of research as well as places of learning and fascination for science. More at http://www.leibniz-gemeinschaft.de.
Professor Tobias Pischon
Molecular Epidemiology Research Group
Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch
Phone: +49 (0)30/ 9406 - 4563
Head of the Press Department
Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10, 13125 Berlin
Phone: +49 (0)30/ 9406 - 3896
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Department of Epidemiology
German Institute of Human Nutrition
14558 Nuthetal/ Germany
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Dr. Gisela Olias
Head of Press and Public Relations
German Institute of Human Nutrition
Phone: +49 (0)33200/ 88 – 2278; - 2335
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