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Epigenetic Mechanisms (© pigurdesign/DIfE)

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Status: 18.11.2019 20:45:04

New Marker Provides Insights into the Development of Type 2 Diabetes

Press release 05.11.2018

Small chemical changes in the DNA building blocks, which may be influenceable by lifestyle factors, can reduce the amount of IGFBP2. A DIfE / DZD research team has now reported in the journal Diabetes that these epigenetic changes increase the risk of type 2 diabetes. Moreover, people with high blood levels of the binding protein IGFBP2 are less likely to develop this metabolic disorder. The changes in the blood are already detectable a few years prior to the onset of the disease.

According to the German Diabetes Health Report 2018, more than 5.7 million people in Germany suffer from type 2 diabetes. The affected individuals react inadequately to the hormone insulin, which leads to elevated blood glucose levels. This in turn can lead to strokes, heart attacks, retinal damage, kidney damage and nerve disorders. Since the metabolic disease develops gradually, initial damage has usually already occurred at the time of diagnosis. ”In the future, our findings may help to identify risk potentials for type 2 diabetes even earlier and help to counteract the disease with preventive measures," said Professor Annette Schürmann, head of the Department of Experimental Diabetology at the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) and speaker of the German Center for Diabetes Research (DZD).

Uncovering the molecular mechanisms

In addition to insulin, insulin-like growth factor 1 (IGF-1) is also involved in the metabolism of sugar and fat. The effect of this growth factor is weakened by binding to the IGF-binding protein 2 (IGFBP2). If the liver does not release enough IGFBP2 into the blood, the balance of the glucose and lipid metabolism may be disrupted. The research team led by Schürmann and Professor Matthias Schulze, head of the Department of Molecular Epidemiology at DIfE, therefore investigated how the diminished effect of the IGFBP2 gene could influence the development of type 2 diabetes.

Human studies show that people suffering from fatty liver produce and release less IGFBP2. Schürmann’s team observed similar effects in earlier mouse experiments, which showed that IGFBP2 levels were already reduced prior to the liver disease. This is due to the transfer of methyl groups at certain sites of the IGFBP2 DNA sequence, which inhibited the gene in the liver. These so-called epigenetic changes are caused, among other things, by lifestyle factors. Such modifications of the DNA in the IGFBP2 gene were also previously detected in blood cells of overweight people with impaired glucose tolerance.

Translational research from mouse to human studies

The interdisciplinary research team led by Schürmann and Schulze used findings from the clinic and laboratory to evaluate blood samples and data from the EPIC Potsdam Study. "This study is a good example of how translational research works: A clinical finding is taken up, analyzed mechanistically in the laboratory and finally examined in a population-wide study," said Schürmann.

Recent analyses by the researchers indicate that inhibition of the IGFBP2 gene promotes type 2 diabetes. In addition, the team of scientists observed that leaner study participants and study participants with lower liver fat levels had higher concentrations of the protective binding protein in the blood. Higher plasma concentrations of IGFBP2 were associated with a lower risk of developing type 2 diabetes in subsequent years. "Our study confirms the hypothesis that the IGF-1 signaling pathway also plays an important role in the development of type 2 diabetes in humans," added Dr. Clemens Wittenbecher, research associate in the Department of Molecular Epidemiology at DIfE and first author of the study.


Original Publication
Wittenbecher C, Ouni M, Kuxhaus O, Jähnert, M, Gottmann P, Teichmann, A, Meidtner, K, Kriebel, J, Grallert, H, Pischon, T, Boeing, H, Schulze, MB, Schürmann, A. Insulin-like growth factor binding protein 2 (IGFBP-2) and the risk of developing type 2 diabetes. Diabetes 2018

Related Articles
Kammel A, Saussenthaler S, Jähnert M, Jonas W, Stirm L, Hoeflich A, Staiger H, Fritsche A, Häring HU, Joost HG, Schürmann A, Schwenk RW. Early hypermethylation of hepatic Igfbp2 results in its reduced expression preceding fatty liver in mice. Human Molecular Genetics 2016

Baumeier C, Saussenthaler S, Kammel A, Jähnert M, Schlüter L, Hesse D, Canouil M, Lobbens S, Caiazzo R, Raverdy V, Pattou F, Nilsson E, Pihlajamäki J, Ling C, Froguel P, Schürmann A, Schwenk RW. Hepatic DPP4 DNA Methylation Associates With Fatty Liver. Diabetes 2017

Schwenk RW, Jonas W, Ernst SB, Kammel A, Jähnert M, Schürmann A. Diet-dependent alterations of hepatic Scd1 expression are accompanied by differences in promoter methylation. Hormone and Metabolic Research 2013

Background Information

Epigenetics is a relatively young field of research. It investigates altered gene functions that are not attributable to a change in the DNA sequence, but can still be inherited. Recent studies have increasingly suggested that diet as an environmental factor can also have a lasting effect on the activity status of genes, e.g. by chemical (epigenetic) changes of the DNA building blocks. This also includes methylations. These arise when methyl groups bind to the DNA. This can either make the activation of the genes more difficult or easier. The direct methylation of DNA permanently changes gene expression when it occurs in control regions of genes (so-called CpG islands), which have been made accessible by the modification of histones.

EPIC Potsdam Study
The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study is a prospective cohort study. Between 1994 and 1998, 27,548 women and men between the ages of 35 and 65 were recruited. They completed questionnaires about their eating habits, lifestyle and health status. This survey was repeated approximately every 3 years. The EPIC Potsdam study is part of one of the largest long-term studies worldwide with a total of approximately 521,000 study participants from ten European countries. The aim is to investigate the influence of nutrition on the development of cancer and other chronic diseases.


Prof. Dr. Annette Schürmann
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Arthur-Scheunert-Allee 114-116
14558 Nuthetal/Germany
phone: +49 33200 88-2368

Dr. Clemens Wittenbecher
Department of Molecular Epidemiology
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Arthur-Scheunert-Allee 114-116
14558 Nuthetal/Germany
phone: +49 33200 88-2454

Media Contact:

Sonja Schäche
Head of Press and Public Relations
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Arthur-Scheunert-Allee 114-116
14558 Nuthetal/Germany
phone: +49 33200 88-2278

The German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) is a member of the Leibniz Association. It investigates the causes of nutrition-associated diseases in order to develop new strategies for prevention, treatment and nutritional recommendations. Its research interests include the cause and consequences of the metabolic syndrome, a combination of obesity, hypertension (high blood pressure), insulin resistance and lipid metabolism disorder, the role of nutrition for healthy aging and the biological bases of food choices and dietary behavior. DIfE is also a partner of the German Center for Diabetes Research (DZD), which has been funded by the German Federal Ministry of Education and Research (BMBF) since 2009.

The Leibniz Association connects 93 independent research institutions. Its focus ranges from the natural, engineering and environmental sciences to the economic, spatial and social sciences and the humanities. Leibniz Institutes are dedicated to socially, economically and ecologically relevant questions. They conduct knowledge- and application-oriented research, also in the collaborative Leibniz Research Alliances, provide or maintain scientific infrastructures and offer research-based services. The Leibniz Association focuses on knowledge transfer, especially with the Leibniz Research Museums. It advises and informs policy makers in government, academia, industry and the general public. Leibniz institutions maintain close cooperation with universities - e.g. in the form of the Leibniz Science Campi, with industry and other partners at home and abroad. They are subject to a transparent and independent assessment procedure. Due to their nationwide importance, the federal government and the states jointly support the institutes of the Leibniz Association. The Leibniz Institutes employ around 19,100 people, including 9,900 scientists. The total budget of the institutes is more than 1.9 billion euros.

The German Center for Diabetes Research (DZD) is one of six German Centers of Health Research. It brings together experts in the field of diabetes research and combines basic research, epidemiology and clinical applications. By adopting an innovative, integrative approach to research, the DZD aims to make a substantial contribution to the successful, personalized prevention, diagnosis and treatment of diabetes mellitus. The members of the association are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center Düsseldorf (DDZ), the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Zentrum München at the University of Tübingen, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of TU Dresden, associated partners at the universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich, and other project partners.


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