Type 2 diabetes does not develop from one day to the next. Often patients progress through lengthy preliminary stages, during which initial metabolic alterations occur. A team of researchers led by Dr. Stefanie Hauck and Dr. Barbara Thorand, the respective heads of the Research Unit Protein Science and the Diabetes Epidemiology working group at the Helmholtz Zentrum München, has now succeeded in identifying specific proteins which serve as biomarkers for these processes, and which may also cause them.
The scientists examined a total of 439 randomly selected blood plasma samples obtained from men and women between the ages of 47 and 76 as part of the population-based KORA (Cooperative Health Research in the Region of Augsburg) study. For several years now, this cohort study, in which a large number of volunteers have participated, has examined the causes of widespread diseases such as type 2 diabetes and cardiovascular disease. In this instance, the scientists were able to refer to data from Augsburg residents who had undergone oral glucose tolerance testing between 2006 and 2008 in cooperation with the German Diabetes Center (DDZ) in Düsseldorf, another DZD partner, in order to identify previously undiscovered type 2 diabetes and its pre-stages.
New biomarkers revealed by mass spectrometry
The scientists subjected the samples to a special type of mass spectrometry known as Selected Reaction Monitoring (SRM-MS), and searched for a total of 23 proteins that they had selected based on literature mining and their own, previously unpublished results. “We were able to identify associations between four proteins and so-called prediabetes, which had hitherto not been described,” explain Dr. Christine von Toerne and Dr. Cornelia Huth, the two first authors of the study.*
According to the authors, this is the largest-ever proteomic study of type 2 diabetes based on mass spectrometry to be described. However, how exactly the proteins contribute to diabetes remains unclear, and this is a question that the authors plan to address in future studies.
Patent application pending
The scientists are confident that their observations will not just be of theoretical interest. For that reason, they have already applied for the respective patent. “In the long term, we plan to channel our results into the development of a kit for the early diagnosis of type 2 diabetes,” says research team leader Dr. Stefanie Hauck. To ensure that this development is founded on solid data, she and her team are currently examining the samples from a further 600 Augsburg residents obtained within the framework of the KORA study.
The study was supported by an internal funding program of Helmholtz Zentrum München which aims to enhance “translational and clinical projects”.
* Specifically, the researchers found that the proteins mannan-binding lectin serine peptidase 1 (MASP1), thrombospondin 1 (THBS1), glycosylphosphatidylinositol specific phospholipase D1 (GPLD1) and apolipoprotein A-IV (APOA4) correlated with the onset of prediabetes (positively or negatively). In particular, MASP1 showed highly significant effects.
Von Toerne, C. & Huth, C. et al. (2016). MASP1, THBS1, GPLD1, APOA4 – novel biomarkers associated with prediabetes: the KORA F4 study, Diabetologia, doi: 10.1007/s00125-016-4024-2
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.
The independent Research Unit Protein Science (PROT) investigates the composition of protein complexes and their integration into cellular processes and protein networks. One focus is the analysis of the interaction of genetic variance and environmental factors in neurodegenerative and metabolic diseases. The aim of this research is to identify biological systems and disease-associated disorders on a systemic level, thus contributing to a molecular understanding of diseases.
The Institute of Epidemiology II (EPI II) focuses on the assessment of environmental and lifestyle risk factors which jointly affect major chronic diseases such as diabetes, heart disease and mental health. Research builds on the unique resources of the KORA cohort, the KORA myocardial infarction registry, and the KORA aerosol measurement station. Aging-related phenotypes have been added to the KORA research portfolio within the frame of the Research Consortium KORA-Age. The institute’s contributions are specifically relevant for the population as modifiable personal risk factors are being researched that could be influenced by the individual or by improving legislation for the protection of public health.
For almost 30 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.
The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.