Proteins can be used to predict prediabetes - Patent from the KORA study

A team of DZD researchers has developed a new method of predicting the early stages of type 2 diabetes mellitus. Their findings, published in the journal Diabetologia, show that the presence of certain proteins in blood plasma may hold the vital clue to the development of the disease.

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, a partner in the DZD, 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and searched for a total of 23 proteins that they had selected based on literature mining and their own, previously unpublished results.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.

Further Information
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.

Original publication:
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