Researchers Discover New Indicator for Insulin Resistance in Humans

High concentrations of free fatty acids (FFAs) in the blood predict insulin resistance in humans only when high blood concentrations of the fatty liver protein fetuin-A are present at the same time. This finding was published by Professor Norbert Stefan of the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Zentrum München at the University of Tübingen, a partner in the DZD, in the current issue of "Nature Medicine".


Interaction between fatty acids in the blood with the glycoprotein fetuin-A, which is secreted by a fatty liver, may possibly be the common basis for the pathogenesis of widespread diseases such as type 2 diabetes, cardiovascular disease and certain types of cancer.
Type 2 diabetes, cardiovascular disease and certain types of cancer often occur concomitantly. The decreased insulin activity in the body that is associated with subclinical inflammation is viewed as a very important common cause. For many years, elevated fatty acid concentrations in the blood have been under suspicion as the primary culprit. However, the available data in humans was not very robust.
Norbert Stefan, Heisenberg Professor for Clinical-Experimental Diabetology, and his research team at Tübingen University Hospital have now found that fatty acid concentrations in the blood in humans can only predict insulin resistance if concomitantly high concentrations of the fatty liver protein fetuin-A are present. Their findings expand knowledge on this question, which was first addressed in a study on mice. Professor Stefan and Professor Hans-Ulrich Häring of Tübingen University Hospital report their new findings in the current issue of Nature Medicine.

Blood parameters indicate risk groups
Based on data from 347 healthy subjects who are at increased risk for type 2 diabetes, the researchers were able to show that the blood concentrations of free fatty acid interact with the concentrations of the protein fetuin-A, indicating that this interaction is a predictor for insulin resistance. As a control, the researchers investigated whether such relationships might also be present for circulating concentrations of adiponectin, but no such interaction with the fatty acids could be shown. “Thus, on the basis of these blood parameters, we can identify subgroups of people who have a very high risk for insulin resistance,” Stefan said. “Our data also provide a basis for a rapid analysis of several thousand patients within the scope of large-scale studies to determine how important these findings are for the development of type 2 diabetes, cardiovascular diseases and certain types of cancer.”
With these new findings, the Tübingen researchers directly build on their successful and innovative research on the role of the fatty liver in the pathogenesis of these diseases. For example, already this year they could elucidate the significance of different fatty liver proteins, including fetuin-A. The new findings confirm that fetuin-A needs the fatty acids for its pathogenic properties with regard to metabolic diseases. Further studies in cooperation with the DZD on this topic are planned.

Title of the publication
Stefan N, Häring HU. Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nat Med. 2013 Apr 19(4):394-5. doi: 10.1038/nm.3116.