Journal Article

α2-Heremans-Schmid Glycoprotein/ Fetuin-A Is Associated With Insulin Resistance and Fat Accumulation in the Liver in Humans

Anita M. Hennige, Stefan M. Kröber, Hans-Ulrich Häring, Norbert Stefan, Andreas Fritsche, Fausto Machicao, Harald Staiger, Jürgen Machann, Fritz Schick

2006

Overview

α 2 -Heremans-Schmid Glycoprotein/ Fetuin-A Is Associated With Insulin Resistance and Fat Accumulation in the Liver in Humans Norbert Stefan , MD 1 , Anita M. Hennige , MD 1 , Harald Staiger , PHD 1 , Jürgen Machann , PHD 2 , Fritz Schick , PHD 2 , Stefan M. Kröber , MD 3 , Fausto Machicao , PHD 1 , Andreas Fritsche , MD 1 and Hans-Ulrich Häring , MD 1 1 Department of Internal Medicine, University of Tübingen, Tübingen, Germany 2 Section on Experimental Radiology, University of Tübingen, Tübingen, Germany 3 Department of Pathology, University of Tübingen, Tübingen, Germany Address correspondence and reprint requests to Norbert Stefan, MD, Department of Internal Medicine, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. E-mail: norbert.stefan{at}med.uni-tuebingen.de Abstract OBJECTIVE —The α 2 -Heremans-Schmid glycoprotein (AHSG; fetuin-A in animals) impairs insulin signaling in vitro and in rodents. Whether AHSG is associated with insulin resistance in humans is under investigation. In an animal model of diet-induced obesity that is commonly associated with hepatic steatosis, an increase in Ahsg mRNA expression was observed in the liver. Therefore, we hypothesized that the AHSG plasma protein, which is exclusively secreted by the liver in humans, may not only be associated with insulin resistance but also with fat accumulation in the liver. RESEARCH DESIGN AND METHODS —Data from 106 healthy Caucasians without type 2 diabetes were included in cross-sectional analyses. A subgroup of 47 individuals had data from a longitudinal study. Insulin sensitivity was measured by a euglycemic-hyperinsulinemic clamp, and liver fat was determined by 1 H magnetic resonance spectroscopy. RESULTS —AHSG plasma levels, adjusted for age, sex, and percentage of body fat, were higher in subjects with impaired glucose tolerance compared with subjects with normal glucose tolerance ( P = 0.006). AHSG plasma levels were negatively associated with insulin sensitivity ( r = −0.22, P = 0.03) in cross-sectional analyses. Moreover, they were positively associated with liver fat ( r = 0.27, P = 0.01). In longitudinal analyses, under weight loss, a decrease in liver fat was accompanied by a decrease in AHSG plasma concentrations. Furthermore, high AHSG levels at baseline predicted less increase in insulin sensitivity ( P = 0.02). CONCLUSIONS —We found that high AHSG plasma levels are associated with insulin resistance in humans. Moreover, AHSG plasma levels are elevated in subjects with fat accumulation in the liver. This is consistent with a potential role of AHSG as a link between fatty liver and insulin resistance. AHSG, α2-Heremans-Schmid glycoprotein Footnotes Additional information on this article can be found in an online appendix at http://care.diabetesjournals.org . A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted January 2, 2006. Received October 11, 2005. DIABETES CARE

• Publisher: American Diabetes Association
• Subject: Biological and medical sciences / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Gastroenterology. Liver. Pancreas. Abdomen / Liver. Biliary tract. Portal circulation. Exocrine pancreas / Medical sciences / Other diseases. Semiology