HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stefan, N. Articles by Häring, H.-U. Search for Related Content PubMed PubMed Citation Articles by Stefan, N. Articles by Häring, H.-U. Social Bookmarking                What's this?

₂-Heremans-Schmid Glycoprotein/ Fetuin-A Is Associated With Insulin Resistance and Fat Accumulation in the Liver in Humans

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

OBJECTIVE—The 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 ¹H 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.

Abbreviations: AHSG, ₂-Heremans-Schmid glycoprotein

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Stefan, K. Kantartzis, J. Machann, F. Schick, C. Thamer, K. Rittig, B. Balletshofer, F. Machicao, A. Fritsche, and H.-U. Haring Identification and Characterization of Metabolically Benign Obesity in Humans Arch Intern Med, August 11, 2008; 168(15): 1609 - 1616. [Abstract] [Full Text] [PDF]

				J. H. Ix, C. L. Wassel, A. M. Kanaya, E. Vittinghoff, K. C. Johnson, A. Koster, J. A. Cauley, T. B. Harris, S. R. Cummings, M. G. Shlipak, et al. Fetuin-A and Incident Diabetes Mellitus in Older Persons JAMA, July 9, 2008; 300(2): 182 - 188. [Abstract] [Full Text] [PDF]

				G. Andersen, K. S. Burgdorf, T. Sparso, K. Borch-Johnsen, T. Jorgensen, T. Hansen, and O. Pedersen AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia: Studies of Metabolic Traits in 7,683 White Danish Subjects Diabetes, May 1, 2008; 57(5): 1427 - 1432. [Abstract] [Full Text] [PDF]

				J. Koska, N. Stefan, P. A Permana, C. Weyer, M. Sonoda, C. Bogardus, S. R Smith, D. R Joanisse, T. Funahashi, J. Krakoff, et al. Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals Am. J. Clinical Nutrition, February 1, 2008; 87(2): 295 - 302. [Abstract] [Full Text] [PDF]

				A. Kotronen and H. Yki-Jarvinen Fatty Liver: A Novel Component of the Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 27 - 38. [Abstract] [Full Text] [PDF]

				N. Stefan, A. M. Hennige, H. Staiger, J. Machann, F. Schick, E. Schleicher, A. Fritsche, and H.-U. Haring High Circulating Retinol-Binding Protein 4 Is Associated With Elevated Liver Fat but Not With Total, Subcutaneous, Visceral, or Intramyocellular Fat in Humans Diabetes Care, May 1, 2007; 30(5): 1173 - 1178. [Abstract] [Full Text] [PDF]