Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans.
OBJECTIVE
The alpha(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.


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.
Stefan
Norbert
N
Department of Internal Medicine, University of Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de
Hennige
Anita M
AM
Staiger
Harald
H
Machann
Jürgen
J
Schick
Fritz
F
Kröber
Stefan M
SM
Machicao
Fausto
F
Fritsche
Andreas
A
Häring
Hans-Ulrich
HU
D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D001786:Blood Glucose; D001798:Blood Proteins / Q000032:analysis*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D016014:Linear Models; D008099:Liver / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D015431:Weight Loss; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001786:Blood Glucose; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein