Associations of fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy.
BACKGROUND
Ambigous results exist on fetuin-A as marker for vascular disease in type 2 diabetes. This study aims to define the role of fetuin-A as marker for micro- and macrovascular disease in a high risk population of patients with type 2 diabetes mellitus and early diabetic nephropathy.


METHODS
Fetuin-A serum levels were assessed by ELISA in a cross-sectional setting in 153 patients with type 2 diabetes. Associations of fetuin-A with metabolic, inflammatory and vascular markers were studied. Atherosclerotic burden was assessed by ankle-brachial-index (ABI) as well as detection of common carotid artery intima-media thickness (IMT).


RESULTS
Levels of fetuin-A were lower in male than in female patients (0.49 ± 0.15 vs. 0.56 ± 0.20 g/L, p = 0.02). In addition, there was an inverse correlation with age (r = -0.20, P = 0.01). Bivariate correlations adjusted for age and gender revealed no significant correlations with metabolic parameters, except for a weak inverse correlation with serum adiponectin (r = -0.19, p = 0.02). Regarding parameters of micro- and macrovascular disease, fetuin-A was significantly associated with ABI (r = 0.18, p = 0.04), while there was no association with IMT (r = -0.07, p = n.s). Patients with an ABI < 0.9 had lower fetuin A levels than patients with an ABI 0.9-1.3 or > 1.3 (0.43 ± 0.10 vs. 0.52 ± 0.17 vs. 0.54 ± 0.18 g/L p = 0.05). Neither GFR nor albuminuria were associated with fetuin-A serum levels. Patients with prevalent neuropathy did not have altered fetuin-A levels compared to diabetic controls. In step-wise logistic regression analysis including age, gender, HbA1c, total cholesterol, glomerular filtration rate and fetuin-A, only total cholesterol (β = 0.01, p = 0.02) and fetuin-A (β = -5.99, p = 0.03) proved to be independent predictors of an ABI < 0.9.


CONCLUSIONS
The results of this cross-sectional study suggest that lower fetuin-A levels are associated with macrovascular late complications in high-risk type 2 diabetes patients while there are no associations of fetuin-A with metabolic status or microvascular complications.
Roos
Marcel
M
Department of Nephrology, Klinikum rechts der Isar, Munich, Germany. marcel.roos@lrz.tum.de
Oikonomou
Dimitrios
D
von Eynatten
Maximilian
M
Luppa
Peter B
PB
Heemann
Uwe
U
Lutz
Jens
J
Baumann
Marcus
M
Nawroth
Peter P
PP
Bierhaus
Angelika
A
Humpert
Per M
PM
D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D015415:Biomarkers; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein
J Biol Chem. 2003 Apr 11;278(15):13333-41
12556469
Clin Chem. 2007 Apr;53(4):766-72
17332152
Eur Heart J. 2008 May;29(10):1307-15
18390868
Diabetes Care. 2005 Sep;28(9):2201-5
16123490
PLoS One. 2008 Mar 12;3(3):e1765
18335040
Circulation. 2008 Dec 9;118(24):2555-62
19029462
Horm Metab Res. 2007 Dec;39(12):899-902
18046662
Kidney Int. 2005 Mar;67(3):1070-7
15698447
Metabolism. 2010 Jun;59(6):873-8
20015522
Kidney Int. 2007 Jul;72(2):202-7
17342178
Am J Cardiol. 2007 Feb 19;99(4A):80B-88B
17307060
Eur J Clin Invest. 2010 Feb;40(2):95-102
19912308
Diabetes Care. 2005 Jan;28(1):164-76
15616252
Diabetes. 2008 Oct;57(10):2762-7
18633113
Atherosclerosis. 2009 Dec;207(2):341-2
19615685
J Am Soc Nephrol. 2005 Nov;16(11):3357-64
16177000
N Engl J Med. 2004 Apr 1;350(14):1387-97
15070788
Diabetes Care. 2010 Feb;33(2):408-10
19910501
Am J Cardiol. 2010 Jun 15;105(12):1666-72
20538112
Arch Intern Med. 2006 Jul 10;166(13):1368-73
16832001
Nature. 1997 Mar 6;386(6620):78-81
9052783
Cardiovasc Diabetol. 2009 Aug 06;8:45
19660101
Diabetes Care. 2010 Apr;33(4):e55; author reply e56
20351222
Cardiovasc Diabetol. 2005 Mar 18;4:4
15777477
J Am Coll Cardiol. 2010 May 11;55(19):2080-91
20447530
Lancet. 2003 Mar 8;361(9360):827-33
12642050
Coron Artery Dis. 2010 Aug;21(5):281-5
20436350
JAMA. 2008 Jul 9;300(2):182-8
18612115
J Clin Invest. 2003 Aug;112(3):357-66
12897203
N Engl J Med. 2008 May 15;358(20):2107-16
18480203
Circulation. 2006 Apr 11;113(14):1760-7
16567568