Relation of Plasma Fatty Acid Binding Proteins 4 and 5 With the Metabolic Syndrome, Inflammation and Coronary Calcium in Patients With Type-2 Diabetes Mellitus

被引:62
作者
Bagheri, Roshanak [1 ]
Qasim, Atif N. [1 ]
Mehta, Nehal N. [1 ]
Terembula, Karen [1 ]
Kapoor, Shiv [4 ]
Braunstein, Seth [2 ]
Schutta, Mark [2 ]
Iqbal, Nayyar [2 ]
Lehrke, Michael [4 ]
Reilly, Muredach P. [1 ,2 ,3 ]
机构
[1] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA
[4] Univ Munich, Dept Internal Med 2, Munich, Germany
关键词
INSULIN-RESISTANCE; ARTERY-DISEASE; APOLIPOPROTEIN-E; DEFICIENT MICE; ATHEROSCLEROSIS; AP2; OBESITY; RISK; CALCIFICATION; PREDICTION;
D O I
10.1016/j.amjcard.2010.06.028
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fatty acid binding proteins (FABPs) 4 and 5 play coordinated roles in rodent models of inflammation, insulin resistance, and atherosclerosis, but little is known of their role in human disease. The aim of this study was to examine the hypothesis that plasma adipocyte and macrophage FABP4 and FABP5 levels would provide additive value in the association with metabolic and inflammatory risk factors for cardiovascular disease as well as subclinical atherosclerosis. Using the Penn Diabetes Heart Study (PDHS; n = 806), cross-sectional analysis of FABP4 and FABP5 levels with metabolic and inflammatory parameters and with coronary artery calcium, a measure of subclinical coronary atherosclerosis, was performed. FABP4 and FABP5 levels had strong independent associations with the metabolic syndrome (for a 1-SD change in FABP levels, odds ratio [OR] 1.85, 95% confidence interval [CI] 1.43 to 2.23, and OR 1.66, 95% CI 1.41 to 1.95, respectively) but had differential associations with metabolic syndrome components. FABP4 and FABP5 were also independently associated with C-reactive protein and interleukin-6 levels. FABP4 (OR 1.26, 95% CI 1.05 to 1.52) but not FABP5 (OR 1.13, 95% CI 0.97 to 1.32) was associated with the presence of coronary artery calcium. An integrated score combining FABP4 and FABP5 quartile data had even stronger associations with the metabolic syndrome, C-reactive protein, interleukin-6, and coronary artery calcium compared to either FABP alone. In conclusion, this study provides evidence for an additive relation of FABP4 and FABP5 with the metabolic syndrome, inflammatory cardiovascular disease risk factors, and coronary atherosclerosis in type 2 diabetes mellitus. These findings suggest that FABP4 and FABP5 may represent mediators of and biomarkers for metabolic and cardiovascular disease in type 2 diabetes mellitus. (C) 2010 Published by Elsevier Inc. (Am J Cardiol 2010; 106:1118-1123)
引用
收藏
页码:1118 / 1123
页数:6
相关论文
共 27 条
[1]   QUANTIFICATION OF CORONARY-ARTERY CALCIUM USING ULTRAFAST COMPUTED-TOMOGRAPHY [J].
AGATSTON, AS ;
JANOWITZ, WR ;
HILDNER, FJ ;
ZUSMER, NR ;
VIAMONTE, M ;
DETRANO, R .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1990, 15 (04) :827-832
[2]  
Grundy Scott M, 2005, Crit Pathw Cardiol, V4, P198
[3]   Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice [J].
Boord, JB ;
Maeda, K ;
Makowski, L ;
Babaev, VR ;
Fazio, S ;
Linton, MF ;
Hotamisligil, GS .
CIRCULATION, 2004, 110 (11) :1492-1498
[4]   Coronary Calcium Predicts Events Better With Absolute Calcium Scores Than Age-Sex-Race/Ethnicity Percentiles MESA (Multi-Ethnic Study of Atherosclerosis) [J].
Budoff, Matthew J. ;
Nasir, Khurram ;
McClelland, Robyn L. ;
Detrano, Robert ;
Wong, Nathan ;
Blumenthal, Roger S. ;
Kondos, George ;
Kronmal, Richard A. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2009, 53 (04) :345-352
[5]   Plasma fatty acid-binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria [J].
Cabre, Anna ;
Lazaro, Iolanda ;
Girona, Josefa ;
Manzanares, Josep M. ;
Marimon, Francesc ;
Plana, Nuria ;
Heras, Mercedes ;
Masana, Lluis .
CLINICAL CHEMISTRY, 2008, 54 (01) :181-187
[6]   Regulation of metabolic responses by adipocyte/macrophage fatty acid-binding proteins in leptin-deficient mice [J].
Cao, Haiming ;
Maeda, Kazuhisa ;
Gorgun, Cem Z. ;
Kim, Hyo-Jeong ;
Park, So-Young ;
Shulman, Gerald I. ;
Kim, Jason K. ;
Hotamisligil, Gokhan S. .
DIABETES, 2006, 55 (07) :1915-1922
[7]   Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study [J].
Elkeles, Robert S. ;
Godsland, Ian F. ;
Feher, Michael D. ;
Rubens, Michael B. ;
Roughton, Michael ;
Nugara, Fiona ;
Humphries, Steve E. ;
Richmond, William ;
Flather, Marcus D. .
EUROPEAN HEART JOURNAL, 2008, 29 (18) :2244-2251
[8]   Adipocyte/macrophage fatty acid binding proteins in metabolic syndrome [J].
Erbay E. ;
Cao H. ;
Hotamisligil G.S. .
Current Atherosclerosis Reports, 2007, 9 (3) :222-229
[9]   Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice [J].
Furuhashi, Masato ;
Fucho, Raquel ;
Gorgun, Cem Z. ;
Tuncman, Guerol ;
Cao, Haiming ;
Hotamisligil, Goekhan S. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2640-2650
[10]   Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2 [J].
Furuhashi, Masato ;
Tuncman, Guerol ;
Goerguen, Cem Z. ;
Makowski, Liza ;
Atsumi, Genichi ;
Vaillancourt, Eric ;
Kono, Keita ;
Babaev, Vladimir R. ;
Fazio, Sergio ;
Linton, MacRae F. ;
Sulsky, Richard ;
Robl, Jeffrey A. ;
Parker, Rex A. ;
Hotamisligil, Goekhan S. .
NATURE, 2007, 447 (7147) :959-U2