Plasma Fatty Acid-Binding Protein 4 Increases with Renal Dysfunction in Type 2 Diabetic Patients without Microalbuminuria Anna Cabre ´ , Iolanda La ´ zaro, Josefa Girona, Josep M. Manzanares, Francesc Marimo ´ n, Nu ´ ria Plana, Mercedes Heras, and Lluı ´s Masana * BACKGROUND: Fatty acid– binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evalu- ated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. METHODS: In 263 individuals (161 type 2 diabetic pa- tients and 102 healthy nondiabetic controls), we ana- lyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR 30 mL/min/1.73 m 2 ) or albuminuria were not included. RESULTS: FABP4 concentrations were higher in dia- betic patients with MDRD-GFR 60 mL/min/1.73 m 2 (P 0.001). We observed a significant, direct corre- lation between FABP4 and creatinine (r = 0.446, P 0.001) and an inverse correlation between FABP4 and MDRD-GFR (r =-0.511, P 0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those pa- tients without microalbuminuria were analyzed (r = 0.414, P 0.001 and r =-0.510, P 0.001, respec- tively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8 –30.7), P = 0.005 and 15.3 (3.1–76.4), P = 0.001; respectively], independent of microalbuminuria. CONCLUSIONS: High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consider- ation as an early marker of kidney damage in patients with type 2 diabetes. © 2007 American Association for Clinical Chemistry It is becoming increasingly evident that several mole- cules derived from adipose tissue are not only asso- ciated with adiposity and inflammation, but are also involved in the development of insulin resistance. Among them, some members of the lipocalin family— retinol-binding protein 4 (RBP4), 2 lipocalin-2, and fatty acid-binding protein 4 (FABP4)— have been sug- gested to play important roles in the mechanisms of insulin resistance. They have been proposed as early markers for adiposity associated with metabolic syn- drome (1–5 ). FABP4 is produced by adipocytes and macrophages during their differentiation and intra- cellular lipid accumulation (6 –10 ). Its main role seems to be intracellular fatty acid transport. Recently, our group and others have communicated that FABP4 plasma concentrations correlate to metabolic syn- drome components in diabetic and nondiabetic indi- viduals (3, 4, 6, 11 ). Furthermore, plasma FABP4 is considered an early marker of metabolic risk for meta- bolic syndrome development (11 ). Although FABP4 concentrations seem to be associated with adiposity, other factors such as inflammation status could also influence its concentrations (6). Our group has ob- served that FABP4 plasma concentrations in type 2 diabetic patients are also associated with high triglyc- erides, increased lipid peroxidation, and inflamma- tion markers (6); however, the role of FABP4 in target organ damage has not been fully assessed. The pres- 1 Research Unit on Lipids and Atherosclerosis, Faculty of Medicine and Health Sciences, IRCIS, Department of Internal Medicine, Saint Joan University Hospi- tal, Reus, Spain. * Address correspondence to this author at: Unitat de Recerca de Lı ´pids i Arteriosclerosi, Facultat de Medicina i Cie ` ncies de la Salut, C. Sant Llorenc ¸, 21, 43201 Reus, Spain. Fax 34977759322; e-mail luis.masana@urv.cat. Received July 10, 2007; accepted October 24, 2007. Previously published online at DOI: 10.1373/clinchem.2007.094672 2 Nonstandard abbreviations: RBP4, retinol-binding protein 4; FABP4, fatty acid– binding protein 4; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; BMI, body mass index; OR, odds ratio. Clinical Chemistry 54:1 000 – 000 (2008) Endocrinology and Metabolism 1 http://www.clinchem.org/cgi/doi/10.1373/clinchem.2007.094672 The latest version is at Papers in Press. Published November 16, 2007 as doi:10.1373/clinchem.2007.094672 Copyright (C) 2007 by The American Association for Clinical Chemistry