Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes Byung-Soo Youn, 1,2 Nora Klo ¨ ting, 3 Ju ¨ rgen Kratzsch, 4 Namseok Lee, 1 Ji Woo Park, 1 Eun-Sun Song, 1 Karen Ruschke, 3 Andreas Oberbach, 3 Mathias Fasshauer, 3 Michael Stumvoll, 3 and Matthias Blu ¨ her 3 OBJECTIVE—Vaspin was identified as an adipokine with insu- lin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. How- ever, the regulation of vaspin serum concentrations in human obesity and type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS—For the measurement of vaspin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating vaspin in a cross-sectional study of 187 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes before and after a 4-week physical training program. RESULTS—Vaspin serum concentrations were significantly higher in female compared with male subjects. There was no difference in circulating vaspin between individuals with NGT and type 2 diabetes. In the normal glucose-tolerant group, circulating vaspin significantly correlated with BMI and insulin sensitivity. Moreover, physical training for 4 weeks resulted in significantly increased circulating vaspin levels. CONCLUSIONS—We found a sexual dimorphism in circulating vaspin. Elevated vaspin serum concentrations are associated with obesity and impaired insulin sensitivity, whereas type 2 diabetes seems to abrogate the correlation between increased circulating vaspin, higher body weight, and decreased insulin sensitivity. Low circulating vaspin correlates with a high fitness level, whereas physical training in untrained individuals causes increased vaspin serum concentrations. Diabetes 57:372–377, 2008 R ecently, visceral adipose tissue– derived serpin (vaspin) was identified as a member of serine protease inhibitor family, which was expressed in visceral adipose tissue of Otsuka Long-Evans Tokushima fatty (OLETF) rats at the age when obesity and insulin plasma concentrations reach a peak (1). Vaspin expression was shown to decrease with worsening of diabetes and body weight loss, whereas vaspin serum levels could be normalized by insulin or pioglitazone treatment. Administration of vaspin to obese mice im- proved glucose tolerance, insulin sensitivity, and altered gene expression of candidate genes for insulin resistance (1). We have recently demonstrated that human vaspin mRNA expression in adipose tissue of obese subjects is fat depot specific but not detectable in lean normal glucose- tolerant individuals (2). We postulated that induction of vaspin mRNA expression in human adipose tissue could represent a compensatory mechanism associated with obesity, severe insulin resistance, and type 2 diabetes (2,3). Taken together, these studies demonstrate that the adipokine vaspin is a novel candidate to link human obesity to its related metabolic alterations. Until now, no data are available for the regulation of human circulating vaspin. It is unknown whether circu- lating vaspin is related to measures of obesity, insulin sensitivity, and glucose metabolism. We therefore devel- oped an enzyme-linked immumnosorbent assay (ELISA) for the measurement of human vaspin serum concentra- tions. To this end, a human vaspin–specific monoclonal antibody was generated, which was then utilized to create a sandwich ELISA. Using this new vaspin ELISA, we sought to determine circulating vaspin in individuals with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance. In addition, we assessed vaspin serum concentration before and after an intensive 4-week physical training program to test whether vaspin levels are regulated in response to training-associated improvements in body weight and insulin sensitivity. RESEARCH DESIGN AND METHODS Cross-sectional study. A total of 187 Caucasian men (n = 89) and women (n = 98) were selected among 700 subjects recruited in the context of a study on insulin resistance at the Department of Medicine, University of Leipzig, to represent a wide range of obesity, insulin sensitivity, and glucose tolerance. The age ranged from 17 to 79 years and BMI from 19.6 to 61.5 kg/m 2 . Subjects were subsequently divided into groups of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes on the basis of a 75-g oral glucose tolerance test (OGTT) according to American Diabetes Association criteria (4). Subjects with NGT were defined by a fasting plasma glucose 6.0 mmol/l and a 120-min plasma glucose 7.8 mmol/l. Subjects with IGT were defined by a fasting plasma glucose 6.0mmol/l and a 120-min plasma glucose 7.8 and 11.1 mmol/l. Subjects with type 2 diabetes were From 1 AdipoGen, College of Life Science and Biotechnology, Korea Univer- sity, Seoul, Korea; the 2 Immunomodulation Research Center, University of Ulsan, Ulsan, Korea; the 3 Department of Medicine, University of Leipzig, Leipzig, Germany; and the 4 Institute of Clinical Chemistry and Pathobiochem- istry, University of Leipzig, Leipzig, Germany. Address correspondence and reprint requests to Matthias Blu ¨ her, MD, University of Leipzig, Department of Medicine, Ph.-Rosenthal-Str. 27, 04103 Leipzig, Germany. E-mail: bluma@medizin.uni-leipzig.de; or Byung S. Youn, PhD, Scientific Director, AdipoGen. E-mail: bsyoun@adipogen.com. Received for publication 28 July 2007 and accepted in revised form 3 November 2007. Published ahead of print at http://diabetes.diabetesjournals.org on 8 Novem- ber 2007. DOI: 10.2337/db07-1045. Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1045. B.-S.Y. and N.K. contributed equally to this work. ELISA, enzyme-linked immunosorbent assay; HEK, human embryonic kid- ney; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; PAI-1, plasminogen activator inhibitor type 1. © 2008 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. ORIGINAL ARTICLE 372 DIABETES, VOL. 57, FEBRUARY 2008