Atherosclerosis 189 (2006) 401–407 Adiponectin is a candidate marker of metabolic syndrome in obese children and adolescents Luisa Gilardini a,1 , Philip G. McTernan b,1 , Andrea Girola a , Nancy F. da Silva b , Luisella Alberti a , Sudhesh Kumar b , Cecilia Invitti a,∗ a Unit of Metabolic Diseases and Diabetes, Istituto Auxologico Italiano, Via Ariosto 13, 20145 Milan, Italy b Unit for Diabetes and Metabolism, Warwick Medical School, University of Warwick, CV2 2DX, UK Received 4 November 2005; received in revised form 20 December 2005; accepted 21 December 2005 Available online 25 January 2006 Abstract The aim of this study was to compare the use of several biomarkers to identify obese children and adolescents with increased metabolic risk. One hundred sixty-two Caucasian obese children and adolescents (41% males, 9–18 years old) referred to the Istituto Auxologico Italiano between 2003 and 2004 underwent an oral glucose tolerance test. Circulating levels of adiponectin (AD), plasminogen activator inhibitor 1 (PAI-1), interleukin 18 (IL-18), C-reactive protein (CRP), fibrinogen, uric acid, lipids and insulin were measured. Twenty five percent of obese children had the MS defined using World Health Organization-derived child specific criteria. MS subjects had significantly lower AD (p < 0.01) and higher log-PAI-1 (p < 0.001), uric acid (p < 0.0001), and IL-18 (p < 0.001). Subjects with AD levels ≤median value had a significantly increased risk of having the MS (p < 0.0001), as did subjects with uric acid and PAI-1 levels greater than the median. There was no increased risk with elevated IL-18, CRP, or fibrinogen. Hypoadiponectinemia was independently associated with the MS risk (p < 0.0001). In conclusion in obese children and adolescents AD is the best predictor of MS and thus of higher cardiovascular disease risk. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Obese children; Metabolic syndrome; Adiponectin; PAI-1; Uric acid 1. Introduction Over the past decade, childhood obesity has increased in a dramatic fashion with 20% of children in Europe now classified as overweight [1]. This development accompanies an increased number of young obese populations diagnosed with the metabolic syndrome (MS), which at present affects a quarter of overweight children and adolescents [2,3]. The features of the MS include insulin resistance, glucose intoler- ance, hypertension, dyslipidemia, and central obesity, all of which are risk factors for coronary heart disease and type 2 diabetes. Several new features, such as the increase of plas- minogen activator inhibitor 1 (PAI-1) and C-reactive protein ∗ Corresponding author. Tel.: +39 02 619112535; fax: +39 02 619112541. E-mail address: invitti@auxologico.it (C. Invitti). 1 These authors equally contributed to the study. (CRP) and decrease of adiponectin (AD), have been recently added to the syndrome, which is now considered a low-grade inflammatory state [4,5]. PAI-1 is produced by adipose tissue and AD exclusively by adipocytes. Adipocyte mRNA expression of AD and CRP are negatively correlated with one another, and circulating levels of PAI-1, AD, and CRP are associated with central adiposity [4,6,7]. This information suggests that the potential link between the MS, obesity, and inflammation is proba- bly related to a dysregulated adipocyte production of factors that participate in the production of a proinflammatory and prothrombotic state [4]. Increased PAI-1 levels have been associated with risk of thrombosis and fibrosis, and PAI-1 has been shown to have a direct effect in the development of insulin resistance and type 2 diabetes [8,9]. Another proin- flammatory cytokine, IL-18, has been detected in human vascular plaques and is probably involved in atherogenesis 0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2005.12.021