The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels Samad Akbarzadeh a , Iraj Nabipour a,⇑ , Majid Assadi b , Ali Movahed a , Seyed Mojtaba Jafari a , Niloofar Motamed a , Habibollah Nazem c , Mehrnoosh Haraghy a , Abdolreza Pourbehi c , Afshar Bargahi d , Najmeh Hajian a a Department of Endocrine and Metabolic Diseases, The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514763448, Iran b Department of Hormones, The Persian Gulf Nuclear Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514763448, Iran c Department of Biochemistry, Tehran Payame Noor University, Tehran 7514763448, Iran d Department of Biochemistry, The Persian Gulf Marine Biotechnology Research Center, Bushehr University of Medical Sciences, Bushehr 7514763448, Iran article info Article history: Received 4 July 2011 Received in revised form 28 November 2011 Accepted 7 February 2012 Available online 6 March 2012 Keywords: Diabetes mellitus Adipocytokines Omentin-1 Adiponectin Retinol-binding protein 4 abstract Objective: It has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimet- ics and some others may induce insulin resistance. In order to elucidate the potential role of novel adi- pocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). Method: Serum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme- linked immunosorbent assay (ELISA) methods. Results: There was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06–11.52] ng/ml versus 10.50 [4.30– 20.60] ng/ml, p = 0.004) and adiponectin (mean ± SD, 10.07 ± 4.0 lg/ml versus 20.66 ± 8.12 lg/ml, p < 0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponec- tin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR = 0.49, CI [0.30–0.79]; p = 0.004 and OR = 0.74, CI [0.67–0.82]; p < 0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. Conclusions: The FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs’ increased risk of diabetes needs to be further elucidated. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction It has been suggested that adipose-derived cytokines act as a potential link between energy homeostasis, immunity, neuroendo- crine, atherosclerosis, type 2 diabetes, and insulin resistance [1–4]. Several of these bioactive mediators that are collectively called ‘adipocytokines’ may be considered insulin sensitizers/insulin- mimetics, and some others may induce insulin resistance [5]. Omentin-1 is a novel 34 kDa adipokine that is highly and selec- tively expressed in visceral adipose tissue compared with subcuta- neous adipose tissue [6,7]. Furthermore, omentin-1 enhances insulin action and Akt phosphorylation [7]; it is inversely related to obesity [8] and is down regulated by insulin and glucose [9]. Adiponectin is the most abundant adipocytokine with insulin sensitizing, anti-inflammatory, and anti-atherogenic effects [1,4]. Adiponectin levels have inverse correlations with dyslipidemia, atherosclerosis, glucose intolerance, and insulin resistance in diverse patient populations [1,3]. In fact, hypoadiponectinemia has been suggested as one of the most important adipocytokines in the pathogenesis of type 2 diabetes [1]. The serum levels of retinol-binding protein 4 (RBP-4) reflect the risks of impaired glucose tolerance and type 2 diabetes [10]. The link between elevated RBP-4 levels and impaired insulin secre- tion has been shown in insulin resistant humans with obesity, impaired glucose tolerance and type 2 diabetes, and even in lean 1043-4666/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.cyto.2012.02.005 Abbreviations: FDRs, first-degree relatives of subjects with type 2 diabetes mellitus; RBP4, retinol-binding protein 4; ELISA, enzyme-linked immunosorbent assay; BMI, body mass index; OGTT, oral glucose tolerance test; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HOMA-IR, homeostasis model of assess- ment index; CV, coefficient of variance; WHR, waist to hip ratio. ⇑ Corresponding author. Address: The Persian Gulf Tropical Medicine Research Center, Boostan 19 Alley, Imam Khomeini St., Bushehr, Iran. Tel.: +98 7712541827; fax: +98 7712541828. E-mail address: inabipour@gmail.com (I. Nabipour). Cytokine 58 (2012) 295–299 Contents lists available at SciVerse ScienceDirect Cytokine journal homepage: www.elsevier.com/locate/issn/10434666