Low Serum Cartonectin/CTRP3 Concentrations in Newly Diagnosed Type 2 Diabetes Mellitus: In Vivo Regulation of Cartonectin by Glucose Bo Ban 1" , Bo Bai 2" , Manman Zhang 1,3 , Jiamiao Hu 4 , Manjunath Ramanjaneya 4 , Bee K. Tan 4,5 * " , Jing Chen 2,4 * " 1 Department of Endocrine and Metabolic Diseases, Jining Medical College Affiliated Hospital, Jining Medical University, Jining, Shandong, P.R. of China, 2 Neurobiology Institute, Jining Medical University, Jining, Shandong, P.R. of China, 3 School of Medicine, Shandong University, Jinan, Shandong, P.R. of China, 4 Warwick Medical School, University of Warwick, Coventry, West Midlands, United Kingdom, 5 Department of Obstetrics and Gynaecology, Birmingham Heartlands and Solihull Hospitals, Heart of England NHS Foundation Trust, Birmingham, West Midlands, United Kingdom Abstract Objectives: Cartonectin is a novel adipokine of the C1q complement/TNF-related protein (CTRP) superfamily, with glucose lowering effects, anti-inflammatory and cardio-protective properties. We sought to investigate circulating cartonectin concentrations in subjects with type 2 diabetes mellitus (T2DM) as well as age and BMI matched control subjects. We also examined the effects of a 2 hour 75 g oral glucose tolerance test (OGTT) on serum cartonectin concentrations in T2DM subjects. Design: Cross-sectional study [newly diagnosed (first discovery, not on any treatments) T2DM (n = 47) and control (n = 63) subjects]. Serum cartonectin was measured by ELISA. Results: Serum cartonectin concentrations were significantly lower in patients with T2DM compared to controls (P,0.05). Furthermore, serum cartonectin was significantly negatively correlated with glucose and CRP, and significantly positively correlated with leptin, in all subjects (n = 110). When subjected to multiple regression analysis, none of these variables were predictive of serum cartonectin (P.0.05). There were no significant correlations in T2DM subjects (n = 47). In control subjects (n = 63), serum cartonectin was significantly negatively correlated with CRP, and significantly positively correlated with insulin, HOMA-IR and leptin. However, when subjected to multiple regression analysis, none of these variables were predictive of serum cartonectin (P.0.05). Finally, serum cartonectin concentrations were significantly lower in T2DM subjects after a 2 hour 75 g OGTT (P,0.01). Conclusions: Cartonectin may serve as a novel biomarker for the prediction and early diagnosis of T2DM patients. Furthermore, cartonectin and/or pharmacological agents that increase circulating cartonectin levels can represent a new therapeutic field in the treatment of T2DM patients. Further research is needed to clarify these points. Citation: Ban B, Bai B, Zhang M, Hu J, Ramanjaneya M, et al. (2014) Low Serum Cartonectin/CTRP3 Concentrations in Newly Diagnosed Type 2 Diabetes Mellitus: In Vivo Regulation of Cartonectin by Glucose. PLoS ONE 9(11): e112931. doi:10.1371/journal.pone.0112931 Editor: Ranji Cui, Jilin University, China Received June 12, 2014; Accepted October 16, 2014; Published November 19, 2014 Copyright: ß 2014 Ban et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper. Funding: This work was supported by the National Nature Science Foundation of China (31271243 and 81070961), http://www.nsfc.gov.cn/publish/portal1/BBai, and the Natural Science Foundation of Shandong province (ZR2009CZ006 and ZR2011CM027), http://www.sdnsf.gov.cn/portal/BBan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * Email: B.K.Tan@warwick.ac.uk (BKT); Jing.Chen@warwick.ac.uk (JC) " B. Ban and B. Bai are joint first authors on this work; BKT and JC are joint senior authors on this work. Introduction Obesity has now achieved pandemic proportions and left unchecked, leads to atherosclerosis by causing a repertoire of metabolic and cardiovascular perturbations such as type 2 diabetes mellitus (T2DM), dyslipidemia and hypertension [1]. Adipose tissue produces several hormones and cytokines termed ‘adipo- kines’ that have widespread effects on carbohydrate and lipid metabolism, which appear to play an important role in the pathogenesis of insulin resistance, diabetes, and atherosclerosis [2,3]. Perturbations in adipokine concentrations have been reported in insulin resistant states such as gestational diabetes mellitus [4] and women with the Polycystic Ovary Syndrome (PCOS) [5]. Presently, there has been intense interest in the adipokines of the C1q complement/TNF-related protein (CTRP) superfamily. Foremost in this group is the adipokine adiponectin that circulates at high concentrations, and has insulin sensitizing, anti-inflamma- tory and anti-atherogenic properties [6]. Altered circulating adiponectin and adiponectin receptors levels have been described in patients with T2DM and insulin resistant states such as women PLOS ONE | www.plosone.org 1 November 2014 | Volume 9 | Issue 11 | e112931