Circulating Levels of C1q/TNF-Related Protein-12 (CTRP-12) in Patients with Type 2 Diabetes: A Case-control Study

Document Type : Original Article


1 Assistant Professor, Department of Medical Laboratory Sciences, School of Allied Health Medicine, AJA University of Medical sciences, Tehran, Iran

2 Assistant Professor, Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran


Background: The C1q complement/TNF-related protein (CTRP) superfamily is a newly diagnosed adipokine with anti-inflammatory, insulin sensitivity, and glucose lowering effects. This study aimed to assess the plasma circulating levels of CTRP12 in type 2 diabetic (T2D) patients and healthy subjects.
Methods: In this case-control study, plasma concentration of CTRP12 was measured by ELISA in 60 subjects (30 T2D and 30 healthy participants). The systolic blood pressure (SBP), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured.
Results:In contrast to the SBP, WC, WHR, BMI, FBS, HbA1c, insulin, and HOMA-IR, the levels of CTRP12 were significantly lower in T2D patients. There was significant negative correlation between CTRP12, FBS, and HbA1c. The regression analysis showed that when subjected to stepwise multiple regression analysis, HbA1c (β = -2.21; P < 0.004) was predictive of plasma levels of CTRP12.
Conclusion: Finally, HbA1c was predictive of CTRP12 levels. It seems that CTRP12 could be considered as a novel biomarker for the prediction of T2D.


Organization WH. Classification of diabetes mellitus. 2019.
Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011; 11(2):85-97.
Khodabandehloo H, Gorgani-Firuzjaee S, Panahi G, Meshkani R. Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction.
Transl Res 2016; 167(1):228-56.
Lindberg S, Jensen JS, Pedersen SH, Galatius S, Frystyk J, Flyvbjerg A, et al. Low adiponectin levels and increased risk of type 2 diabetes in patients with myocardial infarction. Diabetes Care 2014; 37(11):3003-8.
Wang Y, Meng RW, Kunutsor SK, Chowdhury R, Yuan JM, Koh WP, et al. Plasma adiponectin levels and type 2 diabetes risk: a nested case-control study in a Chinese population and an updated meta-analysis. Sci Rep 2018; 8(1):406.
Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002; 277(29):25863-6.
Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002; 8(7):731-7.
Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, et al. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor γ agonists. J Biol Chem 2006; 281(5):2654-60.
Davis KE, Scherer PE. Adiponectin: no longer the lone soul in the fight against insulin resistance? Biochem J 2008; 416(2):e7-9.
Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Revett T, Gimeno R, Lodish HF. Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem J 2008; 416(2):161-77.
Flehmig G, Scholz M, Kloting N, Fasshauer M, Tonjes A, Stumvoll M, et al. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PLoS One 2014; 9(6):e99785.
Schaffler A, Buechler C. CTRP family: linking immunity to metabolism. Trends Endocrinol Metab 2012; 23(4):194-204.
Wong GW, Wang J, Hug C, Tsao TS, Lodish HF. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci U S A 2004; 101(28):10302-7.
Bell-Anderson KS, Funnell AP, Williams H, Jusoh HM, Scully T, Lim WF, et al. Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2). Diabetes 2013; 62(8):2728-37.
Enomoto T, Ohashi K, Shibata R, Higuchi A, Maruyama S, Izumiya Y, et al. Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism. J Biol Chem 2011; 286(40):34552-8.
Tan BK, Chen J, Adya R, Ramanjaneya M, Patel V, Randeva HS. Metformin increases the novel adipokine adipolin/CTRP12: role of the AMPK pathway. J Endocrinol 2013; 219(2):101-8.
Tan BK, Chen J, Hu J, Amar O, Mattu HS, Ramanjaneya M, et al. Circulatory changes of the novel adipokine adipolin/CTRP12 in response to metformin treatment and an oral glucose challenge in humans. Clin Endocrinol (Oxf) 2014; 81(6):841-6.
Tan BK, Lewandowski KC, O'Hare JP, Randeva HS. Insulin regulates the novel adipokine adipolin/CTRP12: in vivo and ex vivo effects. J Endocrinol 2014; 221(1):111-9.
Wei Z, Peterson JM, Lei X, Cebotaru L, Wolfgang MJ, Baldeviano GC, et al. C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes. J Biol Chem 2012; 287(13):10301-15.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33(Suppl 1):S62–9.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7):412-9.
Bai B, Ban B, Liu Z, Zhang MM, Tan BK, Chen J. Circulating C1q complement/TNF-related protein (CTRP) 1, CTRP9, CTRP12 and CTRP13 concentrations in Type 2 diabetes mellitus: In vivo regulation by glucose. PloS One 2017; 12(2):e0172271.
Enomoto T, Shibata R, Ohashi K, Kambara T, Kataoka Y, Uemura Y, et al. Regulation of adipolin/CTRP12 cleavage by obesity. Biochem Biophys Res Commun 2012; 428(1):155-9.
Wei Z, Peterson JM, Lei X, Cebotaru L, Wolfgang MJ, Baldeviano GC, et al. C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes. J Biol Chem 2012; 287(13):10301-15.
Mehrdadi P, Mohammadi RK, Alipoor E, Eshraghian MR, Esteghamati A, Hosseinzadeh-Attar M. The effect of coenzyme q10 supplementation on circulating levels of novel adipokine adipolin/CTRP12 in overweight and obese patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2017; 125(03):156-62.