Research Article: Serum levels of CTRP3 in diabetic nephropathy and its relationship with insulin resistance and kidney function

Date Published: April 22, 2019

Publisher: Public Library of Science

Author(s): Nariman Moradi, Reza Fadaei, Mohammad Ebrahim Khamseh, Ali Nobakht, Mohammad Jafar Rezaei, Fereshteh Aliakbary, Akram Vatannejad, Jalil Hosseini, Jonathan M Peterson.


C1q TNF related protein 3 (CTRP3) is an adipokine secreted from adipose tissue. Previous studies have suggested that CTRP3 improves insulin sensitivity and reduces inflammation. Human studies have evaluated circulating levels of this adipokine in patients with diabetes mellitus (DM), diabetic retinopathy, metabolic syndrome, and coronary artery diseases. However, circulating levels of this adipokine in patients with diabetic nephropathy have not been evaluated. The present study aimed to assess serum levels of CTRP3 in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (T2DM-NP) and its relationship with metabolic and inflammatory markers.

This cross-sectional study was performed on 55 controls, 54 patients with T2DM, and 55 patients with T2DM-NP. Serum levels of CTRP3, adiponectin, TNF-α, and IL-6 were measured by ELISA technique.

Serum levels of CTRP3 were significantly lower in patients with T2DM (257.61 ± 69.79 ng/mL, p < 0.001) and T2DM-NP (222.03 ± 51.99 ng/mL, p < 0.001) compared to controls (328.17 ± 80.73 ng/mL), and those with T2DM-NP compared to T2DM group. CTRP3 was independently associated with HOMA-IR (r = -0.327, p < 0.05) and adiponectin (r = 0.436, p < 0.01) in T2DM group. In T2DM-NP patients, CTRP3 independently was associated with eGFR (r = 0.428, p < 0.01) and HOMA-IR (r = -0.436, p < 0.01). Furthermore, CTRP3 revealed a ability to differentiate T2DM-NP patients from controls (area under curve (95% confidence interval): 0.881 (0.820–0.943) and p < 0.001). Decreased serum levels of CTRP3 in patients with T2DM and diabetic nephropathy and its association with pathologic mechanism in these patients suggested a possible role for CTRP3 in pathogenesis of diabetic nephropathy; nevertheless, further studies are required in this regard.

Partial Text

Adipose tissue is an active endocrine organ which secrets bioactive molecules called adipokine [1]. These molecules constitute a link between adipose tissue function and physiological and pathophysiological processes in the body such as glucose and lipid metabolism, endothelial functions, and inflammation [1]. Adipokines have shown to be potential biomarkers and therapeutic targets for diabetes mellitus (DM) and its complications [2].

CTRP3 is the most studied member of CTRP family and several studies evaluated its circulating levels in the context of cardio-metabolic diseases [10, 16, 17, 19]. Nevertheless, circulating levels of this adipokine have not been studied in patients with kidney diseases. Most previous studies reported lower levels of CTRP3 in patients with T2DM [8, 24, 25]; however, a study by Choi et. al. showed higher levels of CTRP3 in patients with T2DM [26]. They developed an ELISA for measuring CTRP3 that is different from the ELISA kit was used in the present study. The difference between methods used for measuring CTRP3 could be a possible cause for this contradiction. Furthermore, several studies also indicated in vivo association between CTRP3 and parameters of glucose metabolism [27]. Ban et. al. reported lower levels of CTRP3 in newly diagnosed T2DM patients [24], and Deng et al. showed lower concentrations of CTRP3 in obesity and hypertension [27]. In line with previous studies, in the present study, CTRP3 serum levels were significantly lower in patients with T2DM. Furthermore, CTRP3 was negatively correlated with insulin and HOMA-IR across all studied groups. Various studies suggested a negative correlation between HOMA-IR and CTRP3 in patients with cardio-metabolic diseases [3, 8, 25]. Lower levels of CTRP3 in T2DM and negative correlation between CTRP3 and HOMA-IR could be caused by the effect of insulin resistance on the expression of this adipokine in adipose tissue. Confirming this statement, previous studies revealed that insulin resistance reduced the expression of CTRP3. On the other hand, CTRP3 exerts multiple effects on insulin and glucose metabolism [11]. CTRP3 lowers glucose levels in mice and suppresses gluconeogenesis genes [12]. In addition, it has been revealed that CTRP3 improves insulin sensitivity by reducing inflammation in 3T3-L1 adipocytes [13]. Furthermore, CTRP3 enhances protein kinase B (PKB) and AMPK phosphorylation and promote expression of phosphoinositide 3-kinase (PI3K) and Glucose transporter type 4 (GLUT-4), improving insulin sensitivity in adipocytes [11]. Therefore, the reduced CTRP3 seems to be due to insulin resistance and might be a factor which exacerbates insulin resistance in patients with T2DM.