Serum CCN3 levels are increased in type 2 diabetes mellitus and associated with obesity, insulin resistance and inflammation

Background: CCN3 is a novel adipokine and has emerged as a potential metabolic regulator. However, information regarding the role of CCN3 in type 2 diabetes mellitus (T2DM) remains unclear. This study measured for the first time serum CCN3 levels in T2DM and explored the correlations between its serum levels and various metabolic parameters in humans. Methods: A total of 219 newly diagnosed T2DM (nT2DM) patients and 205 healthy control subjects, matched for age and sex ratio, were enrolled. Circulating CCN3 and TNF-alpha, IL-6 and MCP-1 were measured by ELISA. The anthropometric assessment and biochemical evaluation were done in all subjects. OGTT were performed in 34 healthy individuals to investigate the association of CCN3 with glucose. Results: Serum CCN3 levels were significantly higher in nT2DM patients compared to those of the healthy controls (6.71[4.88, 8.56] vs. 4.51[3.55, 5.99] ng/ml, P < 0.01). Serum CCN3 positively correlated with BMI, WC, FAT%, TG, FPG, 2 h-PG, HbA1c, FIns, HOMA-IR, hs-CRP and TNF-alpha, IL-6 and MCP-1, but negatively with HOMA-beta in all individuals (P < 0.05). Multiple linear regression analysis indicated that BMI, HOMA-IR, TNF-alpha and MCP-1 were independently associated with CCN3. Multivariate logistic regression analysis demonstrated that CCN3 was correlated with nT2DM. Finally, area under ROC curve of CCN3 (gender and age adjusted) for predicting the presence of nT2DM was 0.725(95% CI: 0.676-0.773). After an oral glucose challenge, there was no obvious change in the circulating levels of CCN3 as compared to 0 min (P > 0.05). Conclusions: Elevation of CCN3 in nT2DM supports the hypothesis that CCN3 may serve as a risk factor associated with the pathogenesis of T2DM.