Serum levels of WISP1/CCN4 in subjects with type 2 diabetes: the relationships with body fat distribution and adipose tissue dysfunction

The aim: to assess the relationships between the circulating Wnt1-inducible signaling pathway protein 1 (WISP1) and the levels of other adipokines, inflammatory markers, fat mass and fat distribution, and parameters of glycemic control in type 2 diabetic subjects. Materials and Methods: We observed 156 patients, 45 M/111 F, including 102 subjects with obesity. The levels of WISP1, hsCRP, alpha1-acid glycoprotein (AGP), and macrophage inflammatory protein 1alpha (MIP-1alpha) were measured in the fasting serum by ELISA. Serum concentrations of leptin, resistin, visfatin, adipsin, adiponectin, IL-6, IL-8, IL-18 and TNF-alpha were determined by Multiplex analysis. Twenty four non-obese non-diabetic subjects, matched by age and sex, were acted as control. The fat mass and distribution was assessed by DEXA. The mean diameter of adipocytes was estimated in the samples of subcutaneous AT in 25 patients. Glucose variability (GV) parameters were derived from continuous glucose monitoring. Results: Patients with diabetes, as compared to control, had significantly higher levels of WISP1 (p=0.02), leptin (p=0.005), resistin (p<;0.0001), adipsin (p<;0.0001), visfatin (p=0.0003), hsCRP (p<;0.0001), AGP (p<;0.0001), MIP-1alpha (p=0.006) and IL-6 (p=0.01). Serum WISP1 levels demonstrated positive correlations with percentage of android fat mass (r=0.46, p<;0.001), resistin, visfatin and MIP-1alpha levels (r=0.36, r=0.28 and r=0.47 respectively, all p<;0.01), but it did not correlated with HbA1c and GV parameters. In a multiple regression analysis android fat mass was the only reliable predictor of serum WISP1 levels. Conclusions: In subjects with type 2 diabetes serum levels of circulating WISP1 are associated with adiposity and adipose tissue dysfunction.