Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus.

Visfatin is a newly identified adipocytokine that mimics insulin action. However, the pathophysiological role of visfatin in diabetic patients is not fully understood. The main purpose of this study was to investigate the association of plasma visfatin with endothelial function in patients with type 2 diabetes mellitus. In addition, the relationships of visfatin with oxidative stress, low-grade inflammation, atherosclerosis, adiponectin, plasma renin activity, and aldosterone were also explored, and the effect of pioglitazone on visfatin was examined. Visfatin levels were measured in 80 patients with type 2 diabetes mellitus and in 28 age-matched healthy subjects. Endothelial function was evaluated by using flow-mediated vasodilatation (FMD), oxidative stress was assessed by the level of urinary 8-iso-prostaglandin F2alpha, and atherosclerosis and inflammation were measured by using the intimal-medial complex thickness and the levels of high-sensitivity C-reactive protein and fibrinogen. Pioglitazone was administered for 12 weeks at a dose of 30 mg/d in a further 20 patients with type 2 diabetes mellitus. There was a significant negative correlation between the log10-transformed (log) plasma visfatin concentration and FMD or creatinine clearance (R=-0.2672, P=.0167; R=-0.2750, P=.0136). Log visfatin was also positively correlated with log urinary albumin excretion (R=0.2305, P=.0397). In addition, it was also found that visfatin had a significant negative correlation with plasma aldosterone (R=-0.2432, P=.0297). In stepwise regression analysis, creatinine clearance, log aldosterone, FMD, and sex showed a significant association with log visfatin (P=.0040, P=.0069, P=.0444, and P=.0487, respectively), and log 8-iso-prostaglandin F2alpha showed a tendency for an association (P=.0515). Pioglitazone therapy did not affect the visfatin concentration in the 20 pioglitazone-treated patients with diabetes, although a significant elevation of visfatin was obtained in a subgroup of 11 female patients (P=.0381). In conclusion, the current study showed that visfatin is negatively associated with vascular endothelial function evaluated by FMD and creatinine clearance, and positively associated with log urinary albumin excretion. Visfatin was also negatively correlated with circulating aldosterone. Pioglitazone therapy for 12 weeks did not affect the plasma visfatin concentration significantly in all diabetic patients, but a significant elevation in visfatin was obtained in women only.