Differential effects of peroxisome proliferator-activated receptor ligands and sulfonylurea plus statin treatment on plasma concentrations of adipokines in type 2 diabetes with dyslipidemia.

OBJECTIVES Peroxisome proliferator-activated receptor gamma is the master regulator of adipocyte differentiation and controls many adipocyte genes in response to anti-diabetic thiazolidinediones (TZDs) and lipid-lowering fibrates. We hypothesized that the combination of TZD+fibrate may be better than the sulfonylurea + statin approach regarding modifying the adipokine profile in diabetic patients with dyslipidemia. METHODS We measured the lipid profiles and circulating levels of adiponectin, resistin, and inflammatory markers before and after treatment in 24 type 2 diabetic patients with dyslipidemia (aged 64+/-9 years; M/F=5/19). The study patients were randomly assigned to receive an 8-week treatment of either rosiglitazone 4 mg daily and fenofibrate 160 mg daily (PPAR group) or glibenclamide 5 mg daily and atorvastatin 10 mg daily (non-PPAR group). RESULTS Even though the administration of sulfonylurea+statin can achieve a greater reduction of total cholesterol and LDL-cholesterol levels and a comparable glucose control compared to PPAR treatment, their administration did not change the plasma adipokine levels significantly. In contrast, a significant greater increase of the plasma concentrations of adiponectin (P<0.0001), a trend to a greater decrease of the plasma resistin levels (P=0.061), a significantly greater increase of HDL-cholesterol (P=0.002), and a significantly greater reduction of triglyceride levels (P=0.018) were seen in the PPAR group. CONCLUSIONS Considering the clinical significance of the adipokine-endothelial interaction in the progression and long-term prognosis of atherosclerosis, the differential effects of PPAR ligands and sulfonylurea+statin on plasma adipokine concentrations demonstrated in this study are interesting foci of investigation in the future.