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 γ 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.