Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose.

OBJECTIVE: Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged. Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin, as well as combined therapy, on fasting plasma glucose, insulin resistance index, adipokines (leptin, resistin, adiponectin) and levels of proinflammatory cytokines (TNF-α, IL-6) in patients with impaired fasting glucose (IFG) and mixed hyperlipidemia. MATERIALS AND METHODS: 67 patients were randomly assigned to four treatment arms: monotherapy with atorvastatin, monotherapy with fenofibrate, combined therapy (fenofibrate and torvastatin) or therapeutic lifestyle change. The study lasted for 90 days. All participants received counseling regarding proper diet and physical activity. RESULTS: Compared to the control subjects, prediabetic patients exhibited elevated plasma levels of leptin, resistin, TNF-α and IL-6, and a lower plasma level of adiponectin. All therapeutic interventions resulted in significant alterations in the lipid profile. Insulin resistance index (HOMA-IR) was reduced after treatment with fenofibrate. The effect of atorvastatin on insulin resistance was comparable to therapeutic lifestyle change alone. Therapy with hypolipidemic drugs caused increases in adiponectin levels and decreases in leptin and resistin. An additive effect of the combined treatment on plasma IL-6 level was also observed. CONCLUSIONS: Fenofibrate-based treatment was associated with improved insulin sensitivity. Atorvastatin did not cause a deterioration in insulin sensitivity. Hypolipidemic therapies resulted in significant changes in the proinflammatory cytokine network as well as in adipokine levels. At the end of the study the measured parameters nearly resembled those of the healthy subjects.