title: Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Internal Medicine and Clinical Pharmacology, Silesian Medical University, Medykow 18, 40-752 Katowice, Poland. lbuldak@gmail.com
authors.forename: Lukasz
authors.initials: L
authors.lastname: Buldak
authors.forename: Anna
authors.initials: A
authors.lastname: Dulawa-Buldak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Labuzek
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Okopien
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D044882:Glucose Metabolism Disorders / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006954:Hyperlipoproteinemia Type V / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011044:Poland; D011758:Pyrroles / Q000627:therapeutic use*; D052243:Resistin / Q000097:blood; D040242:Risk Reduction Behavior; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C499918:ADIPOQ protein, human; D054392:Adipokines; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; C508600:IL6 protein, human; D018836:Inflammation Mediators; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D008055:Lipids; D011758:Pyrroles; C499624:RETN protein, human; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D011345:Fenofibrate