title: Effect of simvastatin and fenofibrate on cytokine release and systemic inflammation in type 2 diabetes mellitus with mixed dyslipidemia.
abstract: The aim of our study was to compare the effect of simvastatin and fenofibrate treatment on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetes and to assess whether their coadministration is superior to treatment with only 1 of these drugs. One hundred ninety-six adult patients with recently diagnosed and previously untreated type 2 diabetes and mixed dyslipidemia, complying throughout the study with lifestyle intervention and treated with metformin, were randomized in a double-blind fashion to receive simvastatin (40 mg), fenofibrate (200 mg), simvastatin plus fenofibrate, or placebo for 90 days. Main outcome measurements were monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein. One hundred ninety patients completed the study. Simvastatin and fenofibrate decreased monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 and lymphocyte release of interleukin-2, interferon-γ, and tumor necrosis factor-α, which was accompanied by a decrease in plasma C-reactive protein levels. Anti-inflammatory effects of fenofibrate partly correlated with the improvement in insulin sensitivity. Lymphocyte-suppressing, but not monocyte-suppressing, effect was stronger if these 2 agents were administered together. In conclusion, simvastatin and fenofibrate exhibit a similar effect on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetic subjects with mixed dyslipidemia. This effect may be clinically relevant in the prevention of vascular complications in metformin- and diet-treated subjects with newly diagnosed diabetic dyslipidemia.
authors.affiliation: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland. r.krysiak@interia.pl
authors.forename: Robert
authors.initials: R
authors.lastname: Krysiak
authors.forename: Anna
authors.initials: A
authors.lastname: Gdula-Dymek
authors.forename: Bogusław
authors.initials: B
authors.lastname: Okopien
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008019:Life Style; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011446:Prospective Studies; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D001786:Blood Glucose; D002097:C-Reactive Protein; D016207:Cytokines; D011345:Fenofibrate; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008687:Metformin; D019821:Simvastatin; C517652:hemoglobin A1c protein, human