title: Downregulation of the proinflammatory state of circulating mononuclear cells by short-term treatment with pioglitazone in patients with type 2 diabetes mellitus and coronary artery disease.
abstract: Background. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers). Methods and Results. Sixty-three patients with well-controlled type 2 diabetes (52 males, 11 females, age (Mean ± SD): 66 ± 7 yrs, disease duration: 6.6 ± 9.6 yrs, HbA1c: 6.7 ± 0.6%) were randomized to additional 45 mg of pioglitazone or placebo to their existing metformin and sulfonylurea therpay for four weeks in a double-blind study design. Protein risk marker levels (hsCRP, MMP-9, MCP-1, etc.) and the expression of NFκB subunits and NFκB-modulated cytokines from isolated peripheral monocyte/macrophages were determined at baseline and endpoint. There were no changes in HbA1c, but significant biomarker improvements were seen with pioglitazone only. The mRNA marker expression was downregulated by pioglitazone and further up-regulated with placebo (e.g., P105 pioglitazone: -19%/placebo: +6%, RelA: -20%/+2%, MMP-9: -36%/+9%, TNFα: -10%/+14%, P < 0.05 between groups in all cases). Conclusions. Pioglitazone very rapidly down-regulated the activated state of peripheral monocytes/macrophages as assessed by mRNA expression of NFκB and NFκB-modulated cytokines and decreased plasma levels of cardiovascular risk marker proteins independent of glycemic control.
authors.affiliation: IKFE Institute for Clinical Research and Development, Research Laboratory, 55116 Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.forename: Alexander
authors.initials: A
authors.lastname: Weise
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pfützner-Riehn
authors.forename: Georg
authors.initials: G
authors.lastname: Lübben
authors.forename: Michael
authors.initials: M
authors.lastname: Morcos
authors.forename: Efstrathios
authors.initials: E
authors.lastname: Karagiannis
authors.forename: Matthias
authors.initials: M
authors.lastname: Weber
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst