Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado, Aurora, Colorado 80045, USA.
Pharmacotherapy. 2010 Mar;30(3):236-47. doi: 10.1592/phco.30.3.236.
To determine the effects of the thiazolidinedione rosiglitazone on the adipocyte-derived cytokines adiponectin (an antiinflammatory and insulin-sensitizing cytokine; low levels have been associated with metabolic syndrome) and resistin (an inflammation mediator; high levels have been associated with metabolic syndrome) in nondiabetic patients with metabolic syndrome, and to characterize the effects of rosiglitazone on other components of the metabolic syndrome phenotype in this population.
Prospective, randomized, double-blind, placebo-controlled study.
Outpatient general clinical research center.
Thirty-two nondiabetic men and women with a clinical diagnosis of metabolic syndrome (as defined in the American Heart Association-National Heart, Lung, and Blood Institute scientific statement).
Patients were randomly assigned to receive either oral rosiglitazone 4 mg/day or matching placebo for 12 weeks.
The primary end point was change in serum adiponectin concentrations from baseline to week 12. Secondary end points were changes in serum resistin concentrations, insulin resistance, fasting glucose level, fasting insulin level, body weight, lipid levels, systolic and diastolic blood pressure, and waist circumference from baseline to week 12. Also, changes from baseline in adiponectin and resistin concentrations and insulin resistance were assessed over time at weeks 2, 4, 8, and 12. Rosiglitazone was associated with a significant increase in serum adiponectin concentration after 12 weeks compared with placebo (45.8% vs 2.6%, p=0.002). The increase in adiponectin concentration occurred quickly, with a significant difference observed after 2 weeks of therapy. Compared with placebo, rosiglitazone was not associated with significant 12-week changes in serum resistin concentrations, insulin resistance, fasting glucose level, fasting insulin level, body weight, lipid levels, systolic or diastolic blood pressure, or waist circumference.
Rosiglitazone had beneficial effects on adiponectin concentrations without significantly affecting other components of the metabolic syndrome phenotype. Additional studies that further elucidate the time course of thiazolidinedione pharmacodynamic effects, along with their effects on cardiovascular end points, are warranted in nondiabetic patients with metabolic syndrome.
在非糖尿病代谢综合征患者中，确定噻唑烷二酮类罗格列酮对脂肪细胞衍生细胞因子脂联素（一种抗炎和胰岛素增敏细胞因子；低水平与代谢综合征有关）和抵抗素（一种炎症介质；高水平与代谢综合征有关）的影响，并描述罗格列酮对该人群代谢综合征表型其他成分的影响。
前瞻性、随机、双盲、安慰剂对照研究。
门诊综合临床研究中心。
32 名临床诊断为代谢综合征（美国心脏协会-国家心肺血液研究所科学声明中定义）的非糖尿病男女患者。
患者随机接受罗格列酮 4 毫克/天或匹配安慰剂治疗 12 周。
主要终点是从基线到第 12 周血清脂联素浓度的变化。次要终点是从基线到第 12 周血清抵抗素浓度、胰岛素抵抗、空腹血糖水平、空腹胰岛素水平、体重、血脂水平、收缩压和舒张压以及腰围的变化。此外，还评估了从基线开始，在第 2、4、8 和 12 周时，脂联素和抵抗素浓度以及胰岛素抵抗的随时间变化。与安慰剂相比，罗格列酮治疗 12 周后血清脂联素浓度显著增加（45.8%对 2.6%，p=0.002）。脂联素浓度的增加很快，在治疗 2 周后就有显著差异。与安慰剂相比，罗格列酮在 12 周内对血清抵抗素浓度、胰岛素抵抗、空腹血糖水平、空腹胰岛素水平、体重、血脂水平、收缩压或舒张压或腰围无显著变化。
罗格列酮对脂联素浓度有有益影响，而对代谢综合征表型的其他成分无显著影响。在代谢综合征的非糖尿病患者中，需要进一步阐明噻唑烷二酮类药物药效学作用的时间过程及其对心血管终点的影响的研究。
