Insulin resistance as a determinant of platelet activation in obese women
Insulin resistance as a determinant of platelet activation in obese women
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DOI：
10.1016/j.jacc.2006.08.040
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发表时间：
2006-12-19
影响因子：
24
通讯作者：
Davi, Giovanni
中科院分区：
文献类型：
--
作者：
Basili, Stefania;Pacini, Giovanni;Davi, Giovanni
目的 我们检验了这样的假设：胰岛素抵抗本身会导致肥胖症患者血小板活化增加，而与潜在的炎症无关。 背景 肥胖、胰岛素抵抗和动脉粥样硬化是与低度炎症密切相关的现象。肥胖与其他健康女性的持续血小板活化有关。方法我们对 40 名肥胖和 20 名非肥胖健康女性进行了一项横断面研究，使用尿液中血栓素代谢物排泄作为血小板活化的非侵入性指标。测量了胰岛素敏感性、S 指数以及血浆脂联素、C 反应蛋白 (CRP) 和 CD40 配体 (CD40L) 水平。 结果 肥胖女性的 11-脱氢-血栓烷 B-2 (11-脱氢-TXB2) 排泄量显着较高 (p < 0.0001)（中位数 718 皮克/毫克 vs. 211 皮克/毫克） 肌酐）、CRP（1.13 vs. 0.48 mg/1）和 CD40L 水平（4.45 vs. 0.90 ng/ml）均高于对照组。与对照组相比，肥胖女性的 S（中位数 2.51 vs. 5.0 10(4) min(-1)/[mu U/ml]，p < 0.002）和脂联素（6.3 vs. 10 mu g/ml，p < 0.01）较低。在多元回归分析中，腰臀比（β = 0.27，p < 0.05）和 S（β = -0.72，p < 0.04）预测 11-脱氢-TXB2 排泄率，与脂联素、CRP、CD40L 和脂质模式无关。为了调查这些关联的因果关系，我们检查了 10 名 S-1 受损和内脏肥胖女性的 12 周减肥计划或 3 周吡格列酮治疗对尿 11-脱氢-TXB2 的影响。 5 名受试者成功减肥（每周减轻 0.6 公斤）与 S-1 增加 (+92%) 和 CD40L (-27%)、CRP (-37%) 和 11-脱氢-TXB2 (-53%) 减少相关 (p < 0.05)。一致地，吡格列酮对胰岛素敏感性的改善显着降低了尿 11-脱氢-TXB2 排泄量 (-43%，p < 0.05)，而体重没有变化。 结论 胰岛素抵抗是肥胖女性血小板活化的主要决定因素。
OBJECTIVES We tested the hypothesis that insulin resistance, per se, contributes to increased platelet activation in obesity, independently of underlying inflammation.BACKGROUND Obesity, insulin resistance, and atherosclerosis are closely linked phenomena associated with low-grade inflammation. Obesity is associated with persistent platelet activation in otherwise healthy women.METHODS We performed a cross-sectional study in 40 obese and 20 non-obese healthy women using urinary thromboxane metabolite excretion as a non-invasive index of platelet activation. An index of insulin sensitivity, S, and plasma adiponectin, C-reactive protein (CRP), and CD40 ligand (CD40L) levels were measured.RESULTS Obese women had significantly (p < 0.0001) higher 11-dehydro-thromboxane B-2 (11-dehydro-TXB2) excretion (median 718 vs. 211 pg/mg creatinine), CRP (1.13 vs. 0.48 mg/1), and CD40L levels (4.45 vs. 0.90 ng/ml) than controls. Obese women had lower S, (median 2.51 vs. 5.0 10(4) min(-1)/[mu U/ml], p < 0.002) and adiponectin (6.3 vs. 10 mu g/ml, p < 0.01) than control subjects. On multiple regression analysis, waist-to-hip ratio (beta = 0.27, p < 0.05) and S, (beta = -0.72, p < 0.04) predicted 11-dehydro-TXB2 excretion rate, independently of adiponectin, CRP, CD40L, and lipid patterns. In order to investigate the cause-effect relationship of these associations, we examined the effects of a 12-week weight loss program or a 3-week pioglitazone treatment on urinary 11-dehydro-TXB2 in 10 women with impaired S-1 and visceral obesity. Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with increased S-1 (+92%) and decreased CD40L (-27%), CRP (-37%), and 11-dehydro-TXB2 (-53%) (p < 0.05). Consistently, improvement of insulin sensitivity achieved with pioglitazone significantly decreased urinary 11-dehydro-TXB2 excretion (-43%, p < 0.05) without changes in body weight.CONCLUSIONS Insulin resistance is a major determinant of platelet activation in female obesity.