Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects
Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects
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肥胖与非糖尿病受试者中乙酰水杨酸的血小板抑制作用受损有关
DOI：
10.1038/sj.ijo.0802312
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发表时间：
2003
影响因子：
4.9
通讯作者：
H. Yki
中科院分区：
文献类型：
--
作者：
M. Tamminen;R. Lassila;J. Westerbacka;S. Vehkavaara;H. Yki
目的：血小板聚集对乙酰水杨酸（ASA）的反应显示出相当大的个体差异，其原因在很大程度上是未知的。我们确定胰岛素作用的变化是否与ASA对血小板的影响有关。受试者：共10例非肥胖（年龄50±3y， BMI 25±1kg /m2）和11例肥胖（年龄52±2y， BMI 32±1kg /m2）受试者。测量方法：采用正糖胰岛素钳技术测定葡萄糖摄取的胰岛素敏感性。采用Born浊度聚集计，在摄入50 mg ASA前和1 h后，评估四剂量花生四烯酸（AA）和二磷酸腺苷（ADP）在富血小板血浆中的血小板聚集反应。结果：肥胖组全身胰岛素敏感性（m值为4.5±0.6）比非肥胖组（7.1±0.6 mg/kg min， P<0.01）低36%。在ASA前，所有剂量的AA均诱导细胞完全聚集。摄入ASA后，在AA浓度为0.75、1和1.5 mmol/l时，ASA对非肥胖组最大聚集的抑制作用大于肥胖组（方差分析P=0.016）。高剂量（2和3 μmol/l） adp诱导的聚集在肥胖组也较少受到抑制。体内胰岛素敏感性（1 mmol/l AA组r= - 0.68， P<0.001）和BMI （1 mmol/l AA组r=0.58， P<0.01）与ASA给药后残留聚集密切相关。结论：这些数据表明肥胖胰岛素抵抗者对ASA的血小板抑制作用反应迟钝。如果这种钝化效应是单剂量ASA持续使用造成的，它可能会增加胰岛素抵抗个体动脉粥样硬化血栓形成的风险。
OBJECTIVE: Platelet aggregation responses to acetylsalicylic acid (ASA) show considerable interindividual variation, the causes of which are largely unknown. We determined whether variation in insulin action is associated with that of ASA on platelets.SUBJECTS: In all, 10 nonobese (age 50±3 y, BMI 25±1 kg/m2) and 11 obese (age 52±2 y, BMI 32±1 kg/m2) subjects.MEASUREMENTS: Insulin sensitivity of glucose uptake was determined by the euglycemic insulin clamp technique. Platelet aggregation responses to four doses of arachidonic acid (AA) and adenosine diphosphate (ADP) were assessed in platelet-rich plasma before and 1 h after ingestion of 50 mg ASA using Born's turbidometric aggregometer.RESULTS: Whole-body insulin sensitivity (M-value 0–180 min) was 36% lower in the obese (4.5±0.6) than the nonobese (7.1±0.6 mg/kg min, P<0.01) group. Before ASA, all doses of AA induced complete aggregation. After ASA ingestion, ASA inhibited maximal aggregation more in the nonobese than the obese group at AA concentrations of 0.75, 1 and 1.5 mmol/l (P=0.016 for ANOVA). ADP-induced aggregation at high doses (2 and 3 μmol/l) was also less inhibited in the obese group. In vivo insulin sensitivity (r=−0.68, P<0.001 for 1 mmol/l AA) and BMI (r=0.58, P<0.01 for 1 mmol/l AA) were closely correlated with residual aggregation after ASA administration.CONCLUSION: These data demonstrate that obese insulin-resistant subjects have a blunted response to platelet-inhibitory effect of ASA. If this blunted effect is of a single dose of ASA preserved in continuous use, it could contribute to the increased risk of atherothrombosis in insulin-resistant individuals.
影响因子：
158.5
作者：
PEDERSEN, AK;FITZGERALD, GA
通讯作者：
FITZGERALD, GA
影响因子：
8.7
作者：
Cayatte, AJ;Du, Y;Cohen, RA
通讯作者：
Cohen, RA