Centre of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy.
J Thromb Haemost. 2010 Apr;8(4):828-37. doi: 10.1111/j.1538-7836.2010.03742.x. Epub 2010 Jan 17.
Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus.
To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients.
Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE).
Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001).
Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.
慢性高血糖是糖尿病患者体内血小板活化的主要原因。
评估阿卡波糖，一种α-葡萄糖苷酶抑制剂，对新诊断的 2 型糖尿病患者血小板活化及其决定因素的影响。
48 名受试者（26 名男性，年龄 61±8 岁）患有早期 2 型糖尿病（基线糖化血红蛋白 A1c≤7%，且无既往低血糖治疗），随机分为阿卡波糖 100mg 每日 3 次或安慰剂组，每 4 周评估 20 周。主要观察指标为尿 11-脱氢血栓素 B2（体内血小板活化的标志物）和 8-异前列腺素 F2α（体内脂质过氧化的标志物）排泄率、餐后 2 小时血糖（PPG）和平均血糖波动幅度（MAGE）评估血糖波动。
基线测量显示生化证据表明脂质过氧化和血小板活化增强。与安慰剂组相比，阿卡波糖治疗组早在 8 周后，并且在随后的每个时间点（12、16 和 20 周时组间 P<0.0001），尿 11-脱氢血栓素 B2 和 8-异前列腺素 F2α排泄率均有统计学显著降低，随后 PPG 和 MAGE 降低。阿卡波糖组的多元回归分析显示，PPG 是尿 11-脱氢血栓素 B2 排泄率的唯一显著预测因子（β=0.39，P=0.002），MAGE 是尿 8-异前列腺素 F2α 排泄率的唯一预测因子（β=0.42，P=0.001）。
早期 2 型糖尿病患者餐后高血糖与脂质过氧化和血小板活化增强有关。阿卡波糖可适度降低 PPG，从而导致这些现象的时间依赖性下调，表明在这种情况下，早期代谢异常与血小板活化之间存在因果关系。
