Tentolouris N, Boutati E, Karambakalis N, Perrea D, Tselepis A D, Tsoukala C, Kyriaki D, Lourida E, Anastasopoulou I, Karafoullidou A, Raptis S A, Katsilambros N
First Department of Propaedeutic Medicine, Laiko Hospital, Athens University Medical School, Athens, Greece.
Nutr Metab Cardiovasc Dis. 2005 Feb;15(1):6-12. doi: 10.1016/j.numecd.2004.06.002.
Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes.
Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meal (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meal consumption and 6h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P<0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P=0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9+/-1.3 vs. -8.3+/-3.7 ng/ml h, P=0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P=0.001), although the overall response was not significantly different after nateglinide and placebo (P=0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo.
Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes.
餐后血糖和血脂是2型糖尿病患者动脉粥样硬化的已知危险因素。餐后状态下的凝血激活也会促进动脉粥样硬化的发展。那格列奈可有效降低餐后血糖。其对血糖的影响可能对餐后血脂和凝血也有益处。本研究的目的是探讨单剂量那格列奈对2型糖尿病患者餐后甘油三酯血症、凝血和纤维蛋白溶解的潜在影响。
在一项交叉随机研究中招募了10名仅通过饮食治疗的2型糖尿病受试者。早晨，在禁食12至14小时后，每位受试者在服用一片120毫克那格列奈或安慰剂后，进食标准混合餐（总能量783千卡）。在进餐前和进餐后6小时采集静脉血样，用于测量血浆葡萄糖、胰岛素、C肽、血脂、凝血和纤维蛋白溶解因子。正如预期的那样，与安慰剂相比，服用那格列奈后餐后血糖显著降低（P<0.001）。那格列奈组的血浆胰岛素水平显著高于安慰剂组（P=0.002）。与安慰剂相比，服用那格列奈后组织纤溶酶原激活物的餐后总体降低幅度较小（-2.9±1.3对-8.3±3.7纳克/毫升·小时，P=0.003）。此外，与那格列奈治疗后的基线值相比，餐后纤溶酶原激活物抑制剂-1显著降低（P=0.001），尽管那格列奈组和安慰剂组的总体反应无显著差异（P=0.31）。那格列奈组和安慰剂组之间的C肽、血脂浓度以及所研究的其余凝血参数无差异。
急性给予那格列奈可改善2型糖尿病患者的餐后血糖和纤维蛋白溶解活性。如果长期治疗研究证实这种联合效应，可能会降低2型糖尿病患者的心血管风险。
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