Rizzo M R, Barbieri M, Grella R, Passariello N, Paolisso G
Department of Geriatrics and Metabolic Diseases, II University of Naples, Naples, Italy.
Diabetes Metab. 2005 Jun;31(3 Pt 1):255-60. doi: 10.1016/s1262-3636(07)70192-1.
Aim our study is to compare the effects of repaglinide vs glimepiride administration on cardiovascular risk factors after meal test. Thus, after 2 weeks washout period, a 3-month randomised, cross-over parallel group trial of repaglinide (1 mg x 2/day) vs glimepiride (2 mg/day) in 14 patients with type 2 diabetes "naive" on diet treatment was made. Both treatments significantly declined plasma glucose, total-cholesterol, LDL-cholesterol, triglycerides, PAI-1, PAP levels and increased HDL-cholesterol. Lowering in plasma PAI-1 and PAP levels was significantly greater in repaglinide group. Furthermore, repaglinide administration resulted in a significant decrease in fasting plasma free fatty acids, fibrinogen, thrombin-antithrombin complex and reaction product of malondialdehyde with thiobarbituric acid (TBARS) levels, in absence of significant difference in fasting plasma insulin levels. Decrease in plasma TBARS levels correlated with the decrease in Plasminogen Activator Inhibitor-1 (r = 0.72; P < 0.003) and free fatty acids concentrations (r = 0.62; P < 0.01). Analysis of the insulin and glucose concentrations throughout the meal test revealed that AUC for glucose (758 +/- 19 vs 780 +/- 28 mg/Lxmin; P = 0.02) was significantly lower after repaglinide than glimepiride administration despite similar AUC for insulin (2327 +/- 269 vs 2148 +/- 292 mU/Lxmin; P = 0.105). At time 120' of meal test, repaglinide vs glimepiride administration was associated with a significant decline in plasma triglycerides, free fatty acids, fibrinogen, Plasminogen Activator Inhibitor-1, plasmin-alpha(2)-antiplasmin complex, thrombin-antithrombin complex, TBARS levels and increase in plasma HDL-cholesterol levels. In repaglinide group a negative correlation between insulin secretion during 1st phase of meal-test and plasma TBARS levels (r = -0.55; P < 0.03) at time 120' was found. Such correlation was lost after adjusting for changes in postprandial hyperglycaemia (r = -0.48; P < 0.09). In conclusion, our results support the hypothesis that repaglinide is more efficient than glimepiride on controlling for postprandial glucose excursion and may have beneficial effect on reducing cardiovascular risk factors.
我们的研究旨在比较瑞格列奈与格列美脲给药对餐后试验中心血管危险因素的影响。因此，在2周的洗脱期后，对14例接受饮食治疗的初治2型糖尿病患者进行了一项为期3个月的随机、交叉平行组试验，比较瑞格列奈（1mg×2/天）与格列美脲（2mg/天）的疗效。两种治疗均显著降低了血浆葡萄糖、总胆固醇、低密度脂蛋白胆固醇、甘油三酯、PAI-1、PAP水平，并提高了高密度脂蛋白胆固醇水平。瑞格列奈组血浆PAI-1和PAP水平的降低幅度明显更大。此外，瑞格列奈给药导致空腹血浆游离脂肪酸、纤维蛋白原、凝血酶-抗凝血酶复合物以及丙二醛与硫代巴比妥酸反应产物（TBARS）水平显著降低，而空腹血浆胰岛素水平无显著差异。血浆TBARS水平的降低与纤溶酶原激活物抑制剂-1（r = 0.72；P < 0.003）和游离脂肪酸浓度（r = 0.62；P < 0.01）的降低相关。对进餐试验全过程中胰岛素和葡萄糖浓度的分析显示，尽管胰岛素的曲线下面积（AUC）相似（2327±269 vs 2148±292 mU/L·min；P = 0.105），但瑞格列奈给药后葡萄糖的AUC（758±19 vs 780±28 mg/L·min；P = 0.02）显著低于格列美脲给药后。在进餐试验120分钟时，与格列美脲给药相比，瑞格列奈给药使血浆甘油三酯、游离脂肪酸、纤维蛋白原、纤溶酶原激活物抑制剂-1、纤溶酶-α2-抗纤溶酶复合物、凝血酶-抗凝血酶复合物、TBARS水平显著降低，血浆高密度脂蛋白胆固醇水平升高。在瑞格列奈组，发现进餐试验第一阶段胰岛素分泌与120分钟时血浆TBARS水平呈负相关（r = -0.55；P < 0.03）。在校正餐后高血糖变化后，这种相关性消失（r = -0.48；P < 0.09）。总之，我们的结果支持以下假设：瑞格列奈在控制餐后血糖波动方面比格列美脲更有效，并且可能对降低心血管危险因素具有有益作用。
