Arakawa Masayuki, Ebato Chie, Mita Tomoya, Fujitani Yoshio, Shimizu Tomoaki, Watada Hirotaka, Kawamori Ryuzo, Hirose Takahisa
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
Metabolism. 2008 Sep;57(9):1299-306. doi: 10.1016/j.metabol.2008.04.027.
Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis. Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of alpha-glucosidase inhibitors. Alpha-glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 (GLP-1) secretion. We compared the postprandial effects of a single administration of miglitol and acarbose on glucose and lipid metabolism, on insulin requirement, on GLP-1 secretion, and on inflammatory and endothelial markers in viscerally obese subjects. Twenty-four viscerally obese subjects with relative insulin resistance participated in this study. Subjects were given a single dose of miglitol (50 mg), acarbose (100 mg), or placebo blindly and randomly before a meal in a crossover design. The meal loads after drug administration were tested 3 times within 2 weeks. We measured glucose, insulin, lipids, lipoprotein lipase, interleukin 6, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and active GLP-1 at before and various minutes after the meal. Single administration of both alpha-glucosidase inhibitors had several beneficial effects in improving postprandial hyperglycemia and reducing postprandial insulin requirement approximately 25% of placebo without adversely affecting lipid profiles. Although lipoprotein lipase levels within 2 hours after the meal did not show differences among miglitol, acarbose, and placebo administrations, miglitol significantly suppressed the increases in triglycerides, remnant-like particle triglycerides, and remnant-like particle cholesterol compared to acarbose and placebo in the early phase. Miglitol also significantly enhanced active GLP-1 secretion to a greater extent than acarbose (P < .01) and placebo (P < .001), and significantly suppressed the postprandial increase in interleukin 6 compared to placebo (P < .01). The results point to the potential suitability of miglitol as an anti-atherosclerotic effect in viscerally obese subjects, in preference to acarbose. Further studies are needed to elucidate the long-term effects on enhanced GLP-1 secretion and anti-atherosclerosis.
内脏肥胖和胰岛素抵抗被视为动脉粥样硬化的危险因素。流行病学研究表明,给予α-葡萄糖苷酶抑制剂具有长期抗动脉粥样硬化作用。据报道,α-葡萄糖苷酶抑制剂还可增强胰高血糖素样肽1(GLP-1)的分泌。我们比较了单次服用米格列醇和阿卡波糖对内脏肥胖受试者的葡萄糖和脂质代谢、胰岛素需求、GLP-1分泌以及炎症和内皮标志物的餐后影响。24名具有相对胰岛素抵抗的内脏肥胖受试者参与了本研究。采用交叉设计,受试者在餐前被盲目随机给予单剂量米格列醇(50mg)、阿卡波糖(100mg)或安慰剂。给药后2周内对餐食负荷进行3次测试。我们在餐前和餐后不同时间点测量了葡萄糖、胰岛素、脂质、脂蛋白脂肪酶、白细胞介素6、细胞间黏附分子1、血管细胞黏附分子1和活性GLP-1。两种α-葡萄糖苷酶抑制剂单次给药在改善餐后高血糖和将餐后胰岛素需求降低约为安慰剂的25%方面具有多种有益作用,且对脂质谱无不利影响。尽管餐后2小时内脂蛋白脂肪酶水平在米格列醇、阿卡波糖和安慰剂给药之间未显示差异,但在早期阶段,与阿卡波糖和安慰剂相比,米格列醇显著抑制了甘油三酯、残粒样颗粒甘油三酯和残粒样颗粒胆固醇的升高。米格列醇还比阿卡波糖(P <.01)和安慰剂(P <.001)更显著地增强了活性GLP-1的分泌,并且与安慰剂相比(P <.01)显著抑制了餐后白细胞介素6的升高。结果表明,与阿卡波糖相比,米格列醇对内脏肥胖受试者具有抗动脉粥样硬化作用的潜在适用性。需要进一步研究以阐明对增强GLP-1分泌和抗动脉粥样硬化的长期影响。