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阿西莫司对非肥胖2型糖尿病患者血脂、血糖控制及胰岛素作用影响的双盲研究。

A double blind study of the effect of acipimox on serum lipids, blood glucose control and insulin action in non-obese patients with type 2 diabetes mellitus.

作者信息

Fulcher G R, Catalano C, Walker M, Farrer M, Thow J, Whately-Smith C R, Alberti K G

机构信息

Department of Medicine, Medical School, University of Newcastle Upon Tyne, UK.

出版信息

Diabet Med. 1992 Dec;9(10):908-14. doi: 10.1111/j.1464-5491.1992.tb01730.x.

Abstract

Hyperlipidaemia, in particular raised concentrations of serum triglycerides, together with raised plasma non-esterified fatty acid concentrations, is common in patients with Type 2 (non-insulin-dependent) diabetes mellitus and may be associated with insulin insensitivity. Thirty non-obese Type 2 diabetic patients (15 controlled with diet alone and 15 with diet plus oral sulphonylurea therapy) were therefore recruited to take part in a double-blind, randomized, crossover comparison of acipimox (250 mg three times daily for 3 months) and placebo. Serum lipids, blood glucose control, insulin sensitivity, and glucose tolerance were measured before and after each treatment period. There was a significant decrease in serum triglycerides (2.05 +/- 1.08 vs 2.91 +/- 1.75: p < 0.005), cholesterol (5.66 +/- 1.02 vs 6.26 +/- 1.17: p = 0.0005), and apoprotein B (1.32 +/- 0.23 vs 1.44 +/- 0.25: p < 0.05) while HDL cholesterol and apoprotein A-1 concentrations were unchanged. There was no change in blood glucose control measured by fasting glucose, insulin, and HBA, concentrations, but there was a significant improvement in insulin action assessed by glucose-insulin infusion. Although plasma non-esterified fatty acid concentrations were lower during the oral glucose tolerance test after acipimox, there was no difference in either the peak or 2-h plasma glucose concentrations and the total area under the glucose curve did not change. Acipimox was well tolerated and no patients withdrew from the study for drug-related symptoms. Thus, acipimox effectively lowers serum cholesterol and triglycerides in patients with Type 2 diabetes without adversely altering blood glucose control, and appears to improve insulin sensitivity.

摘要

高脂血症,尤其是血清甘油三酯浓度升高,以及血浆非酯化脂肪酸浓度升高,在2型(非胰岛素依赖型)糖尿病患者中很常见,并且可能与胰岛素不敏感有关。因此,招募了30名非肥胖的2型糖尿病患者(15名仅通过饮食控制,15名采用饮食加口服磺脲类药物治疗),参与阿西莫司(每日三次,每次250毫克,共3个月)与安慰剂的双盲、随机、交叉对照试验。在每个治疗期前后测量血脂、血糖控制情况、胰岛素敏感性和葡萄糖耐量。血清甘油三酯(2.05±1.08对2.91±1.75:p<0.005)、胆固醇(5.66±1.02对6.26±1.17:p = 0.0005)和载脂蛋白B(1.32±0.23对1.44±0.25:p<0.05)显著降低,而高密度脂蛋白胆固醇和载脂蛋白A-1浓度未改变。通过空腹血糖、胰岛素和糖化血红蛋白浓度测量的血糖控制情况没有变化,但通过葡萄糖-胰岛素输注评估的胰岛素作用有显著改善。虽然在服用阿西莫司后的口服葡萄糖耐量试验期间血浆非酯化脂肪酸浓度较低,但峰值或2小时血浆葡萄糖浓度没有差异,葡萄糖曲线下的总面积也没有变化。阿西莫司耐受性良好,没有患者因药物相关症状退出研究。因此,阿西莫司能有效降低2型糖尿病患者的血清胆固醇和甘油三酯,且不会对血糖控制产生不利影响,似乎还能改善胰岛素敏感性。

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