Worm D, Henriksen J E, Vaag A, Thye-Rønn P, Melander A, Beck-Nielsen H
Diabetes Research Center, Odense University Hospital, Denmark.
J Clin Endocrinol Metab. 1994 Mar;78(3):717-21. doi: 10.1210/jcem.78.3.8126147.
Acute administration of the antilipolytic nicotinic acid analog acipimox to patients with noninsulin-dependent diabetes mellitus (NIDDM) is associated with increased peripheral and hepatic insulin sensitivity. However, long term acipimox treatment (250 mg, 3 times/24 h) of NIDDM patients does not improve blood glucose control, possibly due to rebound lipolysis. The current study assessed the influence of intensified acipimox administration (125 mg, 12 times/24 h) on diurnal plasma profiles of glucose, insulin, nonesterified FFA (NEFA), and triglycerides during a 3-day period. Eight NIDDM patients [mean age, 58.9 yr (range, 46-68); mean body mass index, 31.4 kg/m2 (range, 24.9-39.6)] were included in a randomized, double blind, placebo-controlled, cross-over study. Blood samples were collected every second hour during the study. The acipimox and placebo treatments were separated by a 2-week washout period. Acipimox treatment was associated with reduced diurnal mean plasma concentrations of NEFA [0.26 +/- 0.03 (+/- SEM) vs. 0.63 +/- 0.06 mmol/L; P < 0.001], triglycerides (1.74 +/- 0.21 vs. 2.10 +/- 0.18 mmol/L; P < 0.03), glucose (12.7 +/- 1.0 vs. 15.8 +/- 1.2 mmol/L; P < 0.002), and insulin (157 +/- 21 vs. 207 +/- 27 pmol/L; P < 0.05). However, despite the overall reduction in mean NEFA, during acipimox treatment NEFA increased from days 1-3 (0.18 +/- 0.03 vs. 0.34 +/- 0.04 mmol/L; P < 0.001), whereas plasma glucose (13.4 +/- 1.2 vs. 12.3 +/- 0.9 mmol/L; P < 0.03) and plasma insulin (168 +/- 23 vs. 148 +/- 17 pmol/L; P < 0.04) decreased steadily from days 1-3 during active treatment. In conclusion, inhibition of lipolysis using the intensified acipimox treatment regiment was associated with a pronounced blood glucose- and plasma insulin-lowering effect. However, minor rebound effects of lipolysis occurred in some patients despite the presence of allegedly effective acipimox levels. This suggests that caution should be employed concerning long term use of acipimox as a hypoglycemic agent in NIDDM patients.
对非胰岛素依赖型糖尿病（NIDDM）患者急性给予抗脂解烟酸类似物阿西莫司，可使外周和肝脏胰岛素敏感性增加。然而，对NIDDM患者进行长期阿西莫司治疗（250毫克，每24小时3次）并不能改善血糖控制，这可能是由于脂解作用反弹所致。本研究评估了强化阿西莫司给药（125毫克，每24小时12次）在3天期间对葡萄糖、胰岛素、非酯化游离脂肪酸（NEFA）和甘油三酯的日间血浆水平的影响。8名NIDDM患者[平均年龄58.9岁（范围46 - 68岁）；平均体重指数31.4千克/平方米（范围24.9 - 39.6）]被纳入一项随机、双盲、安慰剂对照、交叉研究。在研究期间每两小时采集一次血样。阿西莫司治疗和安慰剂治疗之间间隔2周的洗脱期。阿西莫司治疗使NEFA的日间平均血浆浓度降低[0.26±0.03（±标准误）对0.63±0.06毫摩尔/升；P<0.001]，甘油三酯（1.74±0.21对2.10±0.18毫摩尔/升；P<0.03），葡萄糖（12.7±1.0对15.8±1.2毫摩尔/升；P<0.002），以及胰岛素（157±21对207±27皮摩尔/升；P<0.05）。然而，尽管平均NEFA总体上有所降低，但在阿西莫司治疗期间，NEFA在第1 - 3天有所增加（0.18±0.03对0.34±0.04毫摩尔/升；P<0.001），而血浆葡萄糖（13.4±1.2对12.3±0.9毫摩尔/升；P<0.03）和血浆胰岛素（168±23对148±17皮摩尔/升；P<0.04）在积极治疗的第1 - 3天稳步下降。总之，使用强化阿西莫司治疗方案抑制脂解作用与显著降低血糖和血浆胰岛素的作用相关。然而，尽管存在据称有效的阿西莫司水平，但部分患者仍出现了轻微的脂解反弹效应。这表明在NIDDM患者中长期使用阿西莫司作为降糖药物时应谨慎。
