Haesler E, Golay A, Güzelhan C, Schutz Y, Hartmann D, Jéquier E, Felber J P
Institute of Physiology, Faculty of Medicine, University of Lausanne, Switzerland.
Int J Obes Relat Metab Disord. 1994 May;18(5):313-22.
The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.
这项单盲、安慰剂对照研究的目的是，在非糖尿病肥胖女性治疗两周前后，调查新型β-肾上腺素能化合物Ro 40-2148对静息能量消耗（REE）以及口服葡萄糖负荷后的影响。在服用一周安慰剂后，经过一夜禁食和一小时休息，在单次服用安慰剂溶液之前及之后6小时，通过间接测热法（头罩系统）测量REE以及葡萄糖和脂质氧化率。在此期间，在服用安慰剂90分钟后开始进行75克口服葡萄糖耐量试验（OGTT）。在接下来的两周内，采用随机设计，6名患者每天两次服用溶于100毫升水中的400毫克Ro 40-2148（即每天800毫克），而另外6名患者继续服用安慰剂。两周后重复相同的测试和测量，但治疗组服用药物而非安慰剂。14天的药物给药期并未增加在吸收后状态下测量的REE。同样，400毫克剂量的Ro 40-2148对REE也没有急性影响。相比之下，治疗组在两周后葡萄糖诱导的产热显著增加（平均值±标准误：3.7±1.3%，P = 0.047），而安慰剂组未观察到变化（-0.8±0.7%，无显著性）。由于呼吸商没有显著变化，治疗组观察到的能量消耗增加是由于脂质和葡萄糖氧化均受到刺激。该药物未引起心率、血压、腋窝温度或血浆葡萄糖、胰岛素和游离脂肪酸水平的变化。总之，本研究表明Ro 40-2148可激活肥胖非糖尿病患者的葡萄糖诱导产热。
