Gudbjörnsdóttir S, Fowelin J, Elam M, Attvall S, Bengtsson B A, Mårin P, Lönnroth P
Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Eur J Clin Invest. 1997 Jan;27(1):29-35. doi: 10.1046/j.1365-2362.1997.670617.x.
To evaluate the effect of metoprolol on insulin sensitivity and diurnal plasma hormone levels, seven mildly hypertensive subjects were investigated (four men and three women, age 52 +/- 8, body mass index 25.4 +.- 1.9, mean +/- SD). The study had a placebo-controlled, double-blind, crossover design with 6 weeks' metoprolol treatment (100 mg b.i.d) vs. placebo. At the end of each treatment period 24-h blood samples were collected continuously for diurnal analysis of hormone levels and a hyperinsulinaemic euglycaemic clamp combined with [3-3H]-D-glucose infusion was performed. Insulin sensitivity was evaluated by means of three different methods: diurnal plasma insulin and glucose levels; glucose consumption; and insulin sensitivity index during euglycaemic clamp conditions. Fasting blood glucose and insulin concentrations as well as mean plasma diurnal levels of insulin, growth hormone, testosterone and cortisol were similar after placebo and metoprolol treatment, whereas noradrenaline and adrenaline levels were significantly increased after metoprolol. During the clamp, plasma insulin was significantly higher after metoprolol treatment than after placebo treatment (56 +/- 3 vs. 64 +/- 2 mU L(-1), P < 0.05). Consequently, the insulin sensitivity index [glucose infusion rate (GIR)/ plasma insulin] was lower after metoprolol treatment (16.1 +/- 2.6 vs. 10.2 +/- 1.2, P < 0.05), although GIR was not significantly changed. We suggest that the insulin sensitivity index may not accurately reflect the insulin effect as the plasma level of insulin was significantly increased during insulin infusion but not at 24 h, possibly because of alteration of distribution and/or degradation rate of exogenous insulin. Thus, the likelihood of metoprolol inducing insulin resistance in hypertensive subjects may be less than previously proposed.
为评估美托洛尔对胰岛素敏感性及昼夜血浆激素水平的影响，对7名轻度高血压受试者进行了研究（4名男性和3名女性，年龄52±8岁，体重指数25.4±1.9，均值±标准差）。该研究采用安慰剂对照、双盲、交叉设计，美托洛尔治疗6周（100 mg，每日2次）与安慰剂对照。在每个治疗期结束时，连续采集24小时血样以分析激素水平的昼夜变化，并进行高胰岛素正葡萄糖钳夹试验并输注[3-3H]-D-葡萄糖。通过三种不同方法评估胰岛素敏感性：昼夜血浆胰岛素和葡萄糖水平；葡萄糖消耗；以及正葡萄糖钳夹试验条件下的胰岛素敏感性指数。安慰剂治疗和美托洛尔治疗后，空腹血糖和胰岛素浓度以及胰岛素、生长激素、睾酮和皮质醇的平均血浆昼夜水平相似，而美托洛尔治疗后去甲肾上腺素和肾上腺素水平显著升高。在钳夹试验期间，美托洛尔治疗后血浆胰岛素显著高于安慰剂治疗后（56±3对64±2 mU L(-1)，P<0.05）。因此，美托洛尔治疗后胰岛素敏感性指数[葡萄糖输注率（GIR）/血浆胰岛素]较低（16.1±2.6对10.2±1.2，P<0.05），尽管GIR没有显著变化。我们认为，胰岛素敏感性指数可能无法准确反映胰岛素作用，因为在胰岛素输注期间血浆胰岛素水平显著升高，但在24小时时未升高，这可能是由于外源性胰岛素分布和/或降解速率的改变。因此，美托洛尔在高血压受试者中诱导胰岛素抵抗的可能性可能比之前认为的要小。
