THE EFFECT OF METOPROLOL TREATMENT ON INSULIN SENSITIVITY AND DIURNALPLASMA-HORMONE LEVELS IN HYPERTENSIVE SUBJECTS

To evaluate the effect of metoprolol on insulin sensitivity and diurna l plasma hormone levels, seven mildly hypertensive subjects were inves tigated (four men and three women, age 52 +/- 8, body mass index 25.4 +/- 1.9, mean +/- SD). The study had a placebo-controlled, double-blin d, 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 we re collected continuously for diurnal analysis of hormone levels and a hyperinsulinaemic euglycaemic clamp combined with [3-H-3]-D-glucose i nfusion was performed. Insulin sensitivity was evaluated by means of t hree different methods: diurnal plasma insulin and glucose levels; glu cose consumption; and insulin sensitivity index during euglycaemic cla mp conditions. Fasting blood glucose and insulin concentrations as wel l as mean plasma diurnal levels of insulin, growth hormone, testostero ne and cortisol were similar after placebo and metoprolol treatment, w hereas noradrenaline and adrenaline levels were significantly increase d 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 sensit ivity index [glucose infusion rate (GIR)/plasma insulin] was lower aft er metoprolol treatment (16.1 +/- 2.6 vs. 10.2 +/- 1.2, P < 0.05), alt hough GIR was not significantly changed. We suggest that the insulin s ensitivity index may not accurately reflect the insulin effect as the plasma level of insulin was significantly increased during insulin inf usion 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.