Summary and conclusionsThe effects on diabetic control of the relative cardioselective beta-blocker metoprolol and the non-selective drug propranolol were compared in 20 hypertensive diabetic patients receiving diet alone or diet and oral hypoglycaemic agents. Each drug was given for one month in a double-blind, cross-over study. Fasting, noon, and mid-afternoon blood sugar concentrations rose by 1-0-1-5 mmol/l (18-27 mg/100 ml). The rise with propranolol was not significantly greater than with metoprolol. In a few patients the rise was clinically important.The small overall change observed in diabetic control should not deter the use of beta-blockers in non-insulindependent diabetics, provided control is carefully monitored at the onset of treatment. IntroductionCatecholamines play a part in the release of insulin' and in the clinical reaction to hypoglycaemia2 and metabolic recovery from it.3 Adrenoceptor-blocking drugs might therefore be expected to influence the way in which patients, particularly diabetics, respond to fluctuations in blood sugar concentrations. Studies on volunteers4-6 show that beta-blockers modify the recovery from hypoglycaemia and suggest that selective, beta1-blocking drugs interfere less than non-selective drugs. The possible metabolic effects of beta-blockers in the presence of a high blood sugar concentration, however, have received relatively little attention, though one study7 showed that glucose tolerance is impaired to a greater extent with non-selective than cardioselective betablockers. One explanation for these results is that insulin secretion may be influenced through a beta 2-receptor in man as it is in dogs.8 The relevance of these observations to the routine management of diabetes is unknown.We decided to see whether long-term treatment with a betablocker materially affects blood sugar control in maturity-onset diabetes and if any advantage is gained from choosing a cardioselective agent. With these aims we compared the relatively cardioselective beta-blocker metoprolol9 with the non-selective agent propranolol in patients with maturity-onset diabetes.

SUMMARYSerum prolactin (PRL) was used as a hormone marker of serotoninergic function following oral administration of an acute dose of a serotoninergic agonist. Five male endurance-trained athletes (ET) and five healthy non-endurance-trained controls (NT) were studied. The peak PRL concentration was lower (P = 0.031) for the ET athletes (486±208 mU 1-'; mean±S.D.) than for the NT controls (1000±385 mU 1-1); the total release of PRL was also lower (P = 0-042) for the ET subjects. The lower neuroendocrine response to a serotoninergic agonist in the endurance-trained athletes suggests a downregulation of central serotoninergic receptor function in response to endurance training in man. INTRODtJCTION

Objective-To measure the previously reported ; blocker induced adverse changes in mood state and anxiety measures, and to determine ifprolonged aerobic exercise attenuates such mood modifications. Methods-After 4 days of drug treatment with comparable doses of propranolol (40 and 80 mg), metoprolol (50 and 100 mg), or placebo, mood (POMS) and anxiety states (STAI) were assessed in healthy volunteers, before and after 1 h of treadmill walking exercise at 50% maximum oxygen uptake. Results-Compared to placebo, resting "tension", "depression", and "total mood disturbance" were significantly higher on propranolol 80 mg, but all were reduced with exercise. "Fatigue" and "confusion" were also higher on propranolol, and were unaffected by exercise. "Fatigue" was also higher than placebo after exercise on metoprolol 100 mg. "Anxiety" was unaffected by drug treatment or exercise. Conclusions-The evidence that ; blockers, and particularly propranolol, have adverse effects on mood was confirmed. It would be preferable to prescribe a 1 blocker which does not adversely alter mood states. However, exercise significantly reduced the measures of "tension" and "depression" which were adversely increased by propranolol. Exercise prescription may therefore not only be compatible with 1 blockade, but a highly desirable adjuvant therapy. (BrJt Sports Med 1996;30:238-242)

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Objective-Previous studies have shown that P, selective agents have fewer adverse effects on exercise metabolism than nonselective P blockers, and this has been attributed to their reduced blockade of P2receptors. This study aimed at determining whether a P blocker with partial agonist activity at P1 and P2 receptors (celiprolol) was better than a conventional P, receptor-blocker (atenolol) in prolonging exercise capabilities. Methods-After four days of treatment with celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. Results-Mean exercising heart rate was significantly lower in those taking either of the P blockers than in those taking placebo, and significantly lower for those taking atenolol rather than celiprolol. Fat oxidation was significantly lower for those taking celiprolol (38.8 regularly. However, we did not detect significant differences between atenolol and celiprolol in overall mean fat oxidation or perceived exertion in this study. (BrJ Sports Med 1997;31:120-125) Keywords: atenolol; celiprolol; exercise; 1B blockade; fat oxidation Prolonged aerobic exercise`-5 and 1 blockade6 7 both have important roles in the prevention and management of cardiovascular disease. However, fatigue is a commonly reported side effect of P blockade, and may be due to reduced cardiac output, reduced liver and muscle glycogenolysis, and reduced lipolysis,89 all of which may reduce the capacity for exercise to some degree.As the therapeutic effects of 3 blockers are due to their f, receptor blocking properties, some reduction in adipose lipolysis (f3 and 12 mediated)'0 11 must remain an unavoidable side effect of 01 receptor blockade.Celiprolol is a selective 1 receptor blocker'2 13 with some partial agonist activity at both ,13 and P2 receptors.'4 The purpose of this study was to examine exercise metabolism, and particularly fat oxidation, during submaximal exercise preceded by four days' oral administration of a ,1 selective drug (atenolol), a 13 selective drug with 12 agonist properties (celiprolol), or placebo. Method SUBJECTSTwenty four healthy subjects (12 male, 12 female, body mass index _ 32) underwent a routine medical examination and a blood test. No abnormalities were found. Two subjects (one male, one female) were later excluded from the trial when it was discovered that they were taking previously undisclosed drugs. The remaining 22 subjects then carried out a fitness test (constant speed and increasing gradient protocol, two minute stages until exhaustion) to measure maximal oxygen uptake (Vo2 max). Subjects were non-specifically trained with a Vo2 max of less than 60 ml/kg/min. On another day, a habituation walk was completed on a motorised treadmill at a speed and gradient...