Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study.

AIM: Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin-stimulated endothelial function in patients with type 2 diabetes. METHOD: 24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily. Endothelium-dependent vasodilation was assessed by using venous occlusion plethysmography with increasing doses of intra-arterial infusions of the agonist serotonin. Insulin-stimulated endothelial function was assessed after co-infusion of insulin for sixty minutes. Vaso-reactivity studies were done before and after the two-month treatment period. RESULTS: Insulin-stimulated endothelial function was deteriorated after treatment with metoprolol, the percentage change in forearm blood-flow was 60.19% +/- 17.89 (at the highest serotonin dosages) before treatment and -33.80% +/- 23.38 after treatment (p = 0.007). Treatment with carvedilol did not change insulin-stimulated endothelial function. Endothelium-dependent vasodilation without insulin was not changed in either of the two treatment groups. CONCLUSION: This study shows that vascular insulin sensitivity was preserved during treatment with carvedilol while blunted during treatment with metoprolol in patients with type 2 diabetes. TRIAL REGISTRATION: Current Controlled Trials NCT00497003.

Carvedilol in the treatment of chronic heart failure: lessons from the Carvedilol Or Metoprolol European Trial.

Beta-blockers have been shown to improve survival in patients with chronic heart failure. The effect of different generations of beta blockers has been debated. Both metoprolol and carvedilol have demonstrated beneficial effects in placebo-controlled trials. In The Carvedilol Or Metoprolol European Trial (COMET) two beta blockers were compared in a double-blind randomized matter. This is the first direct comparison between metoprolol and carvedilol of long-term effect on survival in patients with chronic heart failure. The all-cause mortality was significantly reduced in the favour of carvedilol. The dose and formulation of metoprolol used in this trial has caused debate, and it has been questioned whether a similar beta1-blockade is obtained in the two intervention groups. At this time there is an unresolved debate as to whether carvedilol is a superior beta-blocker or whether differences in beta1-blockade explained the results of COMET.

Metabolic effects of beta-adrenoceptor antagonists with special emphasis on carvedilol.

Although beta-adrenoceptor antagonists (beta-blockers) have effects on metabolism via their mechanism as blockers of adrenergic stimulation, most interest in the metabolic effects of beta-blockers is caused by their effect on glucose metabolism. Strict metabolic control and management of cardiovascular risk factors in patients with diabetes mellitus has proven to be of great importance in the improvement of prognosis. Beta-blockers are necessary tools for the treatment of heart failure and hypertension. The use of beta-blockers in patients with diabetes mellitus has been controversial because of fear of deterioration of metabolic control of glucose and lipids and blunting of the symptoms of hypoglycemia. Currently, it appears that there is a beneficial metabolic effect with the third-generation beta-blocker carvedilol. Comparisons have been made between the second-generation beta-blocker metoprolol and carvedilol, with a clear advantage for carvedilol in terms of metabolic control. In the GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives) trial, a decrease of 9.1% (p = 0.004) in insulin resistance, compared with baseline values, was seen in patients treated with carvedilol, whereas no significant difference was seen in the group of patients treated with metoprolol. Additionally, an increase in glycosylated hemoglobin of 0.15% from baseline was seen in the metoprolol group (p < 0.001) compared with no significant change in the carvedilol group. These findings indicate that, as carvedilol exerts favorable effects on glucose metabolism compared with metoprolol, patients with diabetes mellitus could benefit from treatment with carvedilol rather than metoprolol. The mechanisms behind these findings are not yet fully understood. Several mechanisms have been suggested, and special interest has been paid to the investigation of the potential beneficial role of the beta2- and alpha1-adrenoceptor-blocking effects of carvedilol, along with its known antioxidant properties.

Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension.

UNLABELLED: Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would be the case in humans suffering from essential hypertension. METHODS: 40 hypertensive individuals without diabetes and with normal levels of cholesterol were examined. The participants were randomized either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates with high in vitro antioxidative potential, for a 4 week period or to continue their ordinary diet and act as controls. Blood pressure, endothelial function measured by flow mediated dilation (FMD) and blood samples were obtained from the participants every other week and the content of glucosinolates was measured before and after the study. Measurements were blinded to treatment allocation. RESULTS: In the interventional group overall FMD increased from 4% to 5.8% in the interventional group whereas in the control group FMD was stable (4% at baseline and 3.9% at the end of the study). The change in FMD in the interventional group was mainly due to a marked change in FMD in two participants while the other participants did not have marked changes in FMD. The observed differences were not statistically significant. Likewise significant changes in blood pressure or blood samples were not detected between or within groups. Diastolic blood pressure stayed essentially unchanged in both groups, while the systolic blood pressure showed a small non significant decrease (9 mm Hg) in the interventional group from a value of 153 mm Hg at start. CONCLUSION: Daily ingestion of 10 g dried broccoli sprouts does not improve endothelial function in the presence of hypertension in humans. TRIAL REGISTRATION: Clinicaltrials.gov NCT00252018.