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

Britt Kveiborg, Thomas S Hermann, Atheline Major-Pedersen, Buris Christiansen, Christian Rask-Madsen, Jakob Raunsø, Lars Køber, Christian Torp-Pedersen, Helena Dominguez, Britt Kveiborg, Thomas S Hermann, Atheline Major-Pedersen, Buris Christiansen, Christian Rask-Madsen, Jakob Raunsø, Lars Køber, Christian Torp-Pedersen, Helena Dominguez

Abstract

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.

Figures

Figure 1
Figure 1
Endothelial function presented as relative forearm blood-flow at baseline was lower in the group of patients with type 2 diabetes, compared to the healthy control group. Forearm blood-flow is presented as a proportion between the infused and the non-infused arm.
Figure 2
Figure 2
At baseline, serotonin-stimulated forearm blood flow was enhanced by insulin in the healthy control group while this response was blunted in patients with type 2 diabetes.
Figure 3
Figure 3
Forearm blood-flow was not changed in the group of patients with type 2 diabetes after treatment with carvedilol (white circle) compared to the response before treatment (black circle).
Figure 4
Figure 4
Forearm blood-flow was not changed in the group of patients with type 2 diabetes after treatment with metoprolol (white circle) compared to the response before treatment (black circle).
Figure 5
Figure 5
The percentage increase in forearm blood-flow after co-infusion of serotonin and insulin was decreased after treatment with metoprolol (white triangle) compared to the blood-flow before this treatment (black triangle). The increase in forearm blood-flow was not changed by treatment with carvedilol.
Figure 6
Figure 6
Forearm blood-flow after stimulation with sodium nitroprusside was unchanged after treatment with carvedilol.
Figure 7
Figure 7
Forearm blood-flow after stimulation with sodium nitroprusside was unchanged after treatment with metoprolol.

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