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


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
Current Controlled Trials NCT00497003.
Kveiborg
Britt
B
Department of Medicine, Naestved Hospital, Naestved, Denmark. BRIKVE01@geh.regionh.dk
Hermann
Thomas S
TS
Major-Pedersen
Atheline
A
Christiansen
Buris
B
Rask-Madsen
Christian
C
Raunsø
Jakob
J
Køber
Lars
L
Torp-Pedersen
Christian
C
Dominguez
Helena
H
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D017156:Photoplethysmography; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D012039:Regional Blood Flow; D012701:Serotonin / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D007004:Hypoglycemic Agents; D007328:Insulin; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D009599:Nitroprusside; D012701:Serotonin; D008790:Metoprolol