title: Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes.
abstract: Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when beta-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol.
authors.affiliation: Rush University Medical Center, Chicago, IL 60612, USA. gbakris@earthlink.net
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.forename: Richard E
authors.initials: RE
authors.lastname: Katholi
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: Franz
authors.initials: F
authors.lastname: Messerli
authors.forename: Robert A
authors.initials: RA
authors.lastname: Phillips
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
authors.forename: Brian
authors.initials: B
authors.lastname: Waterhouse
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Lukas
authors.forename: Karen M
authors.initials: KM
authors.lastname: Anderson
authors.forename: David S H
authors.initials: DS
authors.lastname: Bell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D001794:Blood Pressure; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000652:urine*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D011412:Propanolamines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D003404:Creatinine; D008790:Metoprolol