Document Detail


Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives.
MedLine Citation:
PMID:  20498618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Thiazide diuretics can impair glucose metabolism and increase new-onset diabetes. Adding an angiotensin receptor blocker to diuretics may protect against these metabolic effects; however, the mechanism of this protection is unclear.
METHOD: To explore potential mechanisms, a 16-week multicenter trial was conducted to ascertain the relative glucose metabolism effects of combined hydrochlorothiazide and angiotensin receptor blocker (valsartan) therapy compared with hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive individuals (BMI = 35 +/- 7 kg/m, seated BP = 159 +/- 8/94 +/- 8 mmHg, and mean age 56 years). Individuals were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 mg or hydrochlorothiazide, with titration to hydrochlorothiazide 25 mg and amlodipine 10 mg, respectively. Changes from baseline to week 16 in fasting and 2-h postprandial glucose and insulin levels after an oral glucose load were measured.
RESULTS: At week 16, clinic blood pressure reductions were similar (P > 0.05) in both groups. Fasting and 2-h glucose levels increased (P < 0.05) with the amlodipine combination but not with the valsartan combination. In concert with these glucose responses, postprandial insulin increases from baseline were substantially greater with valsartan than with amlodipine plus hydrochlorothiazide group (P = 0.001). The glucose responses were inversely related to insulin responses at the study conclusion.
CONCLUSION: The novel observation of this investigation was that the combination of valsartan and hydrochlorothiazide was associated with greater glucose-stimulated insulin secretory and lesser glycemic excursion responses than the amlodipine combination group. Thus, this data suggests that adding an angiotensin receptor blocker attenuates the negative effects of thiazides on pancreatic beta-cell glucose-induced insulin secretion.
Authors:
James R Sowers; Leopoldo Raij; Ishwaral Jialal; Brent M Egan; Elizabeth O Ofili; Rita Samuel; Dion H Zappe; Das Purkayastha; Prakash C Deedwania
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-21     Completed Date:  2010-11-12     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1761-9     Citation Subset:  IM    
Affiliation:
Diabetes and Cardiovascular Center, University of Missouri School of Medicine, and VA Medical Center, Columbia, Missouri 65212, USA. sowersj@health.missouri.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00439738
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MeSH Terms
Descriptor/Qualifier:
Aged
Amlodipine / pharmacology
Angiotensin II Type 1 Receptor Blockers / therapeutic use*
Blood Glucose / analysis
Blood Pressure / drug effects
Body Mass Index
Calcium Channel Blockers / pharmacology
Diuretics / therapeutic use*
Drug Therapy, Combination
Female
Glucose Tolerance Test
Humans
Hydrochlorothiazide / therapeutic use*
Hypertension / blood,  drug therapy*,  physiopathology
Insulin / blood
Male
Middle Aged
Obesity*
Tetrazoles / therapeutic use*
Treatment Outcome
Valine / analogs & derivatives*,  therapeutic use
Grant Support
ID/Acronym/Agency:
R01 HL073101-05A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Blood Glucose; 0/Calcium Channel Blockers; 0/Diuretics; 0/Tetrazoles; 11061-68-0/Insulin; 137862-53-4/valsartan; 58-93-5/Hydrochlorothiazide; 7004-03-7/Valine; 88150-42-9/Amlodipine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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