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Publications (2)5.18 Total impact

  • Article: Effects of Exenatide vs. Metformin on endothelial function in obese patients with pre-diabetes: a randomized trial.
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    ABSTRACT: Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. This study is registered on http://www.clinicaltrials.gov/: NCT00546728.
    Cardiovascular Diabetology 06/2012; 11:64. · 3.35 Impact Factor
  • Article: Carvedilol-lisinopril combination therapy and endothelial function in obese individuals with hypertension.
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    ABSTRACT: The authors hypothesized that carvedilol controlled-release plus lisinopril combination therapy (C+L) would increase endothelial function and decrease oxidative stress to a greater extent than hydrochlorothiazide plus lisinopril combination therapy (H+L) in obese patients with hypertension. Twenty-five abdominally obese patients (aged 54.4±7.3 years; 14 women) with hypertension/prehypertension were enrolled in a 7-month (two 3-month treatment periods separated by a 1-month washout), randomized, double-blind, controlled, crossover clinical trial comparing C+L vs H+L. Endothelial function, measured by digital reactive hyperemic index (RHI), circulating oxidized low-density lipoprotein (oxLDL), 8-isoprostane, and asymmetric dimethylarginine (ADMA) were obtained at baseline, post-period 1, post-washout, and post-period 2. Analyses were adjusted for baseline measurements by analysis of covariance, with robust variance estimation for confidence intervals and P values. C+L treatment compared to H+L treatment significantly improved RHI (0.74, 95% confidence interval, 0.31-1.19, P =.001). This difference persisted after adjustment for the change in systolic blood pressure. No significant treatment differences were observed for oxLDL, 8-isoprostane, or ADMA. These data provide evidence that independent of blood pressure-lowering, C+L therapy improves endothelial function to a greater extent than H+L therapy. Levels of oxidative stress were not significantly different between treatments, suggesting that other mechanisms may be responsible for the improvement in endothelial function.
    Journal of Clinical Hypertension 02/2012; 14(2):85-91. · 1.83 Impact Factor