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Borghetto Santo Spirito, Italy

Perlstein T.S.,Harvard University | Henry R.R.,University of California at San Diego | Mather K.J.,Indiana University | Rickels M.R.,University of Pennsylvania | And 7 more authors.
Clinical Science | Year: 2012

AngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multicentre trial of 8 weeks duration. We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity (expressed as the 'M/I' value) and RH-PAT (reactive hyperaemiaperipheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic β-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F 2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic β-cell function. © The Authors Journal compilation © 2012 Biochemical Society. Source


McDonough C.W.,University of Florida | Burbage S.E.,University of Florida | Duarte J.D.,University of Illinois at Chicago | Gong Y.,University of Florida | And 10 more authors.
Journal of Hypertension | Year: 2013

OBJECTIVE:: Single-nucleotide polymorphisms (SNPs) in NEDD4L may influence the ability of the NEDD4L protein to reduce epithelial sodium channel expression. A variant in NEDD4L, rs4149601, was associated with antihypertensive response and cardiovascular outcomes during treatment with thiazide diuretics and β-blockers in a Swedish population. We sought to further evaluate associations between NEDD4L polymorphisms, blood pressure response and cardiovascular outcomes with thiazide diuretics and β-blockers. METHODS:: Four SNPs, rs4149601, rs292449, rs1008899 and rs75982813, were genotyped in 767 patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trial and association was assessed with blood pressure response to hydrochlorothiazide and atenolol. One SNP, rs4149601, was also genotyped in 1345 patients from the International Verapmil SR Trandolapril Study (INVEST), and association was examined with adverse cardiovascular outcomes relative to hydrochlorothiazide treatment. RESULTS:: Significant associations or trends were found between rs4149601, rs292449, rs75982813 and rs1008899 and decreases in blood pressure in whites on hydrochlorothiazide, and a significant association was observed with increasing copies of the GC rs4149601-rs292449 haplotype and greater blood pressure response to hydrochlorothiazide in whites (P = 0.0006 and 0.006, SBP and DBP, respectively). Significant associations were also seen with rs4149601 and an increased risk for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide [P = 0.022, odds ratio (95% confidence interval) = 10.65 (1.18-96.25)]. CONCLUSION:: NEDD4L rs4149601, rs292449 and rs75982813 may be predictors for blood pressure response to hydrochlorothiazide in whites, and NEDD4L rs4149601 may be a predictor for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide. © 2013 Lippincott Williams & Wilkins, Inc. Source


Pedrosa C.,University of Porto | Correia F.,University of Porto | Oliveira B.M.,University of Porto | Simeos-Pereira C.,Diabetes and Nutrition | Vaz-De-Almeida M.D.,University of Porto
Public Health Nutrition | Year: 2011

Objective To estimate the prevalence of overweight and obesity in schoolchildren from Aveiro, Portugal, according to two criteria: the International Obesity Task Force (IOTF) and the US Centers for Disease Control and Prevention (CDC) cut-offs.Design Weight, height and waist circumference were measured. Using the BMI, gender-and age-specific prevalences of overweight and obesity were determined according to the IOTF cut-offs extrapolated from an adult BMI of 25 and 30 kg/m2 and the CDC cut-off values of 85th and 95th BMI percentile.Setting Aveiro, Portugal.Subjects A random representative sample of 905 children (457 boys; 448 girls) aged 7-9 years.Results The prevalence of excess weight (overweight and obesity) was lowest according to IOTF cut-offs compared to CDC (281 % v. 312 %), especially obesity (81 % v. 140 %). However, the CDC and IOTF criteria have a strong agreement (Cohens k = 0755; P < 0001). There were significant differences in excess weight between boys and girls according to the CDC (269 % v. 357 %; P = 0003). Obese children are younger and the majority present abdominal obesity.Conclusions The present study shows a high prevalence of excess weight in Aveiro children, similar to other Portuguese regions and among the highest in Europe, especially in the female gender. The IOTF cut-off values give a lower prevalence of excess weight, namely obesity. © 2009 The Authors. Source


Hocher B.,University of Potsdam | Hocher B.,Institute of Pharmacology | Heiden S.,Institute of Pharmacology | von Websky K.,University of Potsdam | And 10 more authors.
PLoS ONE | Year: 2011

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05), especially in those receiving furosemide (-41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis. © 2011 Hocher et al. Source


Wojtusciszyn A.,Diabetes and Nutrition | Wojtusciszyn A.,Institute of Research in Biotherapies
Diabetic Hypoglycemia | Year: 2012

A 39-year-old woman with type 1 diabetes since 1995 had been treated with continuous subcutaneous insulin infusion since a pregnancy in 1997. She had developed lymphocytic hypophysitis postpartum, which had been thought to have resolved spontaneously. She had no complications of diabetes but had developed impaired awareness of hypoglycaemia (IHA) and frequently experienced episodes of severe hypoglycemia requiring assistance. Clinical recommendations to adjust insulin doses were followed meticulously by the patient. At initial review, pituitary function superficially appeared to be normal, with normal plasma concentrations of gonadotrophins, thyroid-stimulating hormone and cortisol, and a normal response to a 250 μg synacthen test. However, plasma insulin-like growth factor-1 was low (26 ng/ml). Pituitary magnetic resonance imaging was normal. An insulin-induced hypoglycemia test showed a total absence of responses of growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol. A GH-releasing hormone test confirmed the presence of GH deficiency and a 1 μg synacthen test revealed adrenal insufficiency. Replacement therapy with GH and hydrocortisone was therefore recommended. Although the present case illustrates the role of subclinical hypopituitarism in provoking recurrent hypoglycemia, cortisol and GH insufficiencies may co-exist in people with diabetes who have IHA, and may need to be actively sought through testing of pituitary function. Source

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