The effect of short – term exercise on nitric oxide (NO) serum concentrations in overweight and obese women

Objective: The aims of the present study was to examine the effect of overweight and obesity on serum concentrations of nitric oxide metabolites and evaluate the differences of exercise induced NO production in obese and lean women. Materials and Methods: The study groups consisted of 154 women including 102 obese and 24 overweight patients and 28 lean controls. Serum concentrations of nitric oxide metabolites were measured before and after exercise with the use of ELISA kits. The serum concentrations of lactate before and after exercise were measured with the use of strip test (ACCUSPORT analyzer). Serum concentration of insulin was measured with the use of RIA. Plasma glucose, cholesterol, HDL cholesterol and triglicerydes were determined by enzymatic procedure. Impedance analysis (Bodystat) was used to determine body composition. Results: Serum concentration of NO in overweight group and obese group was significantly higher when compared to controls, p<0.05 and p<0.01, respectively. There was no difference in levels of NO between overweight and obese groups .During exercise NO concentrations increased significantly in all groups and the post- exercise levels did not differ statistically in overweight and obese groups from that in controls. The value of NO was the lowest in obese group but there were no significant differences between obese, overweight and control groups. Conclusions: Obesity may attenuate the exercise - induced endothelial NO release

The effect of weight loss on serum concentrations of nitric oxide induced by short - term exercise in obese women

Objective: The aim of present study was to examine the effect of weight loss comprising regular moderate physical activity on resting serum concentrations of nitric oxide metabolites and exercise induced NO release. Materials and Methods: The study was carried out in 43 obese women without additional diseases (age 41.8±11.9y, body weight 94.5±15.1kg, BMI 36.5±4.6kg/m2). All obese patients participated in a 3-month weight reduction programme that consisted of 1) a group instruction in behavioural and dietary methods of weight control every two weeks; 2) 1000-1400kcal/day balanced diet, and 3) moderate physical exercises (30 minutes, 3 times a week). Before and after treatment body mass and height were measured, body mass index (BMI) was calculated. Body composition was determined by impedance analysis using a Bodystat analyser. The serum concentration of nitric oxide metabolites before and after exercise was measured using spectrophotometry method by Griess. The serum concentrations of lactate before and after exercise were measured with the use of strip test (ACCUSPORT analyzer). Serum concentration of insulin was measured with the use of RIA. Plasma glucose, cholesterol, HDL cholesterol and triglicerydes were determined by enzymatic procedure. Results: The mean weight loss during treatment was 8.3±4.3 kg. We did not observe differences between resting serum concentrations of NO and lactate before and after weight loss. During exercise serum NO concentrations increased significantly both before and after weight loss treatment. After the weight reduction treatment, the time of exercise test increased significantly P<0.005, but there were no significant differences between the value of NO before and after weight loss. Conclusion: 3 – month regular physical activity and weight loss did not influence exercise-induced nitric oxide production

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older

Purpose Elevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older. Methods The study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured. Nutritional status (BMI/waist circumference) and treatment with statins and fibrates were evaluated. Glomerular filtration rate (eGFR), de Ritis ratio, and fatty liver index (FLI), as well as HOMA-IR were calculated. Results Our study revealed a strong relationship between components of MS and RBP4 in both sexes: plasma RBP4 levels were increased in men by at least 3×, and in women by at least 4×. Hypertriglyceridemia was most strongly associated with elevated plasma RBP4 levels. Multivariate, sex-adjusted regression analysis demonstrated that chronic kidney disease [OR 1.86 (95% CI 1.78-1.94)], hypertriglyceridemia [OR 1.52 (1.24-1.87)], hypertension [OR 1.15 (1.12-1.19)], low serum HDL cholesterol [OR 0.94 (0.92-0.97)], and age > 80 years [OR 0.86 (0.81-0.90)] were each independently associated with RBP4 concentration (all p < 0.001). Conclusions In Caucasians 65 years and older, RBP4 serum levels are associated with a number of components of MS, independent of sex and kidney function. Hypertriglyceridemia as a component of MS is most signifcantly related to RBP4 concentration

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background Liraglutide 3\ub70 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3\ub70 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2\ub77 times longer with liraglutide than with placebo (95% CI 1\ub79 to 3\ub79, p<0\ub70001), corresponding with a hazard ratio of 0\ub721 (95% CI 0\ub713\u20130\ub734). Liraglutide induced greater weight loss than placebo at week 160 (\u20136\ub71 [SD 7\ub73] vs 121\ub79% [6\ub73]; estimated treatment difference 124\ub73%, 95% CI 124\ub79 to 123\ub77, p<0\ub70001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3\ub70 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark