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Aims: To determine the impact of smoking and alcohol exposure during adolescence on arterial stiffness at 17 years., Methods and Results: Smoking and alcohol use were assessed by questionnaires at 13, 15, and 17 years in 1266 participants (425 males and 841 females) from the ALSPAC study. Smoking status (smokers and non-smoker) and intensity ('high' ≥100, 'moderate' 20-99, and 'low or never' <20 cigarettes in lifetime) were ascertained. Participants were classified by frequency (low or high) and intensity of drinking [light (LI <2), medium (MI 3-9), and heavy (HI >10 drinks on a typical drinking day)]. Carotid to femoral pulse wave velocity (PWV) was assessed at 17 years [mean ± standard deviation and/or mean difference (95% confidence intervals)]. Current smokers had higher PWV compared with non-smokers (P = 0.003). Higher smoking exposure was associated with higher PWV compared with non-smokers [5.81 ± 0.725 vs. 5.71 ± 0.677 m/s, mean adjusted difference 0.211 (0.087-0.334) m/s, P = 0.001]. Participants who stopped smoking had similar PWV to never smokers (P = 0.160). High-intensity drinkers had increased PWV [HI 5.85 ± 0.8 vs. LI 5.67 ± 0.604 m/s, mean adjusted difference 0.266 (0.055-0.476) m/s, P = 0.013]. There was an additive effect of smoking intensity and alcohol intensity, so that 'high' smokers who were also HI drinkers had higher PWV compared with never-smokers and LI drinkers [mean adjusted increase 0.603 (0.229-0.978) m/s, P = 0.002]., Conclusion: Smoking exposure even at low levels and intensity of alcohol use were associated individually and together with increased arterial stiffness. Public health strategies need to prevent adoption of these habits in adolescence to preserve or restore arterial health.

Background: Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages - nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, whilst maintaining statistical power and ability for causal inference., Methods: In this study, we used a combination of conventional multivariable regression analysis, Mendelian randomization (MR) and sub-sample RbG methodologies to estimate the causal effect of BMI on gross-level and detailed cardiovascular health in healthy participants from the Avon Longitudinal Study of Parents and Children at age 17 (N=1420-3108 for different outcomes) and an independent sample from the same cohort (for RbG) study at age 21 (N=386-418)., Results: In both MR and RbG analyses, results suggested that higher BMI causes higher blood pressure (BP) and left ventricular mass index (LVMI) in young adults (e.g., difference in LVMI per kg/m 2 using MR: 1.07g/m 2.7 ; 95% CI: 0.62, 1.52; P =3.87x10 -06 and per 3.58kg/m 2 using RbG: 1.65g/m 2.7 95% CI: 0.83, 2.47; P =0.0001). Additionally, RbG results suggested a causal role of higher BMI on higher stroke volume (SV: difference per 3.58kg/m 2 : 1.49ml/m 2.04 ; 95% CI: 0.62, 2.35; P =0.001) and cardiac output (CO: difference per 3.58kg/m 2 : 0.11l/min/m 1.83 ; 95% CI: 0.03, 0.19; P =0.01) but no strong evidence for a causal role on systemic vascular resistance or total arterial compliance. Neither analysis supported a causal role of higher BMI on heart rate., Conclusions: Complementary MR and RbG causal methodologies, together with a range of sensitivity analyses, suggest that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. Higher BMI also resulted in increased CO in the RbG study, which appeared to be solely driven by SV, as neither MR nor RbG analyses suggested a causal effect of BMI on heart rate. These consistent results support efforts to reduce BMI from a young age to prevent later adverse cardiovascular health and illustrate the potential for phenotypic resolution with maintained analytical power using RbG.

The purpose of this paper was to identify and summarize current evidence describing periodontal complications associated with obesity. Electronic searches supplemented with manual searches were carried out to identify relevant systematic reviews. Identification, screening, eligibility, and inclusion of studies were performed independently by two reviewers. A MeaSurement Tool to Assess systematic Reviews (AMSTAR) was used to assess the quality and risk of bias of the included reviews. From 430 titles and abstracts screened, 14 systematic reviews were considered as eligible for inclusion in this meta-review. Eight reviews reported on cross-sectional studies investigating the association of obesity and periodontal diseases, 4 included longitudinal studies, 5 addressed response to periodontal therapy, 5 reported on studies investigating biomarkers, and only 2 were related to pediatric population samples. Systematic review summaries in the various study design domains (cross-sectional, longitudinal and experimental) report that obese individuals are more likely to have periodontal diseases, with more severe periodontal conditions, than nonobese individuals, with cross-sectional evidence congruent with longitudinal studies showing that obesity or weight gain increases the risk of periodontitis onset and progression. Published research on the effect of obesity on responses to periodontal therapy, or systemic or local biomarkers of inflammation, is variable and therefore inconclusive based on the evidence currently available, which suggests that overweight/obesity contributes to periodontal complications independently of other risk factors, such as age, gender, smoking, or ethnicity. This evidence supports the need for risk assessments for individual patients to facilitate personalized approaches in order to prevent and treat periodontal diseases., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

: Obesity predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke, which are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.

: Obesity is a key factor for cardiovascular diseases and complications. Obesity is associated with hypertension, dyslipidemia and type II diabetes, which are the major predictors of cardiovascular disease in the future. It predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke that are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.Epidemiology and mechanisms of obesity-induced hypertension, diabetes and dyslipidemia will be reviewed and the role of lifestyle modification and treatment strategies in obesity will be updated and analyzed. The best treatment options for people with obesity, hypertension, diabetes and dyslipidemia will discussed.

Objective: The aim of this study was to explore the potential effects of diet-induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue., Methods: This single-arm exploratory study included 20 adults with BMI ≥ 30 kg/m 2 completing an 8-week, complete, low-energy liquid diet. Pre- and postintervention anthropometric measurements, fasting blood draws, and endoscopic examinations to procure colorectal biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF-1), C-reactive protein (CRP), and blood lipids were measured in serum, and tissue markers of apoptosis (M30), colonocyte proliferation (Ki-67), and insulin signaling (phospho-mTOR) were assessed using immunohistochemical staining., Results: Participants achieved substantial weight loss (mean = 13.56%). Mean concentrations of insulin, glucose, and cholesterol were significantly reduced (P < 0.05), but IGF-1 and CRP were not. Colorectal tissue expression of Ki-67 was significantly reduced (preintervention mean score = 7, postintervention mean score = 3.9, mean % change -43.8; P = 0.027). There were no significant changes in M30 or phospho-mTOR., Conclusions: Weight loss in individuals with obesity was associated with improvements in insulin sensitivity and blood lipid profiles and a significant reduction in tissue Ki-67 expression. This is one of the first studies to demonstrate potential cancer-relevant changes in colorectal tissue following weight loss achieved through diet., (© 2017 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).)

Aims: Weight loss is expected to improve glycaemic control in patients with diabetes or at high risk hereof. Sibutramine causes weight loss and is associated with an increased risk of myocardial infarction and stroke in high-risk patients. We examined the impact of sibutramine-induced weight loss on glycaemic control., Methods and Results: In total, 8192 obese patients with diabetes were randomized to sibutramine or placebo plus diet and exercise after a preliminary 6 weeks in which all patients received sibutramine. Patients were classified into four groups of weight change. A total of 1582 patients had a weight loss >5.7 kg; 2047 patients lost 3.7-5.7 kg; 2432 patients lost <3.7 kg, and 1875 patients gained weight. Patients on sibutramine lost slightly more weight than those on placebo (-0.2 kg on average, P < 0.0001). Mean blood glucose changes in the placebo group were -0.6 mmol/L (±3.1, P = 0.0002), -0.2  mmol/L (±2.7, P = 0.04), and -0.1  mmol/L (±3.0, P = 0.01) in the moderate, modest, and mild weight loss groups, respectively; in the weight gain group blood glucose levels increased by +0.2 mmol/L (±3.1, P = 0.003). Corresponding mean blood glucose changes in the sibutramine-treated patients were -0.4 mmol/L (±3.2, P = 0.0002), +0.1 mmol/L (±3.0, P = 0.04), +0.4 mmol/L (±2.8, P = 0.01), and +0.2 mmol/L (±3.4, P = 0.003). Mean values of HbA1c followed the same pattern though the HbA1c changes were smaller with weight loss and greater with weight gain in the sibutramine group. All results were statistically significant (P < 0.0001)., Conclusion: Weight loss induced by sibutramine, diet, and exercise attenuates falls in blood glucose levels and HbA1c compared with similar weight loss with placebo, diet, and exercise., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences., Objectives: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents., Search Methods: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions., Selection Criteria: We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants., Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information., Main Results: We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m 2 (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children., Authors' Conclusions: This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials.

Despite increasing prevalence of obesity, no country has successfully implemented comprehensive pathways to provide advice to all the severely obese patients that seek treatment. We aimed to formulate pathways for referral into and out of weight assessment and management clinics (WAMCs) that include internal medicine/primary care physicians as part of a multidisciplinary team that could provide specialist advice and interventions, including referral for bariatric surgery. Using a National Institute of Health and Care Excellence (NICE)-accredited process, a Guidance Development Group conducted a literature search identifying existing WAMCs. As very few examples of effective structures and clinical pathways existed, the current evidence base for optimal assessment and management of bariatric surgery patients was used to reach a consensus. The model we describe could be adopted internationally by health services to manage severely obese patients.

Background: Previous studies show that 'poor responders' to Roux-en-Y gastric bypass (RYGBP) may be identified on the basis of early postoperative weight loss. Early identification of poor responders could allow earlier provision of postoperative behavioural and/or intensive lifestyle interventions and enhance their maximal weight loss. Our aim was to investigate whether early postoperative weight loss predicts the maximal weight loss response after RYGBP and sleeve gastrectomy (SG)., Methods: We undertook a retrospective cross-sectional study of 1,456 adults who underwent either RYGBP (n = 918) or SG (n = 538) as a primary procedure in one of two European centres. Postoperative weight loss was expressed as weight loss velocity (WLV) and percentage weight loss. Linear regression analyses were performed to determine the association of early postoperative weight loss with maximal %WL, including adjustment for baseline variables., Results: There was marked variability in maximal %WL following both RYGBP (mean 32.9 %, range 4.1-60.9 %) and SG (mean 26.2 %, range 1.1-58.3 %). WLV 3-6 months postoperatively was more strongly associated with maximal %WL (r (2) = 0.32 for RYGBP and r (2) = 0.26 for SG, P < 0.001 for both) than either WLV 0-6 weeks or 6 weeks to 3 months postoperatively (r (2) = 0.14 and 0.10 for RYGBP, respectively; r (2) = 0.18 and 0.21 for SG, respectively; P < 0.001 for all). Multiple linear regression analysis, including baseline variables of age, sex, preoperative BMI, type 2 diabetes, ethnicity, and bariatric centre, revealed that 3-6 month WLV was an independent predictor of maximal %WL in both SG and RYGBP groups (standardised β-coefficients 0.51 and 0.52, respectively; P < 0.001 for both)., Conclusions: There is a marked variability in weight loss response following RYGBP and SG. Early postoperative weight loss can be used to identify patients whose predicted weight loss trajectories are suboptimal. Early targeting of poor responders with more intensive postoperative lifestyle and behavioural support could potentially enhance their weight loss response.

The management of obesity remains a major challenge. Dietary therapy often fails, whereas bariatric surgery, although successful, is demanding and applicable to a limited number of patients. Drug therapy has had many setbacks over the past 20 years because of serious adverse effects; however, several new drugs for the treatment of obesity are either licensed in some parts of the world, submitted for registration, or completing phase III trials. These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide, 3 mg), and new entities (lorcaserin). We discuss the challenges and opportunities for obesity pharmacotherapy and review in detail the efficacy of the new drugs regarding weight loss and both desirable and potential undesirable cardiovascular (CV) and metabolic risk factors. Substantial barriers remain, even if the drugs are approved, in successfully integrating these agents into weight management practice, largely related to cost, patient acceptability, and clinician willingness to be engaged in obesity treatment. Although hard clinical outcome benefit (at least for CV outcomes) has yet to be established, obesity pharmacotherapy may soon address many of the challenges in the clinical management of obesity, although newer and better drug combinations and more evidence of benefit from appropriately designed outcome trials is needed., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Lifestyle intervention programs after bariatric surgery have been suggested to maximise health outcomes. This pilot study aimed to investigate the feasibility and impact of an 8-week combined supervised exercise with nutritional-behavioral intervention following Roux-en-Y gastric bypass and sleeve gastrectomy., Methods: Eight female patients (44 ± 8 years old, BMI = 38.5 ± 7.2 kg m(-2)) completed the program. Before and after intervention, anthropometric measures, six-minute walk test (6MWT), physical activity level, eating behavior, and quality of life (QoL) were assessed. Percentage weight loss (%WL) outcomes were compared with a historical matched control group., Results: The program significantly improved functional capacity (mean increment in 6MWT was 127 ± 107 meters, p = 0.043), increased strenuous intensity exercise (44 ± 49 min/week, p = 0.043), increased consumption of fruits and vegetables (p = 0.034), reduced consumption of ready meals (p = 0.034), and improved "Change in Health" in QoL domain (p = 0.039). The intervention group exhibited greater %WL in the 3-12-month postsurgery period compared to historical controls, 12.2 ± 7.5% versus 5.1 ± 5.4%, respectively (p = 0.027)., Conclusions: Lifestyle intervention program following bariatric surgery is feasible and resulted in several beneficial outcomes. A large randomised control trial is now warranted.

Unlabelled: Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m(2)). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m(2), weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m(2)), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m(2) after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting., Learning Points: Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss follows a normal distribution with extremes of 'good' and 'poor' response.Profound anorexia and excessive weight loss post-SG may be associated with markedly elevated circulating fasted PYY and post-meal PYY and GLP1 levels.Octreotide treatment can produce symptomatic relief and weight regain for post-SG patients that have an extreme anorectic and weight loss response.The present case highlights the value of measuring circulating gut hormone levels in patients with post-operative anorexia and extreme weight loss.

Objective: To identify an early treatment milestone that optimizes sensitivity and specificity for predicting ≥5% weight loss at Week (W) 52 in patients with and without type 2 diabetes on lorcaserin or placebo., Methods: Post hoc area under the curve for receiver operating characteristic analyses of data from three phase 3 trials comparing lifestyle modification+placebo with lifestyle modification+lorcaserin. A total of 6897 patients (18-65 years; BMI, 30-45 or 27-29.9 kg/m(2) with ≥1 comorbidity) were randomized to placebo or lorcaserin 10 mg bid. Changes (baseline to W52) in cardiometabolic parameters were assessed., Results: Response (≥5% weight loss from baseline) at W12 was a strong predictor of W52 response. Lorcaserin patients with a W12 response achieved mean W52 weight losses of 10.6 kg (without diabetes) and 9.3 kg (with diabetes). Proportions achieving ≥5% and ≥10% weight loss at W52 were 85.5% and 49.8% (without diabetes), and 70.5% and 35.9% (with diabetes). Lorcaserin patients who did not achieve a W12 response lost 3.2 kg (without diabetes) and 2.8 kg (with diabetes) at W52. Responders had greater improvements in cardiometabolic risk factors than the modified intent-to-treat (MITT) population, consistent with greater weight loss., Conclusions: ≥5% weight loss by W12 predicts robust response to lorcaserin at 1 year., (Copyright © 2014 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).)

Background: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) are the most common bariatric procedures undertaken globally but there are no evidenced-based criteria that inform the selection of one operation over the other. The purpose of this study was thus to compare weight loss outcomes between RYGBP and SG, and to define patient factors affecting weight loss., Methods: A single-centre two-year follow-up retrospective cohort study of all adults who underwent either RYGBP (n = 422) or SG (n = 432) between 2007 and 2012, at University College London Hospitals National Health Service Foundation Trust, an academic tertiary referral centre, was undertaken. Multilevel linear regression was used to compare weight loss between groups, enabling adjustment for preoperative BMI (body mass index) and evaluation for interaction factors., Results: One- and two-year results showed that unadjusted BMI loss was similar between groups; 13.7 kg/m(2) (95% CI: 12.9, 14.6 kg/m(2)) and 12.8 kg/m(2) (95% CI: 11.8, 13.9 kg/m(2)) for RYGBP patients respectively compared with 13.3 kg/m(2) (95% CI: 12.0, 14.6 kg/m(2)) and 11.5 kg/m(2) (95% CI: 10.1, 13.0 kg/m(2)) for SG patients respectively. Adjusting for preoperative BMI, there was 2.2 kg/m(2) (95% CI: 1.5, 2.8) and 2.3 kg/m(2) (95% CI: 1.3, 3.3) greater BMI loss in the RYGBP group compared to the SG group at one and two years respectively (P < 0.001 for both). The interaction analyses demonstrated that age and sex had important differential impacts on SG and RYGBP weight outcomes. Men under 40 and women over 50 years obtained on average far less benefit from SG compared to RYGBP, whereas men over 40 years and women under 50 years experienced similar weight loss with either procedure (P = 0.001 and 0.022 for interaction effects at one and two years respectively)., Conclusions: Our results show that patient sex and age significantly impact on weight loss in a procedure-dependent manner and should be considered when choosing between RYGBP and SG. Optimizing procedure selection could enhance the effectiveness of bariatric surgery, thus further increasing the benefit-to-risk ratio of this highly effective intervention.

Aims: There is an increased risk of preterm and small-for-gestational-age births associated with bariatric surgery, especially if maternal early pregnancy body mass index (BMI) is <30.0kg/m(2). However, the relationship between timing of pregnancy post-bariatric surgery and effects on pregnancy outcome are unknown. The aim of this study was to investigate the timing of pregnancy post-bariatric surgery and compare early pregnancy BMI between women who became pregnant before or after the recommended 12month postoperative window., Methods/results: Women who underwent either sleeve gastrectomy or gastric bypass and subsequently became pregnant were offered antenatal care in a multidisciplinary high-risk clinic. There were 50 such pregnancies in women who attended our high-risk clinic (n=26 <12months and n=24 >12months postoperatively, mean estimated times to conception 31.9±12.6weeks and 102.8±37.7weeks respectively). There was no significant difference in early pregnancy BMI between groups (33.2±6.8kg/m(2) and 32.5+2.1kg/m(2) respectively, p=0.78). There were 6 miscarriages in each group, however more women in the <12month (n=8) than in the >12months group (n=2) were lost-to-follow-up (likelihood ratio 4.2, p=0.04)., Conclusions: Women who became pregnant <12months post-bariatric surgery were, for unknown reasons, less likely to attend follow-up in a specialist antenatal clinic than those who became pregnant >12months postoperatively. Further research is required to explore the relationship between timing of pregnancy post-bariatric surgery and pregnancy outcome and to identify predictors more clinically useful than early pregnancy BMI, in this high-risk pregnancy group., (Copyright © 2014.)

Public health initiatives focused on obesity prevention and lifestyle intervention programmes for patients with obesity have struggled to contain the obesity epidemic to date. In recent years, antiobesity drug therapies have had a limited role in clinical treatment algorithms for patients with obesity. Indeed, a number of high-profile antiobesity drug suspensions have markedly impacted upon the landscape of obesity pharmacotherapy. In this review, we discuss the advent of an increasing array of pharmacotherapeutic agents, which are effective both in inducing weight loss and in maintaining weight loss achieved by lifestyle measures. The development of these drugs as antiobesity agents has followed varying paths, ranging from lorcaserin, a selective serotonin agent, exploiting the beneficial central actions of fenfluramine but without the associated systemic side effects, to liraglutide, a gut hormone already used as a glucose-lowering drug but with appetite-suppressant properties, or the novel drug combination of phentermine/topiramate, two 'old' drugs used in lower doses than with previous therapeutic uses, resulting in an additive effect on weight loss and fewer side effects. We summarize the key findings from recent randomized controlled trials of these three drugs. Although these agents lead to clinically important weight loss when used as monotherapy, the use of antiobesity drugs as adjunctive therapy post intensive lifestyle intervention could prove to be the most successful strategy. Moreover, a progressive approach to obesity pharmacotherapy perhaps offers the best opportunity to finally address the obesity crisis on a mass scale.

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) reduces appetite and induces significant and sustainable weight loss. Circulating gut hormones changes engendered by LRYGBP are implicated in mediating these beneficial effects. Laparoscopic sleeve gastrectomy (LSG) is advocated as an alternative to LRYGBP, with comparable short-term weight loss and metabolic outcomes. LRYGBP and LSG are anatomically distinct procedures causing differential entero-endocrine cell nutrient exposure and thus potentially different gut hormone changes. Studies reporting the comparative effects of LRYGBP and LSG on appetite and circulating gut hormones are controversial, with no data to date on the effects of LSG on circulating peptide YY3-36 (PYY3-36) levels, the specific PYY anorectic isoform. In this study, we prospectively investigated appetite and gut hormone changes in response to LRYGBP and LSG in adiposity-matched non-diabetic patients. Anthropometric indices, leptin, fasted and nutrient-stimulated acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), PYY3-36 levels and appetite were determined pre-operatively and at 6 and 12 weeks post-operatively in obese, non-diabetic females, with ten undergoing LRYGBP and eight adiposity-matched females undergoing LSG. LRYGBP and LSG comparably reduced adiposity. LSG decreased fasting and post-prandial plasma acyl-ghrelin compared to pre-surgery and to LRYGBP. Nutrient-stimulated PYY3-36 and active GLP-1 concentrations increased post-operatively in both groups. However, LRYGBP induced greater, more sustained PYY3-36 and active GLP-1 increments compared to LSG. LRYGBP suppressed fasting hunger compared to LSG. A similar increase in post-prandial fullness was observed post-surgery following both procedures. LRYGBP and LSG produced comparable enhanced satiety and weight loss. However, LSG and LRYGBP differentially altered gut hormone profiles.

Objectives: To examine the effect that health professional (HP) advice to lose weight has on overweight and obese adults' motivation to lose weight and attempts to lose weight., Design: Cross-sectional survey., Setting: Great Britain., Participants: 810 overweight or obese (body mass index ≥25 kg/m(2)) adults., Main Outcome Measures: Participants were asked if they had ever received HP advice to lose weight and reported their desire to weigh less (ideal weight ≤95% of current weight) and whether they were attempting to lose weight., Results: Only 17% of overweight and 42% of obese respondents recalled ever having received HP advice to lose weight. HP advice was associated with wanting to weigh less (89% vs 61% among those not receiving advice) and attempting to lose weight (68% vs 37%). In multivariable analyses, HP advice to lose weight was associated with increased odds of wanting to weigh less (OR=3.71, 95% CI 2.10 to 6.55) and attempting to lose weight (OR=3.53, 95% CI 2.44 to 5.10) independent of demographic characteristics and weight status., Conclusions: HP advice to lose weight appears to increase motivation to lose weight and weight loss behaviour, but only a minority of overweight or obese adults receive such advice. Better training for HPs in delivering brief weight counselling could offer an opportunity to improve obese patients' motivation to lose weight.

Purpose of Review: The incidence of obesity and its associated comorbidities have significantly increased over the years with adverse health and financial consequences for society. Lifestyle changes are essential for the prevention and treatment of obesity but their benefit appears limited as inadequate and nonsustained weight loss results have been reported. Pharmacotherapy is frequently advocated as part of a weight loss strategy. In this review, we will discuss the antiobesity drugs with Food and Drug Administration approval and their cardiovascular implications., Recent Findings: Orlistat (Xenical) remains the single monotherapy that has approval in Europe. Topiramate (Topamax) and phentermine have long been approved in the United States, whereas lorcaserin and the extended release combination of phentermine with topiramate have recently gained approval. The development of single peptides targeting gut hormones or other host signals related to obesity may represent promising therapeutic options., Summary: Despite the recent failures of a number of antiobesity drugs, the pharmacotherapy of obesity is progressing rapidly. Treating the obese cardiovascular patient has proven challenging. Efficacy, safety and the sustainability of weight loss are key areas of focus in drug development strategies.

Objectives: This study sought to assess the associations of childhood adiposity with vascular phenotype in pre-pubertal children., Background: The early-life metabolic consequences have consistently been demonstrated in obese children, but the time course and development of any vascular changes remain largely unexplored., Methods: A total of 6,576 children age 10 to 11 years from the ALSPAC (Avon Longitudinal Study of Parents and Children) were studied. Childhood overweight and obesity were based on body mass index contemporary to vascular measures and supported by other adiposity measures, including fat mass and waist circumference on dual-energy x-ray absorptiometry. Heart rate, blood pressure, flow-mediated dilation in the brachial artery, and carotid to radial pulse wave velocity were measured in all children., Results: Overweight and obese children had higher heart rates (mean 72.4 ± 11 beats/min and 74.6 ± 12.2 beats/min vs. 71.7 ± 11 beats/min) and systolic blood pressures (mean 106.3 ± 9.1 mm Hg and 108 ± 10.2 mm Hg vs. 103.6 ± 9 mm Hg) compared with normal-weight peers. However, obese children had greater brachial diameters and resting and hyperemic blood flow, marginally increased endothelial function (higher flow-mediated dilation: mean 8.2 ± 3.2% vs. 8.1 ± 3.3%), and lower arterial stiffness (pulse wave velocity: mean 6.99 ± 1.0 m/s vs. 7.05 ± 1.23 m/s) compared with normal-weight children. These findings were not explained by metabolic differences., Conclusions: Greater childhood adiposity is associated with adverse cardiometabolic risk factors, but with no evidence of vascular damage at age 9 to 11 years. This could represent physiological adaptation to the hyperemic state of adiposity in childhood., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Raised blood pressure (BP) is the world's leading mortality risk factor. Childhood BP substantially predicts adult levels, and although both prenatal and postnatal growth influence it, their relative importance is debated. In a longitudinal study (Avon Longitudinal Study of Parents and Children) of 12 962 healthy children, we aimed to assess the relative contribution of different growth periods and of standardized measures of height versus weight-for-height (an adiposity marker) to BP at age 10 years. Conditional growth modeling was used in the 3230 boys and 3346 girls with BP measurements. Systolic BP was inversely associated with birth weight and weight-for-height but not length (-0.33, -0.27, and -0.12 mm Hg · SD(-1); P=0.003, 0.035, and 0.35, respectively). In infancy, weight, weight-for-height, and height gains were all positively associated with systolic BP (0.90, 0.41, and 0.82 mm Hg · SD(-1), respectively; all P<0.001). After infancy, all of the growth modalities were positively associated with systolic BP (weight, 1.91; weight-for-height, 1.56; height, 1.20 mm Hg · SD(-1); all P<0.001). Similar but weaker associations were found with diastolic BP. Although BP at 10 years was associated with both prenatal and early postnatal growth, their influence was small compared with that of later growth. Because BP ranking relative to the population is substantially determined in the first decade of life, a focus on strategies to reduce the development of adiposity from infancy onward, rather than an emphasis on the nutrition and weight of mothers and infants, should bring greater reductions in population BP.

Both obesity and acute high-intensity exercise increase oxidant stress levels. This study investigates whether selenium (Se) supplementation could be a potential effective therapy to reduce obesity-associated oxidant stress and exercise-induced oxidant stress. Ten normal-weight (NW) (22.80 ± 0.41 kg/m(2)) and ten overweight (OW) healthy subjects (28.00 ± 0.81 kg/m(2)) were assessed during a randomized double-blind Se supplementation study (200 µg sodium selenite/day for 3 weeks) with a 3-week placebo control and inversion of treatment periods. Blood levels of lipid hydroperoxide (LH), superoxide dismutase (SOD), erythrocyte glutathione (GSH), and total antioxidant status (TAS), were measured at rest, pre-, and postexercise (30 min 70% VO(2) max before and after treatment (pretreatment (week 0 and 12) and post-treatment (week 3 or 15)). At rest, compared to placebo, Se supplementation had no significant effect on LH, SOD, GSH, and TAS levels. However, Se supplementation decreased LH levels in the OW group, immediately postexercise (-0.25 ± 0.12 µmol/l, P = 0.05) compared to placebo treatment. Postexercise, with or without Se supplementation, no changes in TAS, SOD, and GSH levels were observed in both the NW and OW group. This study has highlighted a potential benefit of Se in reducing LH levels postexercise in OW individuals. Given that oxidant stress is a predictor of coronary events, it is imperative to better understand oxidant stress-related responses to lifestyle factors (in particular "high-risk" population groups) and potential antioxidant therapy.

Obesity is a significant health problem worldwide and is associated with a number of co-morbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease. A number of different pathophysiologic mechanisms including increased inflammation, oxidative stress, and insulin resistance have been associated with initiation and progression of atherosclerotic disease in obese individuals. Lifestyle modifications have provided modest results in weight reduction and the focus of interest has now shifted towards drug development to treat severely obese individuals with a body mass index (BMI) >30 kg/m(2) or those with a BMI >27 kg/m(2) who have additional co-morbidities. Different regimens focusing on dietary absorption or acting centrally to control hunger and food intake have been developed. However, their weight loss effect is, in most cases, modest and this effect is lost once the medication is discontinued. In addition, long-term use of these drugs is limited by significant side effects and lack of long-term safety and efficacy data. Orlistat is the only US FDA-approved medication for long-term use. A number of new medications are currently under investigation in phase III trials with promising preliminary results. This review comments on available anti-obesity pharmacologic regimens, their weight-loss benefit, and their impact on cardiovascular risk factors.

Aims: to examine the associations of several markers of adiposity and a wide range of cardiovascular risk factors and biomarkers in pre-pubertal children., Methods and Results: four measures of adiposity,body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry (DXA)-determined fat mass, and leptin concentration, were available in up to 7589 children aged 8.8-11.7 (9.9 mean) years from the Avon Longitudinal Study of Parents and Children (ALSPAC). Thirteen per cent of boys and 18.8% of girls were overweight, and 5.3% of boys and 5% of girls were obese. Body mass index was highly correlated with waist circumference (r = 0.91), DXA fat mass (r = 0.87), and leptin concentration (r = 0.75), and all had similar associations with cardiovascular risk factors. A 1 kg/m(2) greater BMI was associated with 1.4 mmHg (95% CI 1.25-1.44) higher systolic blood pressure (BP). In 5002 children, a 1 kg/m(2) greater BMI was associated with a 0.05 mmol/L (95% CI 0.036-0.055) higher non-high-density lipoprotein (HDL) cholesterol and 0.03 mmol/L (95% CI -0.034 to -0.025) lower HDL cholesterol. There were also graded associations with apolipoproteins A1 and B, interleukin-6, and C-reactive protein. Comparing children who were obese with those who were normal weight, the odds ratio for hypertension was 10.7 (95% CI 7.2-15.9) for boys and 13.5 (95% CI 9.4-19.5) for girls., Conclusion: in pre-pubertal UK children, overweight/obesity is common and has broadly similar associations with BP, HDL cholesterol, and non-HDL cholesterol to those observed in adults. Future research should evaluate whether effective interventions to maintain healthy weight in childhood could have important benefits for adult cardiovascular risk.

Objective: To estimate the incremental effect of waist circumference (WC) on health-care costs among overweight and obese subjects after adjusting for body mass index (BMI)., Methods: A prospective study. The subjects were members of Internet panels in the United States (US) and Germany. 10,816 individuals (United States: n = 5410; Germany: n = 5406) aged 30-70 years with BMI scores between 20 and 35 kg/m(2) were recruited and grouped by category: healthy weight (BMI 20-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI 30-35 kg/m(2)). Within the overweight and obese categories, the individuals were stratified by sex and within those subgroups, characterized as above or below the median WC. The subjects self-reported weight, WC, and health-care resource use at baseline, 3 months, and 6 months using online questionnaires. Over 65% of the recruited subjects completed all surveys. Resource utilization was translated into health-care costs by multiplying unit costs from national sources in each country. Annualized health costs were summarized for subjects with low and high WC within the overweight and obese categories. A two-part model generated predicted annual costs because of the WC difference controlling for BMI, demographic, and lifestyle variables among the overweight and obese subjects., Results: When BMI and other characteristics are constant, annual health-care costs are 16% to 18% higher in Germany and 20% to 30% higher in the United States for the subjects with a high WC compared with subjects with a low WC., Conclusions: Targeting people with a high waist circumference for weight management whether they are overweight or obese may maximize cost-efficacy.

This study was undertaken to investigate the association among BMI and lipid hydroperoxide (LH), total antioxidant status (TAS), superoxide dismutase (SOD), and reduced glutathione (GSH). Ninety (n = 90) healthy males and females (n = 23/67) (29 normal weight (BMI: 22.74 +/- 0.25 kg/m(2)), 36 overweight (BMI: 27.18 +/- 0.23 kg/m(2)), and 25 obese (33.78 +/- 0.48 kg/m(2))) participated in the study. Data collected included anthropometric measures, fasting blood glucose, lipid profile, LH, TAS, and enzymatic antioxidants (SOD, and reduced GSH). The results of the study showed that obese individuals had significantly increased LH levels compared to normal-weight individuals (obese vs. normal weight (0.88 +/- 0.05 vs. 0.67 +/- 0.03 micromol/l, P < 0.01)) but the increased levels were not significantly different when compared to the overweight group (obese vs. overweight (0.88 +/- 0.05 vs. 0.79 +/- 0.05 micromol/l)). No other consistent significant differences in TAS, SOD, and GSH were identified between groups. This study concluded that only obesity and not moderate overweight elevates LH levels. Furthermore, the levels of TAS, SOD, and GSH in obesity do not explain the increased LH levels observed in obesity.

Huntington's disease (HD) is a debilitating autosomal dominant, neurodegenerative disease with a fatal prognosis. Classical symptoms include motor disturbances, subcortical dementia and psychiatric symptoms but are not restricted to this triad. Patients often experience other problems such as weight loss, although why and when this occurs in the disease course is not known. We studied metabolism using whole body indirect calorimetry in both early stage HD patients and in the R6/2 transgenic mouse model of HD, at times before and after they displayed signs of disease. Using this combined approach we found that patients with early HD tended to be in negative energy balance for reasons not related to their movement disorder, which was paralleled in the transgenic R6/2 mice. These mice had significantly elevated total energy expenditure as they developed overt disease with weight loss due primarily to a loss of muscle bulk. This study has shown for the first time that in HD there is the development of early negative energy balance, which in turn may cause weight loss with loss of muscle bulk in particular. The reason for this is not known but may reflect a catabolic state secondary to hypothalamic pathology, as abnormalities have been reported in the hypothalamus early in the disease course.

In 2005, for the first time in European history, an extraordinary expert panel named BSCG (Bariatric Scientific Collaborative Group), was appointed through joint effort of the major European scientific societies which are active in the field of obesity management. Societies that constituted this panel were: IFSO - International Federation for the Surgery of Obesity, IFSO-EC - International Federation for the Surgery of Obesity - European Chapter, EASO - European Association for Study of Obesity, ECOG - European Childhood Obesity Group, together with the IOTF (International Obesity Task Force) which was represented during the completion process by its representative. The BSCG was composed not only of the top officers representing the respective scientific societies (four acting presidents, two past presidents, one honorary president, two executive directors), but was balanced with the presence of many other key opinion leaders in the field of obesity. The BSCG composition allowed the coverage of key disciplines in comprehensive obesity management, as well as reflecting European geographical and ethnic diversity. This joint BSCG expert panel convened several meetings which were entirely focused on guidelines creation, during the past 2 years. There was a specific effort to develop clinical guidelines, which will reflect current knowledge, expertise and evidence based data on morbid obesity treatment., (Copyright 2008 S. Karger AG, Basel.)

Objective: To investigate the impact of 30-minute walking exercise at 70% VO2max on tissue plasminogen activator (t-PA) Ag and plasminogen activator inhibitor type 1 (PAI-1) Ag in obese sedentary males., Research Methods and Procedures: A controlled observational study of the effect of a 30-minute acute exercise bout at 70% VO2max on plasma t-PA antigen and PAI-1 antigen in 10 obese sedentary males matched for age, ethnic origin, and smoking status with 10 nonobese sedentary male controls., Results: The obese group remained hypofibrinolytic compared with the nonobese group at all time-points before, during, and after exercise. t-PA increased in both groups with exercise before returning to baseline values 30 minutes after exercise. PAI-1 did not significantly change in either group with exercise but rose significantly 30 minutes after exercise in the obese group., Discussion: The reduction in fibrinolytic potential in the obese group represents an increase in acute thrombotic risk and could account for the increased incidence of exercise-associated myocardial infarction observed in sedentary obese groups.

Purpose: The role of thyroxine replacement in subclinical hypothyroidism remains unclear. We performed a 6-month randomized, double-blind, placebo-controlled trial to evaluate the effects of thyroxine treatment for mild subclinical hypothyroidism, defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level (0.8-16 ng/dL)., Subjects and Methods: We randomly assigned 40 women with mild subclinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment (n = 23; 50 to 100 microg daily) or placebo (n = 17). Health-related quality of life (Hospital Anxiety and Depression scale, 30-item General Health Questionnaire), fasting lipid profiles, body weight, and resting energy expenditure were measured at baseline and 6 months., Results: The most common presenting symptoms were fatigue (n = 33 [83%]) and weight gain (n = 32 [80%]). At presentation, 20 women (50%) had elevated anxiety scores and 22 (56%) had elevated scores on the General Health Questionnaire. Thirty-five women completed the study. There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic, lipid, or anthropometric variables measured, expressed as the mean change in the thyroxine group minus the mean change in the placebo group: body mass index, -0.3 kg/m(2) (95% confidence interval [CI]: -0.9 to 0.4 kg/m(2)); resting energy expenditure, -0.2 kcal/kg/24 h (95% CI: -1.3 to 1.0 kcal/kg/24 h); and low-density lipoprotein cholesterol, -4 mg/dL (95% CI: -23 to 15 mg/dL). There was a significant worsening in anxiety scores in the thyroxine group (scores increased in 8 of 20 women and were unchanged in 2 of 20) compared with the placebo group (scores increased in 1 of 14 women and were unchanged in 6 of 14; P = 0.03). CONCLUSIONS; We observed no clinically relevant benefits from 6 months of thyroxine treatment in women with mild subclinical hypothyroidism.