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Although estimates of the prevalence of cardiac arrhythmias in healthy volunteers exist, there is a lack of baseline data in other specific populations, such as people living with overweight and obesity, who are increasingly involved in clinical trials. This study investigated the baseline prevalence of arrhythmias in participants with overweight or obesity in 2 phase 1 trials of weight management medications (NCT03661879, NCT03308721). Participants aged 18-55 years, without a history of cardiovascular disease, and with body mass index (BMI) 25.0-39.9 kg/m

The growth in prevalence of obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) has become one of the most important global health challenges. The three connections are closely connected in their epidemiology and pathophysiology. Currently weight loss is the most effective treatment for NAFLD (even in the minority of patients who do not have obesity) and is at recommended in all national and international guidelines. Accumulating evidence has shown that weight loss, whether achieved by diet and lifestyle interventions, bariatric surgery or pharmacotherapy can improve biomarkers of NAFLD, as well as prevent progression, and in some cases reverse, fibrosis. There is a dose dependency of weight loss with NAFLD improvement. Pharmacotherapy with anti-obesity medications alone, or in combination with intensive lifestyle interventions or other weight loss drugs is closing the efficacy gap between diet and exercise and weight loss surgery. Give the importance of providing effective weight loss treatment to patients with NAFLD, weight management services need to be made increasingly available and embedded within hepatology services. This narrative review addresses the evidence for weight loss optimising liver outcomes in people with NAFLD. This article is protected by copyright. All rights reserved.

There is a growing unmet need for more effective treatment of obesity and its complications. While current anti-obesity medications are effective and offer real clinical benefits over diet and lifestyle interventions, they cannot meet the levels of efficacy and reduction of hard endpoint outcomes seen with bariatric surgery. As knowledge on the control of body weight unravels, the complexity of this physiology opens the opportunity to new druggable targets. Currently, gut peptide analogues such as semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, and the dual agonist GLP-1 and gastric inhibitory polypeptide (GIP) tirzepatide are the furthest advanced in clinical development and seem likely to meet current regulatory requirements within the next year or so. However, current regulatory requirements are out of step with the efficacy of new compounds and concepts relating to obesity and its complications. Many other drugs in early development will target different pathways of energy balance, raising the possibility of drug combinations to maximise efficacy as for other chronic disease such as hypertension and diabetes. This will allow more complex and personalised guidelines to evolve.

Objective Previous studies using longitudinal weight data to characterize obesity are based on populations of limited size and mostly include individuals of all body mass index (BMI) levels, without focusing on weight changes among people with obesity. This study aimed to identify BMI trajectories over 5 years in a large population with obesity, and to determine the trajectories' association with mortality. Methods For inclusion, individuals aged 30–74 years at index date (1 January 2013) with continuous membership in Clalit Health Services from 2008 to 2012 were required to have ≥1 BMI measurement per year in ≥3 calendar years during this period, of which at least one was ≥30 kg/m2. Latent class analysis was used to generate BMI trajectories over 5 years (2008–2012). Cox proportional hazards models were used to assess the association between BMI trajectories and all‐cause mortality during follow‐up (2013–2017). Results In total, 367,141 individuals met all inclusion criteria. Mean age was 57.2 years; 41% were men. The optimal model was a quadratic model with four classes of BMI clusters. Most individuals (90.0%) had stable high BMI over time. Individuals in this cluster had significantly lower mortality than individuals in the other trajectory clusters (p

As this issue of Clinical Obesity goes to press, the world is reeling from the health, economic and social impact of the global pandemic of COVID‐19 (the disease) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It is becoming clear that several factors put people living with obesity at greater risk of the disease.

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.

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.

Obesity during pregnancy is associated with increased risks of thromboembolism, gestational diabetes, pre‐eclampsia, miscarriage, congenital anomaly, macrosomia and stillbirth. The current practice, directed at reducing gestational weight gain, is largely ineffective. The present pilot study was designed to assess the acceptability of a 24‐week intensive weight management programme (IWMP; full meal replacement followed by partial meal replacement and weight stabilization) to achieve weight loss for women with obesity requesting removal of their intra‐uterine contraceptive device in order to conceive. Twenty six (65%) of eligible participants consented to the IWMP; three received this as routine National Health Service care in the University College Hospital clinic and 14 participated in the study. The commonest reasons for not participating were dislike of milk, anxiety and lack of support from family and friends. Omitting one woman who dropped out because of problems unrelated to the intervention, the completion rate was 46.2%. Including all women who started the programme, mean body mass index decreased significantly (P = 0.005) from 37.8 to 35.3 kg/m². The median percentage decrease was significantly (P = 0.007) greater for women who completed the study (14.2) compared to those who dropped out (1.2). These results suggest an impressive level of weight loss in about one third of all women offered the IWMP who had to defer what they were seeking (pregnancy) while following a challenging programme that they were not seeking. However, studies of other interventions, such as partial meal replacement or commercial products, which may have higher rates of completion are still required.

Aims The comparative efficacy of Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c, age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2‐year post‐surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. Methods A retrospective single‐centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. Results The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817–0.916); DiaRem: 0.865 (95%CI: 0.814–0.915), P=0.856]. Two‐year % weight loss was higher post RYGB [26.6 (95%CI: 24.8–28.4)] vs post‐sleeve gastrectomy [20.6 (95%CI: 18.3–22.8), P, What's new? Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy can lead to Type 2 diabetes remission in people with obesity and Type 2 diabetes. The impact of post‐surgery weight loss and surgical procedure type upon Type 2 diabetes remission rates are unclear.The DiaRem score predicts post‐RYGB Type 2 diabetes remission but does not include Type 2 diabetes duration, which negatively associates with Type 2 diabetes remission rates.We show that the novel DiaBetter Score, which includes Type 2 diabetes duration, predicts Type 2 diabetes remission at 2 years following RYBG and sleeve gastrectomy with comparable predictive power to DiaRem.Importantly, we show that percentage weight loss rather than procedure type determines Type 2 diabetes remission 2 years postoperatively.

The challenge of managing the epidemic of patients with severe and complex obesity disease in secondary care is largely unmet. In England, the National Institute of Health and Care Excellence and the National Health Service England have published guidance on the provision of specialist (non-surgical) weight management services. We have undertaken a systematic review of 'what evidence exists for what should happen in/commissioning of: primary or secondary care weight assessment and management clinics in patients needing specialist care for severe and complex obesity?' using an accredited methodology to produce a model for organization of multidisciplinary team clinics that could be developed in every healthcare system, as an update to a previous review. Additions to the previous guidance were multidisciplinary team pathways for children/adolescent patients and their transition to adult care, anaesthetic assessment and recommendations for ongoing shared care with general practitioners, as a chronic disease management pathway.

AIMS: Obesity is associated with increased risk for heart failure. We analysed data from the Swedish Obese Subjects (SOS) study, a prospective matched cohort study, to investigate whether bariatric surgery reduces this risk. METHODS AND RESULTS: From the total SOS population (n = 4047), we identified 4033 obese individuals with no history of heart failure at baseline, of whom 2003 underwent bariatric surgery (surgery group) and 2030 received usual care (control group). First-time principal diagnoses of heart failure were identified by crosschecking the SOS database with the Swedish National Patient Register and the Swedish Cause of Death Register using diagnosis codes. During a median follow-up of 22 years, first-time heart failure occurred in 188 of the participants treated with surgery and in 266 of those receiving usual care. The risk of developing heart failure was lower in the surgery group than in the control group [sub-hazard ratio 0.65, 95% confidence interval (CI) 0.54–0.79; P

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.

Background Overweight/obesity is associated with significant morbidity, mortality and costs. Weight loss has been shown to reverse some of these effects, reducing the risk of chronic diseases such as cardiovascular disease (CVD). We aimed to determine potential monies available, from an English National Health Service perspective, for weight loss interventions to be cost-effective in the prevention of CVD. Methods A Markov model was developed, populated with overweight/obese individuals from the Health Survey for England aged 30-74 years, free of pre-existing CVD, and with available risk factor information to calculate CVD risk. All individuals were free of CVD at baseline and with each annual cycle, could transition to other health states of primary CVD, secondary CVD or death according to transition probabilities for a maximum period of ten years, or until death. Utilities, costs and the effects of weight loss on CVD risk factors were applied. The potential monies available for CVD prevention strategies provided the incremental cost-effectiveness ratio met UK arbitrary limits of between £20 000 and £30 000 was determined. Results Applying the effects of weight loss on CVD risk factors prevented 12 CVD events and saved 12 quality-adjusted life years over 10 years per 1 000 individuals. £27-£39 was available per person per year for up to 10 years when meeting the UK arbitrary limits. Conclusions Individual annual financial allowances for weight loss interventions to be considered cost-effective is relatively low; however, as a large proportion of the population is affected, wide cheap societal interventions are important.

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta-analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta-analysis, with sub-group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (-2.68 mmHg, 95% CI -3.37, -2.11), diastolic blood pressure (-1.34 mmHg, 95% CI -1.71, -0.97), low-density lipoprotein cholesterol (-0.20 mmol L(-1) , 95% CI -0.29, -0.10), triglycerides (-0.13 mmol L(-1) , 95% CI -0.22, -0.03), fasting plasma glucose (-0.32 mmol L(-1) , 95% CI -0.43, -0.22) and haemoglobin A1c(-0.40%, 95% CI -0.52, -0.28) over 6-12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub-group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity.

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.

Despite the availability of a growing range of interventions to assist control of body weight for people with excess weight or obesity, only a small proportion of people achieve their weight loss goals and are able to maintain body weight reductions in the long term. Negative attitudes and beliefs are often found among physicians and others involved in treating obesity and may adversely impact the effectiveness of management. In this international study, healthcare professionals were invited to complete an online survey of their attitudes and practice in the management of excess body weight. A total of 335 clinicians completed the survey of whom approximately half were based in Europe. A key finding from the survey is that, while participants are generally confident in their ability to manage overweight and obesity effectively, they also report that most of their patients are not successful in achieving their weight loss goals. At the same time, participants tended to overestimate the effectiveness of current medical management in maintaining reductions in body weight. Educational initiatives addressing the real-life effectiveness of different weight control interventions may help to close the gap between clinicians' perceptions and reality in the management of excess body weight.

Background We report striking and unanticipated improvements in maladaptive behaviours in Prader–Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild–moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia. Methods Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post-implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly. Results Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food-seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours. Conclusions We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally.

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' 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.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 kgm−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.

BACKGROUND: Fasting during the month of Ramadan entails abstinence from eating and drinking between dawn and sunset and a major shift in meal times and patterns with associated changes in several hormones and circadian rhythms; whether there are accompanying changes in energy metabolism is unclear. OBJECTIVE: We have investigated the impact of Ramadan fasting on resting metabolic rate (RMR), activity, and total energy expenditure (TEE). DESIGN: Healthy nonobese volunteers (n = 29; 16 women) fasting during Ramadan were recruited. RMR was measured with the use of indirect calorimetry. In subgroups of participants, activity (n = 11; 5 women) and TEE (n = 10; 5 women) in free-living conditions were measured with the use of accelerometers and the doubly labeled water technique, respectively. Body composition was measured with the use of bioelectrical impedance. Measurements were repeated after a wash-out period of between 1 and 2 mo after Ramadan. Nonparametric tests were used for comparative statistics. RESULTS: Ramadan fasting did not result in any change in RMR (mean ± SD: 1365.7 ± 230.2 compared with 1362.9 ± 273.6 kcal/d for Ramadan and post-Ramadan respectively, P = 0.713, n = 29). However, controlling for the effects of age, sex, and body weight, RMR was higher in the first week of Ramadan than in subsequent weeks. During Ramadan, the total number of steps walked were significantly lower (n = 11, P = 0.001), while overall sleeping time was reduced and different sleeping patterns were seen. TEE did not differ significantly between Ramadan and post-Ramadan (mean ± SD: 2224.1 ± 433.7 compared with 2121.0 ± 718.5 kcal/d for Ramadan and post-Ramadan, P = 0.7695, n = 10). CONCLUSIONS: Ramadan fasting is associated with reduced activity and sleeping time, but no significant change in RMR or TEE. Reported weight changes with Ramadan in other studies are more likely to be due to differences in food intake. This trial is registered at clinicaltrials.gov as NCT02696421.

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/m2 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

BackgroundMendelian randomization (MR) studies of body mass index (BMI) and cardiovascular health in mid-to-late life suggest causal relationships, but the nature of these has not been explored systematically at younger ages. Using complementary MR and recall-by-genotype (RbG) methodologies, our objective was to estimate the causal effect of BMI on detailed measures of cardiovascular health in a population of young healthy adults.Methods and FindingsData from the Avon Longitudinal Study of Parents and Children were used. For MR analyses, a genetic risk score (GRS) comprising 97 independent single nucleotide polymorphisms (SNPs) and constructed using external weighting was used as an instrument to test the causal effect of each unit increase in BMI (kg/m2) on selected cardiovascular phenotypes measured at age 17 (N=7909). An independent enriched sample from the same cohort participated in a RbG study at age 21, which enabled more detailed cardiovascular phenotyping (N=418; 191/227 from the lower/upper ∼30% of a genome-wide GRS distribution predicting variation in BMI). The causal effect of BMI on the additional cardiovascular phenotypes was assessed by comparing the two recalled groups. Difference in mean BMI between RbG groups was 3.85kg/m2(95% CI: 2.53, 4.63;P=6.09×1011). In both MR and RbG analyses, results indicated that higher BMI causes higher blood pressure (BP) and left ventricular mass (indexed to height2.7, LVMI) in young adults (e.g. difference in LVMI per kg/m2using MR: 1.07g/m2.7; 95% CI: 0.62, 1.52; P=3.87×10−06and per 3.58kg/m2using RbG: 1.65g/m2.795% CI: 0.83, 2.47; P=0.0001). Additionally, RbG results indicated a causal role of higher BMI on higher stroke volume (SV; difference per 3.58kg/m2: 1.49ml/m2.04; 95% CI: 0.62, 2.35;P=0.001) and cardiac output (CO; difference per 3.58kg/m2: 0.11l /min/m1.83; 95% CI: 0.03, 0.19;P=0.01). Neither analysis supported a causal role of higher BMI on heart rate.ConclusionsComplementary MR and RbG causal methodologies, together with a range of appropriate sensitivity analyses, showed that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. These consistent results support efforts to prevent or reverse obesity in the young.

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/m2 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.

Background and aims An inverse relationship between (serum) total bilirubin and risk of cardiovascular disease has been reported previously, but longitudinal data on overweight and obese patients are lacking. We have investigated the relationship between total bilirubin and cardiovascular adverse events in a large group of patients with risk factors for cardiovascular disease who were enrolled in a large weight loss trial. Methods and results Data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, including almost 10.000 overweight/obese high cardiovascular risk patients, were used. The relationship between total bilirubin level at screening and the primary outcome (i.e. non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death) for the entire study period was investigated using Cox proportional hazards models. The population was divided into four groups based on total bilirubin levels (normal range 5–25 μmol/L). Time-dependent Cox analyses were also performed to adjust for weight loss over time. Initial analyses adjusted for sex, age and treatment allocation showed significantly reduced hazard ratios of 0.80 (95% confidence interval 0.68–0.94), 0.73 (0.62–0.86) and 0.77 (0.65–0.91), for the three higher total bilirubin groups: >8 and ≤10 μmol/L, >10 and ≤13 μmol/L and >13 μmol/L (5–95 interpercentile range for total bilirubin at screening; 6–19 μmol/L), compared to the lowest total bilirubin group ≤8 μmol/L. When adjusting for classical cardiovascular risk factors, estimates increased towards unity. Additional adjustment for indicators of liver function did not alter the results. A time-dependent Cox model, adjusted for weight loss, demonstrated a similar trend. Conclusion Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.

This commentary refers to ‘Early vascular damage from smoking and alcohol in teenage years: the ALSPAC study’, by M. Charakida et al., 345–353.

The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events. A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27–45 kg m–2 were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions. During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (−8.1±10.5 mm Hg with

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.

AIMS: Obesity is associated with an increased incidence of mortality. The Sibutramine Cardiovascular Outcomes (SCOUT) trial can provide the first evidence of the effect of intentional weight loss on mortality in an obese population at high risk.METHODS: SCOUT was a randomized, double-blind, placebo-controlled trial testing sibutramine vs. placebo. Eligibility for the trial required both men and women aged at least 55 years, with BMI of at least 27 kg/m and 45 kg/m or less. Study participants with type 2 diabetes mellitus (T2DM) only should have at least one other risk factor defined as hypertension, dyslipidaemia, smoking, or diabetic nephropathy, and/or they had a history of cardiovascular disease. Study participants were stratified in three groups: patients with T2DM, patients with a prior cardiovascular event but without diabetes, and patients with both T2DM and a prior cardiovascular event.The relationship between weight loss and mortality (all-cause, cardiovascular, and noncardiovascular) was investigated with Cox regression models.RESULTS: The main study showed that all-cause mortality was not different in patients allocated to sibutramine or placebo. This ancillary analysis demonstrates that there is a general trend showing higher mortality in patients with the greatest weight loss (weight reduction >10 kg) and in those with increasing weight (>1 kg). If integrated weight loss (area under the curve from baseline to 12 months) is used, these observations are confirmed. The impact of substantial weight loss on mortality is marked in those dying of noncardiovascular causes, specifically cancer.CONCLUSION: The relationship between weight change and mortality differs for cardiovascular and noncardiovascular mortality.

Background There is no established primary care solution for the rapidly increasing numbers of severely obese people with body mass index (BMI) > 40 kg/m2. Aim This programme aimed to generate weight losses of ≥15 kg at 12 months, within routine primary care. Design and setting Feasibility study in primary care. Method Patients with a BMI ≥40 kg/m2 commenced a micronutrient-replete 810–833 kcal/day low-energy liquid diet (LELD), delivered in primary care, for a planned 12 weeks or 20 kg weight loss (whichever was the sooner), with structured food reintroduction and then weight-loss maintenance, with optional orlistat to 12 months. Result Of 91 patients (74 females) entering the programme (baseline: weight 131 kg, BMI 48 kg/m2, age 46 years), 58/91(64%) completed the LELD stage, with a mean duration of 14.4 weeks (standard deviation [SD] = 6.0 weeks), and a mean weight loss of 16.9 kg (SD = 6.0 kg). Four patients commenced weight-loss maintenance omitting the food-reintroduction stage. Of the remaining 54, 37(68%) started and completed food reintroduction over a mean duration of 9.3 weeks (SD = 5.7 weeks), with a further mean weight loss of 2.1 kg (SD = 3.7 kg), before starting a long-term low-fat-diet weight-loss maintenance plan. A total of 44/91 (48%) received orlistat at some stage. At 12 months, weight was recorded for 68/91 (75%) patients, with a mean loss of 12.4 kg (SD = 11.4 kg). Of these, 30 (33% of all 91 patients starting the programme) had a documented maintained weight loss of ≥15 kg at 12 months, six (7%) had a 10–15 kg loss, and 11 (12%) had a 5–10 kg loss. The indicative cost of providing this entire programme for wider implementation would be £861 per patient entered, or £2611 per documented 15 kg loss achieved. Conclusion A care package within routine primary care for severe obesity, including LELD, food reintroduction, and weight-loss maintenance, was well accepted and achieved a 12-month-maintained weight loss of ≥15 kg for one-third of all patients entering the programme.

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.

BACKGROUND: Current guidelines for obesity management emphasize the improvements in health risks associated with weight losses of 5-10% initial weight. However, most of the data is derived from periods of acute weight loss and may not represent the true effect in the longer term or in obese but otherwise healthy individuals. This study examines the temporal changes in risk factors for cardiovascular disease with weight change over 52 weeks. METHODS: In total, 57 overweight women (age 43.7 +/- 9.1 years, mean BMI of 31.7 kg/m2, range 27.2-38.5 kg/m2) with no other significant medical history, entered a milk-based, low-energy weight loss programme for 12 weeks and were then monitored without further intervention until 52 weeks. Weight, fat mass, fasting plasma insulin, lipids and blood pressure were measured at 0, 12, 24 and 52 weeks. RESULTS: The mean weight change in sequential periods was -11.6% (p < 0.0001), +1.1% (p = 0.02) and +5.2% (p < 0.0001). The change from baseline to 1 year being -6.0% (p < 0.0001) an 11% (p < 0.0001) reduction in initial body fat mass. Initial weight loss (0-12 weeks) was positively correlated with greater longer term weight loss (0-52 weeks, r = 0.75, p < 0.0001) and not with weight regain (12-52 weeks, r = 0.14, p = 0.28). Despite significant improvements in insulin sensitivity, lipid profile and blood pressure (BP) with acute weight loss, in the group overall, only benefits in BP were maintained after 52 weeks. However, improvements in insulin sensitivity were sustained in those who maintained more than 5% weight loss, and those with higher baseline metabolic risk had greater benefits with weight loss. Change in waist circumference was better than BMI or fat mass in predicting improvements in metabolic risk in these obese women. CONCLUSIONS: This study suggests, in otherwise apparently healthy obese women, the rationale of targeting individuals most likely to benefit from weight management. Most importantly it highlights the need to focus on achieving initial weight losses of greater than 10% to maintain longer term losses of at least 5% and the associated health benefits.

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.

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.

Background: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial but has variable adherence and response. Method: We demonstrate the role of GLP1, counter-regulatory hormones and the subsequent response of GLP1 to somatostatin analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years after GBS. Plasma GLP1, insulin and glucose were measured for 5 h on three settings: i) a 75 g oral glucose tolerance test (OGTT); ii) a standard liquid test meal (LTM); and iii) an OGTT 30 min after a s.c. injection of 100 mg octreotide. Results: In comparison with obese non-diabetic controls, the patient had an elevated fasting and a markedly enhanced GLP1 response during the OGTT, followed by an exaggerated insulin response and a subsequent low glucose level. The GLP1 response to a LTM was similar but greater. Octreotide given prior to the OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia. Octreotide therapy significantly improved the patient’s neuroglycopaenic symptoms. The hormone profile was reassessed after 6 months following the LTM preceded by octreotide injection. Peak GLP1 and insulin responses were less pronounced than pretreatment responses and without hypoglycaemia. The patient was treated with lanreotide and had remained symptom-free and euglycaemic for 4 years. Conclusion: An exaggerated incretin response following altered gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS patient. Somatostatin successfully suppressed this response acutely and in the long term, thereby avoiding pancreatectomy and its sequelae.

Three double-blind, placebo-controlled, three-parallel-group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP-945,598 for weight loss and weight-loss maintenance. Two trials were designed to be 2 years in duration (in obese and overweight patients) and one as a 1-year study (in obese and overweight patients with type 2 diabetes). However, the 2-year trials and the CP-945,598 development program were terminated before completion due to changing regulatory perspectives of CB1 receptor-related drugs. In total, 1,253 and 2,536 participants in the two 2-year multinational and North American studies were randomized to 10-mg CP-945,598 (n = 360; 718); 20-mg CP-945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10-mg CP-945,598 (n = 318); 20-mg CP-945,598 (n = 320); and placebo (n = 337) in the 1-year multinational diabetes trial. Baseline demographics were similar between treatment groups within each trial. One year of treatment with CP-945,598 resulted in a dose-related mean percentage reduction from baseline body-weight in all trials. A significant proportion of all participants also achieved 5% and 10% weight loss after 1 year. In participants with mainly well-controlled type 2 diabetes, the combination of lifestyle and CP-945,598 induced substantial improvements in glycemic control. The most frequent adverse events (AEs) for CP-945,598 were: diarrhea, nausea, nasopharyngitis, and headache. Self-reported experiences of anxiety and suicidal thoughts were higher with CP-945,598 than placebo, as were the incidence of depression and depressed mood. However, the reported increases in psychiatric symptoms were not consistently dose dependent.

Obesity is recognised as a global epidemic and the most prevalent metabolic disease world-wide. Specialised obesity services, however, are not widely available in Europe, and obesity care can vary enormously across European regions. The European Association for the Study of Obesity (EASO, www.easo.org) has developed these criteria to form a pan-European network of accredited EASO-Collaborating Centres for Obesity Management (EASO-COMs) in accordance with accepted European and academic guidelines. This network will include university, public and private clinics and will ensure that the obese and overweight patient is managed by a holistic team of specialists and receives comprehensive state-ofthe-art clinical care. Furthermore, the participating centres, under the umbrella of EASO, will work closely for quality control, data collection, and analysis as well as for education and research for the advancement of obesity care and obesity science.

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/m2 greater BMI was associated with 1.4mmHg (95% CI 1.25–1.44) higher systolic blood pressure (BP). In 5002 children, a 1 kg/m2 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.

Background: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. Methods: Using the 2006 NICE obesity health economic model, a primary care weight management programme ( Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions ( type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background ( untreated) weight gain. Results: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was 59.83 pound per patient entered. Even assuming dropouts/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was 2017 pound where background weight gain was limited to 0.5 kg/year, and 2651 pound at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory ( very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. Conclusion: Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.