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Background: Reducing weight stigma in healthcare is critical to supporting and improving the health of people living with overweight or obesity and decreasing the risk of adverse patient outcomes. We were invited as stigma researchers to participate in an online workshop alongside community members, healthcare professionals and policymakers to codesign guidance for reducing weight stigma in healthcare. This workshop prompted us to reflect on why and how weight stigma should be addressed in healthcare, and to provide recommendations for healthcare professionals and policymakers to reduce weight stigma in healthcare., Objective: This paper presents our reflections and recommendations for addressing weight stigma in healthcare following the codesign workshop., Discussion: Recommendations include targeting individual healthcare professionals and involving clear, practical guidelines and training that leverage the notions of 'do no harm', improving practice and recognising biases. Importantly, such strategies must be couched in broader structural approaches to weight stigma reduction.

Purpose: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care., Materials and Methods: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review., Results: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma., Conclusion: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making., (© 2024. The Author(s).)

Background: Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care., Methods: We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472., Findings: Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p<0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p<0·0001) or without (0·704, 0·588-0·843, p<0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup I 2 95·7%, p<0·0001). Median life expectancy was 9·3 years (95% CI 7·1-11·8) longer for patients with diabetes in the surgery group than the non-surgical group, whereas the life expectancy gain was 5·1 years (2·0-9·3) for patients without diabetes. The numbers needed to treat to prevent one additional death over a 10-year time frame were 8·4 (95% CI 7·8-9·1) for adults with diabetes and 29·8 (21·2-56·8) for those without diabetes. Treatment effects did not appear to differ between gastric bypass, banding, and sleeve gastrectomy (I 2 3·4%, p=0·36). By leveraging the results of this meta-analysis and other published data, we estimated that every 1·0% increase in metabolic-bariatric surgery utilisation rates among the global pool of metabolic-bariatric candidates with and without diabetes could yield 5·1 million and 6·6 million potential life-years, respectively., Interpretation: Among adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without., Funding: None., Competing Interests: Declaration of interests JBD has consultancies with Bariatric Advantage, iNova, and Reshape; and is on advisory boards for Novo Nordisk and Nestlé Health Science. LMK has received funds from Boehringer Ingelheim, Ethicon, Gelesis, GI Dynamics, Johnson & Johnson, Pfizer, Novo Nordisk, and Rhythm Pharmaceuticals. DEC is on the scientific advisory boards for GI Dynamics, DyaMx, Magnamosis, Metavention, and Gila Therapeutics. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Following metabolic and bariatric surgery (MBS), most adolescents experience weight loss and improvement of many obesity-associated complications (OACs). The relationship between weight loss and remission of OACs after MBS in adolescents has not been well described., Methods: The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) is a multi-institutional prospective observational study of adolescents who underwent MBS between 2007 and 2012. Lower-weight-loss responders (LWLRs) were defined as having <20% total body weight loss (TBWL) and higher-weight-loss responders (HWLRs) were defined as having ≥20% TBWL at 5 years after MBS. The prevalence of OACs was compared at baseline and 5 years after MBS., Results: Both LWLRs (n = 114) and HWLRs (n = 78) lost significant weight within the first year following MBS; however, the TBWL at 5 years for the LWLRs was 8.6% ± 9.5% compared with 33.8% ± 9.2% for the HWLRs. Those in the HWLR group were more likely to experience durable remission of composite dyslipidemia at 5 years, whereas there were no differences between groups in remission rates of all other OACs., Conclusions: Greater weight loss after MBS in adolescents was associated with greater remission of composite dyslipidemia; however, remission of other OACs was not dependent on major sustained weight loss., (© 2020 The Obesity Society.)

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

People with obesity commonly face a pervasive, resilient form of social stigma. They are often subject to discrimination in the workplace as well as in educational and healthcare settings. Research indicates that weight stigma can cause physical and psychological harm, and that affected individuals are less likely to receive adequate care. For these reasons, weight stigma damages health, undermines human and social rights, and is unacceptable in modern societies. To inform healthcare professionals, policymakers, and the public about this issue, a multidisciplinary group of international experts, including representatives of scientific organizations, reviewed available evidence on the causes and harms of weight stigma and, using a modified Delphi process, developed a joint consensus statement with recommendations to eliminate weight bias. Academic institutions, professional organizations, media, public-health authorities, and governments should encourage education about weight stigma to facilitate a new public narrative about obesity, coherent with modern scientific knowledge.

Background: In Asia, metabolic-bariatric surgery (MBS) rates have grown rapidly in parallel with rising prevalence of obesity and type 2 diabetes (T2D)., Objective: The objective of this study was to identify factors that influence glycemic outcomes and diabetes remission 12 months after sleeve gastrectomy (SG) or gastric bypass (GB) in a multiethnic Asian cohort., Setting: The study's setting was in a tertiary hospital in Singapore., Methods: Data from 145 T2D patients who had SG (37%) or GB (63%) and at least 1-year follow-up were analyzed. Diabetes remission was defined as hemoglobin A1c ≤ 6.0% without diabetes medications. Analysis involved binary logistic regression to identify predictors and general linear regression for variables associated with glycemic improvement after surgery., Results: Baseline parameters are as follows: BMI 40.0 ± 7.6 kg/m 2 , A1c 8.4 ± 1.6%, diabetes duration 9.3 years, ethnic composition: Chinese (51.7%), Malay (23.4%), Indian (20.7%), Others (4.1%). 55.9% achieved diabetes remission at 1 year. Baseline A1c, baseline BMI, and diabetes duration were significant pre-operative factors for remission (cumulative R 2  = 0.334). At 12 months, percentage weight loss was similar after SG (24.1 ± 7.4%) and GB (25.4 ± 7.4%, p = 0.31). Greater A1c decrease was seen with GB compared to SG (2.7 ± 1.6 vs 2.0 ± 1.5%, p = 0.006), significant even after adjustment for weight loss, age, BMI, baseline A1c, and diabetes duration (p = 0.033). Weight loss at 12 months also correlated independently with A1c reduction. Ethnicity did not influence weight loss, diabetes remission, or glycemic control after MBS., Conclusion: Baseline A1c, baseline BMI, and diabetes duration independently predict diabetes remission after MBS. GB is more effective in controlling T2D compared to SG despite similar weight loss, whereas ethnicity does not play a significant role in the multiethnic Asian cohort.

Purpose of Review: This review examines the food addiction model and the role of food hedonic pathways in the pathogenesis and treatment of obesity., Recent Findings: The hedonic pathway interacts with the obesogenic environment to override homeostatic mechanisms to cause increase in body weight. Weight gain sustained over time leads to "upward setting" of defended level of body-fat mass. There are neurobiological and phenotypic similarities and differences between hedonic pathways triggered by food compared with other addictive substances, and the entity of food addiction remains controversial. Treatment for obesity including pharmacotherapy and bariatric surgery impacts on neural pathways governing appetite and hedonic control of food intake. The food addiction model may also have significant impact on public health policy, regulation of certain foods, and weight stigma and bias. Recent rapid progress in delineation of food hedonic pathways advances our understanding of obesity and facilitates development of effective treatment measures against the disease.

Objective: Obesity is associated with a decline in health-related quality of life (HRQOL), while weight loss and exercise training have a positive influence. The aim of this systematic review was to compare the effects of energy restriction (ER) alone intervention to diet and exercise intervention on HRQOL., Methods: MEDLINE, CINAHL and PsycINFO databases were searched for randomised controlled trials examining HRQOL through lifestyle interventions which examined ER and energy restriction plus exercise in obese adults., Results: Nine hundred and fifty-two papers were assessed for inclusion in this review with nine being deemed suitable. This review indicates that four studies provide evidence to support the role of exercise in addition to ER to improve HRQOL in adults with obesity. The findings of this review are limited due to the limited number of studies as well as substantial heterogeneity in ER, exercise prescription variables and outcome measures utilised within studies., Conclusions: A definitive conclusion regarding the capacity of exercise to facilitate greater improvement in HRQOL than diet alone, or, to formulate an exercise prescription for obese adults to address HRQOL is not feasible based on the existing evidence. Future studies should utilise comparable HRQOL assessment tools along with ensuring full reporting of results.

Aims: Elevated serum uric acid (SUA) is often present in conditions associated with increased cardiovascular risk yet it is not recognized as a marker of risk. We evaluated whether SUA was associated with evidence of early markers of cardiovascular risk factor including subclinical early organ damage, sympathetic tone and metabolic profile in a healthy population with a high prevalence of obesity., Material and Methods: Data from 281 patients (175 women and 106 men, mean age: 35.5 ± 0.8 years, mean BMI: 33.2 ± 0.5 kg/m) were retrieved from a database. All participants were healthy, nonsmoker and free of medication. Available data included metabolic profile, muscle sympathetic nervous activity (MSNA, microneurography), endothelial function (pulse amplitude tonometry, augmentation index), estimated glomerular filtration rate (eGFR) and echocardiography., Results: With participants grouped into sex-adjusted tertiles of SUA, those in the third tertile of SUA had increased waist circumference, worse metabolic profile (fasting glucose, total cholesterol, triglycerides and HDL), elevated MSNA, decreased endothelial function, increased augmentation index and decreased eGFR compared with those in the first tertile of SUA. In multiple regression analysis adjusted for age, sex, BMI and ethnicity, SUA was independently associated with waist circumference, low-density lipoprotein, triglycerides, augmentation index, MSNA and eGFR, providing a combined adjusted R = 0.599 or 60% of the overall variance., Conclusion: In a healthy population with a high proportion of obesity, SUA is associated with measures of metabolic, end-organ damage and sympathetic tone indicating the potential value of SUA as a marker of early cardiovascular disease development.

Introduction: Obesity and type 2 diabetes mellitus are increasing worldwide, reaching pandemic proportions. The understanding of the role of functional restriction and gut hormones can be a beneficial tool in treating obesity and diabetes. However, the exact hormonal profiles in different metabolic states and surgical models are not known., Methods and Analysis: The HIPER-1 Study is a single-centre cross-sectional study in which 240 patients (in different metabolic states and surgical models) will receive an oral mixed-meal tolerance test (OMTT). At baseline and after 30, 60 and 120 min, peptide YY and glucagon-like peptide 1 levels and glucose and insulin sensitivity will be measured. The primary end point of the study will be the area under the glucagon-like peptide 1 and peptide YY curves after the OMTT. Secondary study end points will include examination of the difference in plasma levels of the distal ileal hormones in subjects with various health statuses and in patients who have been treated with different surgical techniques., Ethics and Dissemination: An independent ethics committee, the Institutional Review Board of Istanbul Sisli Kolan International Hospital, Turkey, has approved the study protocol. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders., Trial Registration Number: NCT02532829; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Eligibility criteria for bariatric surgery in diabetes include BMI ≥35 kg/m(2) and poorly controlled glycemia. However, BMI does not predict diabetes remission, and thus, predictors need to be identified., Research Design and Methods: Seven hundred twenty-seven patients were included in a database merged from the Swedish Obese Subjects (SOS) study and two randomized controlled studies, with 415 surgical and 312 medical patients in total. Bariatric operations were divided into gastric only (GO) and gastric plus diversion (GD)., Results: Sixty-four percent of patients in the surgical arm and 15.0% in the medical arm experienced diabetes remission (P < 0.001). GO yielded 60% remission, and GD yielded 76% remission. The best predictors of diabetes remission were lower baseline glycemia and shorter diabetes duration. However, when operation type was considered, GD predicted a higher likelihood of remission and greater weight loss. Patients in remission (responders) lost more weight (25% vs. 17%) and waist circumference (18% vs. 13%) and experienced better insulin sensitivity than nonresponders., Conclusions: Surgery is more effective than medical treatment in achieving diabetes remission and tighter glycemic control. Shorter diabetes duration, lower fasting glycemia before surgery, and GD versus GO procedures independently predict higher rates of remission, whereas baseline HbA1c and waist circumference predict improved glycemic control. The results show the advantage of an early operation together with better controlled glycemia on diabetes remission independently of BMI., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Polycystic ovary syndrome (PCOS) is a common endocrine condition underpinned by insulin resistance and associated with increased risk of obesity, type 2 diabetes and adverse cardiovascular risk profile. Previous data suggest autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction in PCOS. However, it is not clear whether these abnormalities are driven by obesity and metabolic disturbance or whether they are independently related to PCOS., Participants and Methods: We examined multiunit and single-unit muscle SNS activity (by microneurography), HRV (time and frequency domain analysis) and endothelial function [ischaemic reactive hyperaemia index (RHI) using the EndoPAT device] in 19 overweight/obese women with PCOS (BMI: 31·3 ± 1·5 kg/m(2), age: 31·3 ± 1·6 years) and compared them with 21 control overweight/obese women (BMI: 33·0 ± 1·4 kg/m(2), age: 28·2 ± 1·6 years) presenting a similar metabolic profile (fasting total, HDL and LDL cholesterol, glucose, triglycerides, insulin sensitivity and blood pressure)., Results: Women with PCOS had elevated multiunit muscle SNS activity (41 ± 2 vs 33 ± 3 bursts per 100 heartbeats, P < 0·05). Single-unit analysis showed that vasoconstrictor neurons were characterized by elevated firing rate and probability and incidence of multiple spikes (P < 0·01 for all parameters). Women with PCOS also had impaired endothelial function (RHI: 1·77 ± 0·14 vs 2·18 ± 0·14, P < 0·05). HRV did not differ between the groups., Conclusion: Women with PCOS have increased sympathetic drive and impaired endothelial function independent of obesity and metabolic disturbances. Sympathetic activation and endothelial dysfunction may confer greater cardiovascular risk in women with PCOS., (© 2015 John Wiley & Sons Ltd.)

Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C-C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response.

Background: The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program., Methods: Seventeen non-smoking, un-medicated individuals aged 55 ± 1 years (mean ± SEM), body mass index (BMI) 33.9 ± 1.7 kg/m(2), underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted as controls. Insulin sensitivity and insulin clearance were assessed via euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin extraction was calculated as fasting C-peptide to insulin ratio (endogenous insulin clearance); SNS activity was quantified by microneurographic nerve recordings of muscle sympathetic nerve activity (MSNA) and whole-body norepinephrine kinetics; and vascular function by calf venous occlusion plethysmography and finger arterial tonometry., Results: Weight loss averaged -8.3 ± 0.6% of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilization (by 20 ± 9%, P = 0.04) and exogenous insulin clearance (by 12 ± 5%, P = 0.02). Hepatic insulin extraction increased from 6.3 ± 0.8 to 7.1 ± 0.9 (P = 0.09). Arterial norepinephrine concentration decreased by -12 ± 5%, whole-body norepinephrine spillover rate by -14 ± 8%, and MSNA by -9 ± 5 bursts per 100 heartbeats in the HCD group (P all >0.05 versus control group). Step-wise regression analysis revealed a bidirectional relationship between enhanced exogenous insulin clearance post weight loss and reduction in calf vascular resistance (r = -0.63, P = 0.01) which explained 40% of the variance. Increase in hepatic insulin extraction was predicted by enhanced finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose tolerance (P = 0.002) which together explained 64% of the variance., Conclusions: Insulin clearance is independently and reciprocally associated with changes in vascular function during weight loss intervention. Trial registration ClinicalTrials.gov: NCT01771042 and NCT00408850.

The sympathetic nervous system (SNS) plays a key role in both cardiovascular and metabolic regulation; hence, disturbances in SNS regulation are likely to impact on both cardiovascular and metabolic health. With excess adiposity, in particular when visceral fat accumulation is present, sympathetic activation commonly occurs. Experimental investigations have shown that adipose tissue releases a large number of adipokines, cytokines, and bioactive mediators capable of stimulating the SNS. Activation of the SNS and its interaction with adipose tissue may lead to the development of hypertension and end-organ damage including vascular, cardiac, and renal impairment and in addition lead to metabolic abnormalities, especially insulin resistance. Lifestyle changes such as weight loss and exercise programs considerably improve the cardiovascular and metabolic profile of subjects with obesity and decrease their cardiovascular risk, but unfortunately weight loss is often difficult to achieve and sustain. Pharmacological and device-based approaches to directly or indirectly target the activation of the SNS may offer some benefit in reducing the cardiometabolic consequences of obesity. Preliminary evidence is encouraging, but more trials are needed to investigate whether sympathetic inhibition could be used in obesity to reverse or prevent cardiometabolic disease development. The purpose of this review article is to highlight the current knowledge of the role that SNS plays in obesity and its associated metabolic disorders and to review the potential benefits of sympathoinhibition on metabolic and cardiovascular functions., (Copyright © 2015 the American Physiological Society.)

Context: Insulin resistance is associated with blunted sympathetic nervous system (SNS) response to carbohydrate ingestion which may contribute to postprandial hypotension and impaired body weight homeostasis., Objective: This study was conducted to examine the effects of pharmacological insulin sensitization on whole-body norepinephrine kinetics during a standard 75-g oral glucose tolerance test (OGTT) in obese, insulin resistant subjects with metabolic syndrome., Methods: Un-medicated individuals (n=42, mean age 56±0.8 yrs, body mass index 34±0.6 kg/m(2)) were randomised to 12-weeks pioglitazone (PIO, 15 mg for 6 weeks, then 30 mg daily) or placebo using a double-blind, parallel group design. Whole-body norepinephrine kinetics (arterial norepinephrine concentration, calculated spillover and clearance rates), spontaneous cardiac baroreflex sensitivity, heart rate and blood pressure were measured at times 0, 30, 60, 90 and 120 minutes during OGTT. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M) and Matsuda index., Results: PIO increased clamp derived glucose utilisation by 35% (P<0.001) and there were concurrent reductions in inflammatory status and plasma triglycerides (P<0.05). Fasting norepinephrine kinetic parameters were unaltered. PIO treatment was associated with lower plasma insulin incursions, greater reduction in diastolic blood pressure and enhanced baroreflex sensitivity during OGTT (P all <0.05). The overall norepinephrine spillover response (AUC(0-120)) increased significantly in the PIO group (group × time interaction, P=0.04), with greatest increment at 30 minutes post-glucose (101±38 ng/min at baseline versus 241±48 ng/min post treatment, P=0.04) and correlated with percent improvement in M., Conclusions: PIO enhances the early postprandial SNS response to carbohydrate ingestion., (Copyright © 2015. Published by Elsevier Inc.)

Introduction: There is a paucity of data examining the effects of weight change on knee joint structures and symptoms. This study examined the effect of weight change on change in knee cartilage volume and symptoms in an obese cohort., Methods: 112 obese subjects (Body Mass Index ≥30 kg/m(2)) were recruited from various community sources to examine the effect of obesity on musculoskeletal health. Tibial cartilage volume, determined by MRI, and knee symptoms, determined by the Western Ontario and McMaster Osteoarthritis Index (WOMAC) were collected at baseline and an average of 2.3 years later., Results: Percentage weight change was associated with change in medial tibial cartilage volume (β -1.2 mm(3), 95% CI -2.3 to -0.1 mm(3), p=0.03) that was consistent throughout the spectrum of weight loss through to mild weight gain. Percentage weight change was not associated with change in the lateral tibial (p=0.93) or patella (p=0.32) cartilage volumes. Percentage weight change was associated with change in all WOMAC subscales (all p≤0.01): pain (β -1.8 mm, 95% CI -3.2 to -0.4 mm), stiffness (β -1.6 mm, 95% CI -2.5 to -0.7 mm) and function (β -6.9 mm, 95% CI -11.6 to -2.1 mm)., Conclusions: The linearity of effect implies that weight loss is associated with reduced medial cartilage volume loss and improved knee symptoms, while weight gain is associated with increased medial cartilage volume loss and worse knee symptoms. These results suggest that in obese people, small amounts of weight change may have the potential for a disease modifying effect on both knee joint structure and symptoms. While weight loss is an important primary management strategy in obese individuals, avoidance of further weight gain should also be a clinical goal., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Context: Impaired insulin clearance contributes to the hyperinsulinemia of obesity, yet relatively little is known concerning the pathophysiological determinants of insulin clearance in obese populations., Objective: To examine the cross-sectional relationship between insulin clearance and resting sympathetic nervous system activity in a cohort of obese subjects with metabolic syndrome., Participants and Methods: Unmedicated, nonsmoking subjects (31 male, 27 female; aged 56 ± 1 year; body mass index 33.7 ± 0.6 kg/m(2)) underwent euglycemic hyperinsulinemic clamp to determine insulin sensitivity (M) and insulin clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry, Doppler echocardiography, and oral glucose tolerance test., Results: Univariate correlation analyses showed inverse associations between insulin clearance and arterial norepinephrine concentration (r = -0.44, P = .0006), calculated norepinephrine spillover rate (r = -0.33, P = .01), augmentation index (AI, r = -0.37, P = .005), and positive associations with M (r = 0.30, P = .02), Matsuda insulin sensitivity index (r = 0.27, P = .04), and cardiac output (r = 0.27, P = .04). Insulin clearance and sensitivity did not differ between genders, however females had higher AI compared to males (35 ± 3% versus 14 ± 2%, P < .001). In age and gender adjusted stepwise regression analyses, arterial norepinephrine concentration alone explained 19% of the variance in insulin clearance. When all significant variables were entered into the regression model, arterial norepinephrine, AI, gender, and M were independent predictors of insulin clearance, together explaining 41% of the variance., Conclusions: Arterial norepinephrine concentration is inversely and independently associated with whole-body insulin clearance rate in obese individuals with metabolic syndrome. Prospective studies are needed to determine the direction of causality and the chronology of interactions between insulin clearance and sympathetic neural activity.

There is concern that intentional weight loss may generate excessive loss of fat-free mass (FFM). Idealists target minimal loss of FFM, while others consider that FFM loss of up to 25% of weight loss is acceptable. In a cross-sectional study of 275 weight-stable, overweight or obese adults, we used whole-body dual-energy X-ray absorptiometry to measure FFM. A range of models was used to estimate the expected ΔFFM/Δweight ratio required to attain the body composition of a weight-stable individual at a lower body mass index (BMI). Higher BMI was associated linearly with higher FFM in men and women. Proportional ΔFFM/Δweight was influenced by sex, BMI and age. Direct scatter plot analysis, quadratic curve fit modelling and linear FFM-BMI modelling provided similar estimates for each model of ΔFFM/Δweight ratio, with 40% for men and 33% for women. These results show that the 25% rule is inappropriate and our estimates are higher than those generally reported after intentional weight loss indicating favourable preservation of FFM., (© 2014 John Wiley & Sons Ltd.)

The 'obesity paradox' refers to observations that run counter to the thesis that normal weight (BMI 18.5-24.9 g/m(2)) provides the lowest mortality and higher weight is associated with greater mortality. We argue that the weight of lowest mortality is influenced by aging and chronic disease, with mortality advantage extending into the overweight and even class I obese ranges under some circumstances. A focus on quality nutrition, physical activity, fitness, and maintaining function in these weight ranges may be preferable to a focus on intentional weight loss, which has uncertain effects. The 'obesity paradox' is no 'paradox' if one defines and interprets 'ideal' weight appropriately.

Context: Insulin resistance and sympathetic nervous system overactivity are closely associated and contribute to cardiovascular risk., Objective: The objective of the study was to test the hypotheses that pharmacological improvement in insulin sensitivity would (1) attenuate sympathetic neural drive and (2) enhance neuronal norepinephrine uptake., Participants and Methods: A randomized, double-blind trial was conducted in 42 obese, unmedicated individuals with metabolic syndrome (mean age 56 ± 1 y, body mass index 34 ± 0.6 kg/m(2)) who received 12 weeks of pioglitazone (PIO; 15 mg for 6 wk, then 30 mg daily) or matched placebo. Clinical measurements included whole-body norepinephrine kinetics [spillover rate, plasma clearance, and the steady state ratio of tritiated 3,4-dihydroxyphenylglycol to tritiated norepinephrine ([(3)H]-DHPG to [(3)H]-NE) as an index of neuronal uptake-1], muscle sympathetic nerve activity, spontaneous baroreflex sensitivity, euglycemic hyperinsulinemic clamp, oral glucose tolerance test, ambulatory blood pressure, and Doppler echocardiography., Results: PIO treatment increased glucose uptake by 35% and was accompanied by significant reductions in diastolic blood pressure and improved left ventricular diastolic and endothelial function. Resting muscle sympathetic nerve activity burst frequency decreased by -6 ± 3 burst/min compared with baseline (P = .03), but the magnitude of change was not different from placebo (P = .89). Norepinephrine spillover and clearance rates and baroreflex sensitivity were unchanged. Post hoc subgroup analyses revealed an 83% increase in [(3)H]-DHPG to [(3)H]-NE ratio in hyperinsulinemic (P = .04) but not normoinsulinemic subjects (time × group interaction, P = .045). Change in [(3)H]-DHPG to [(3)H]-NE ratio correlated with improvements in diastolic blood pressure (r = -0.67, P = .002), the ratio of early (E) to late (A) peak transmitral diastolic inflow velocity (r = 0.62, P = .008), E wave deceleration time (r = -0.48, P = .05), and Δinsulin area under the curve0-120 during the oral glucose tolerance test (r = -0.42, P = .08)., Conclusions: Compared with placebo, PIO does not affect resting sympathetic drive or norepinephrine disposition in obese subjects with metabolic syndrome. Treatment induced changes in the [(3)H]-DHPG to [(3)H]-NE ratio related to reduction in hyperinsulinemia and improvements in diastolic function.

Background: The concept that androgens regulate multiple aspects of adipose tissue metabolism in women is based on studies of women with pathological androgen excess and in vitro studies generally using supraphysiological androgen concentrations. We investigated whether in women with normal-range serum testosterone, relationships exist between serum androgens and expression of proinflammatory (tumor necrosis factor-α, interleukin-6, CD68), anti-inflammatory (adiponectin), and lipid metabolic (lipoprotein lipase, hormone sensitive lipase) genes in omental adipose tissue, and severity of nonalcoholic fatty liver disease (NAFLD)., Methods: We studied obese women undergoing laparoscopic gastric band surgery (premenopausal, regular menses, nondiabetic, serum testosterone <2.5 nmol/L, n=27). Gene expression was measured in omental adipose tissue. Liver biopsies were examined in 22 participants., Results: Serum testosterone or androstanediol glucuronide (an indicator of peripheral androgen metabolism) were not related to markers of inflammation or lipid metabolism in omental adipose tissue. In women with NAFLD, there was a significant trend to higher serum free testosterone, serum insulin, and insulin resistance with increasing severity of liver pathology; however, markers of inflammation in omental adipose tissue did not differ. Omental lipoprotein lipase expression was significantly increased in women with nonalcoholic steatohepatitis (NASH)., Conclusions: These primarily correlative data suggest that physiological-range androgen levels do not influence inflammation or lipid metabolism in omental adipose tissue of women, but further studies of direct androgen effects on adipose tissue are needed for confirmation. Androgens may still play a role in the pathogenesis of NAFLD in women, via mechanisms unrelated to omental adipose tissue metabolism.

Background: Obesity is associated with impairments of physical function, cardiovascular fitness, muscle strength and the capacity to perform activities of daily living. This review examines the specific effects of exercise training in relation to body composition and physical function demonstrated by changes in cardiovascular fitness, and muscle strength when obese adults undergo energy restriction., Methods: Electronic databases were searched for randomised controlled trials comparing energy restriction plus exercise training to energy restriction alone. Studies published to May 2013 were included if they used multi-component methods for analysing body composition and assessed measures of fitness in obese adults., Results: Fourteen RCTs met the inclusion criteria. Heterogeneity of study characteristics prevented meta-analysis. Energy restriction plus exercise training was more effective than energy restriction alone for improving cardiovascular fitness, muscle strength, and increasing fat mass loss and preserving lean body mass, depending on the type of exercise training., Conclusion: Adding exercise training to energy restriction for obese middle-aged and older individuals results in favourable changes to fitness and body composition. Whilst weight loss should be encouraged for obese individuals, exercise training should be included in lifestyle interventions as it offers additional benefits.

Objective: To describe the baseline characteristics in patients who chose placement of a LAP-BAND AP® System (LBAP) and participated in the Helping Evaluate Reduction in Obesity (HERO) Study across regions., Patients and Methods: HERO is a five-year, prospective, multicenter, international study of patients with LBAP placement between July 22, 2009 and January 31, 2011. In addition to baseline and peri-surgery clinical data, seven follow up visits are scheduled at 3, 6 and 12 months, and annually through year five. Data collection included family and medical history, clinical outcomes, laboratory data, health-related quality of life (HRQoL), productivity, healthcare resource utilization, and adverse events., Results: LBAP were placed in 1106 enrolled patients; 56.6% from the US, 26.3% from Europe, 7.1% from Canada, and 10.0% from Australia. The majority were female (n = 877 (79.3%)) with a mean age of 43 years (s.d. = 11.4) and mean body mass index of 45.1 kg/m(2) (s.d. = 6.9). The most common comorbidities were hypertension (HTN) (overall  = 42.9%) and diabetes (overall 22.2%, with 27% from the US and 14% from Europe). Overall, less than 5% had a history of cardiovascular disease. The prevalence rates of HTN, diabetes and cardiovascular disease were significantly (p<0.001) higher in men than in women across all regions. Overall HRQoL also worsened with increasing BMI., Conclusions: The HERO study is the first large, multinational and long-term registry with the LBAP. This study will provide real-world outcomes data on LAGB that will help inform patient choice, clinician treatment strategies, and payer reimbursement decisions.

Objective: Foot pain is a common complaint in adults. Increased BMI and fat mass have been linked only to foot pain prevalence. Therefore, a longitudinal study to examine the relationship between body composition and incident foot pain over 3 years was conducted., Design and Methods: Sixty-one community dwelling participants from a previous study of musculoskeletal health, who did not have foot pain at study inception in 2008, were invited to take part in this follow-up study in 2011. Current foot pain was determined using the Manchester Foot Pain and Disability Index, and body composition was measured using dual X-ray absorptiometry at study baseline., Results: Of the 51 respondents (84% response rate, 37 females and 14 males), there were 11 who developed foot pain. BMI ranged from underweight to morbidly obese (17-44 kg/m2), mean 27.0 ± 6.0 kg/m2. Incident foot pain was positively associated with both fat mass (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03-1.20) and fat-mass index (OR 1.28, 95% CI 1.04-1.57) in multivariate analysis., Conclusions: Fat mass is a predictor of incident foot pain. This study supports the notion that incident foot pain in overweight individuals is associated with fat mass rather than body mass alone., (Copyright © 2013 The Obesity Society.)

Aim: To examine the emotional well-being of severely obese Australians with type 2 diabetes, along with markers of social and economic disadvantage, using the Diabetes MILES - Australia dataset., Methods: Diabetes MILES - Australia was a national survey of 3338 adults with diabetes that focused on psychosocial issues; 1795 had type 2 diabetes and reported BMI. We extracted data regarding depression (PHQ-9), anxiety (GAD-7), obesity- and diabetes-related comorbidities, and demographics. The severely obese group (SOG) (BMI ≥ 35; median BMI=41.6) constituted 530 (30%) of the type 2 diabetes respondents and was matched with 530 controls (CG) (BMI<35; median BMI=28.2). Within- and between-group trends were examined., Results: The SOG had higher depression scores (median (IQR) 6.0 (3-12)) than CG (5.0 (2-10)); p<0.001, and were more likely to report moderate-severe depressive symptoms (37% versus 27%; p<0.001). The groups did not differ on anxiety. The SOG, compared with the CG, were more likely to live alone (21% versus 17%), receive a disability pension (21% versus 15%), earn ≤$40.000/year (51% versus 41%; all p<0.05), and were less likely to be employed (46% versus 53%), university or higher educated (17% versus 26%), or have health insurance (50% versus 60%; all p ≤ 0.01). Moderate-severe depression was positively associated with cumulative stressors of severe obesity, socioeconomic disadvantage, and obesity- and diabetes-related comorbidity., Conclusions: Severely obese people living with type 2 diabetes have cumulative stressors related to health, disability, demographic and socioeconomic factors, and impaired emotional well-being., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: It is well recognised that Australia has one of the highest prevalences of overweight and obesity in the developed world, and that this is the greatest contributing factor, along with ageing, to the chronic disease burden in our society. Predictions are confronting; close to 80% of Australian adults are predicted by be obese by the year 2025. The determinants of obesity are multifactorial and are influenced by early life environments as well as genetics. Prevention is failing due to many factors including a poor understanding of these determinants as well as reluctance to act at a government/community level., Objective: This article aims to provide a practical approach to weight management in general practice with a focus on some of the more intensive interventions beyond the first line lifestyle modification advice., Discussion: General practitioners are often well placed to identify overweight and obesity. Patient engagement in management is critical, as for any chronic disease. Treatment needs to be evidence based and focused on a broad range of health outcomes, not simply on weight. Intensive interventions to potentiate weight loss may involve use of very low energy diets, pharmacotherapy and bariatric surgery. Referral to specialist weight assessment and management clinics, where available may be appropriate, particularly for complex cases with more severe comorbidity.

Objective: The molecular mechanisms underpinning the loss of skeletal muscle mass and strength associated with insulin resistance remain to be extensively investigated. There is mounting recognition that certain ligands of the transforming growth factor (TGF)-β family are upregulated in insulin resistant states, including obesity. This study analyses the expression of potent ligands of this family, TGF-β1 and myostatin (MSTN) and downstream components of the canonical TGF-β family signaling pathway (Smads) in skeletal muscle from lean and insulin resistant obese subjects., Design and Methods: Biopsies taken from the rectus abdominis muscle of lean (n = 13) and obese subjects (n = 20) were analyzed for the expression of TGF-β1 and MSTN as well as TGF-β signaling components, Smad2, 3, and 4, and transcription of the muscle regulatory factors (MRFs), MyoD and myogenin., Results: Increases in Smad2 and Smad3 phosphorylation, Smad4 and total Smad3 were observed to be coincident with altered transcription of MyoD and myogenin. TGF-β1 and MSTN protein levels were not significantly altered., Conclusion: Thus, increased Smad signaling is likely to account for, at least, a proportion of obesity and insulin resistance-related muscle atrophy through reduced MRF, particularly MyoD, transcription. The major regulatory ligand may not be MSTN and further members of the TGF-β1 superfamily should be considered., (Copyright © 2012 The Obesity Society.)

Context: Altered cardiac structure and function have been reported in prediabetic and diabetic populations; however, the contribution of the sympathetic nervous system (SNS) to these changes has yet to be delineated., Objective: Our objective was to examine interrelationships between glucose metabolism, left ventricular mass and function, and SNS activity in obese metabolic syndrome subjects., Participants and Methods: Unmedicated impaired glucose tolerant (IGT) (n = 31) or treatment-naive type 2 diabetic (T2D) (n = 25) subjects, matched for age (mean 58 ± 1 years), gender, body mass index (32.2 ± 0.5 kg/m(2)), and blood pressure, participated. They underwent echocardiography and assessments of whole-body norepinephrine kinetics, muscle sympathetic nerve activity, and insulin sensitivity by euglycemic clamp (M value)., Results: T2D subjects had higher left ventricular mass index (LVMI) (93.6 ± 3.5 vs 77.2 ± 3.4 g/m(2), P = .002) and Doppler-derived isovolumetric relaxation and deceleration times (both P < .05) and lower early/late transmitral inflow velocities (E/A) (P = .02) compared with IGT. Total muscle sympathetic nerve activity and arterial norepinephrine concentration were higher in the T2D group (by 18% and 32%, respectively, both P ≤ .05), whereas plasma norepinephrine clearance was reduced (1.94 ± 0.11 vs 2.26 ± 0.10 L/min, P = .02). M value correlated inversely with left ventricular septal thickness (r = -0.46, P = .007). Whole-body noradrenaline spillover rate correlated with LVMI in the T2D subgroup (r = 0.47, P = .03). In the pooled cohort, LVMI was independently predicted by pulse pressure (r = 0.38, P = .004) and E/A ratio by 2-hour glucose (r = -0.38, P = .005)., Conclusions: Transition from IGT to T2D is associated with cardiac enlargement and diastolic dysfunction, which relate to metabolic, hemodynamic, and SNS alterations.

Objective: To examine the longitudinal association between significant weight change and change in knee symptoms (pain, stiffness, and function), and to determine whether the effects differ in those who are obese and those with osteoarthritis (OA)., Methods: Two hundred fifty subjects ranging from normal weight to obese (body mass index range 16.9-59.1 kg/m(2) ) and no significant musculoskeletal disease were recruited from the general community and weight loss clinics and organizations. Seventy-eight percent were followed at ~2 years. Weight, height, and knee symptoms (using the Western Ontario and McMaster Universities Osteoarthritis Index) were assessed at baseline and followup. Any weight loss methods were recorded., Results: Thirty percent of subjects lost ≥5% of baseline weight, 56% of subjects' weight remained stable (loss or gain of <5% of baseline weight), and 14% of subjects gained ≥5% of baseline weight. Using estimated marginal means, weight gain was associated with worsening pain (mean 27.1 mm; 95% confidence interval [95% CI] -1.1, 55.2), stiffness (mean 18.4 mm; 95% CI 1.5, 35.3), and function (mean 99.3 mm; 95% CI 4.0, 194.6) compared to stable weight. Weight loss was associated with reduced pain (mean -22.4 mm; 95% CI -44.4, -0.3), stiffness (mean -15.3 mm; 95% CI -28.50, -2.0), and function (mean -73.2 mm; 95% CI -147.9, 1.3) compared to stable weight., Conclusion: Weight gain was associated with adverse effects on knee symptoms, particularly in those who are obese and who have OA. Although losing weight is potentially beneficial for symptom improvement, the effects were more modest. Avoiding weight gain is important in managing knee symptoms., (Copyright © 2013 by the American College of Rheumatology.)

Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility), structural and functional properties of carotid arteries respectively, are early markers, as well as strong predictors of cardiovascular disease (CVD). The characteristic of these two parameters in individuals with BMI>40.0 kg/m(2) (Class III obesity), however, are largely unknown. The present study was designed to document cIMT and distensibility in this population and to relate these to other factors with established association with CVD in obesity. The study included 96 subjects (65 with BMI>40.0 kg/m(2) and 31, age- and gender-matched, with BMI of 18.5 to 30.0 kg/m(2)). cIMT and distensibility were measured by non-invasive high resolution ultrasonography, circulatory CD133(+)/KDR(+) angiogenic cells and endothelial microparticles (EMP) by flow cytometry, and plasma levels of adipokines, growth factors and cytokines by Luminex immunoassay kits. The study results demonstrated increased cIMT (0.62±0.11 mm vs. 0.54±0.08 mm, P = 0.0002) and reduced distensibility (22.52±10.79 10(-3)kpa(-1)vs. 29.91±12.37 10(-3)kpa(-1), P<0.05) in individuals with BMI>40.0 kg/m(2). Both cIMT and distensibility were significantly associated with traditional CVD risk factors, adiposity/adipokines and inflammatory markers but had no association with circulating angiogenic cells. We also demonstrated, for the first time, elevated plasma EMP levels in individuals with BMI>40.0 kg/m(2). In conclusion, cIMT is increased and distensibility reduced in Class III obesity with the changes predominantly related to conventional CVD risk factors present in this condition, demonstrating that both cIMT and distensibility remain as CVD markers in Class III obesity.

Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m(2)), and family history of diabetes were studied. We measured resting muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state glucose utilization adjusted for fat-free mass and steady-state insulin concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA burst incidence (67 ± 4 versus 55 ± 3 bursts per 100 heartbeats; P = 0.05) and arterial norepinephrine levels (264 ± 33 versus 167 ± 16 pg/mL; P = 0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover, norepinephrine spillover responses to glucose ingestion were blunted in T2D subjects. The M/I value independently predicted whole-body norepinephrine spillover (r = -0.47; P = 0.008), whereas fasting insulin level related to neuronal norepinephrine reuptake (r = -0.35, P = 0.047). These findings demonstrate that progression to T2D is associated with increased central sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine disposition.

Context: Obstructive sleep apnea (OSA) is strongly related to obesity. Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA., Objective: To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA., Design, Setting, and Patients: A randomized controlled trial of 60 obese patients (body mass index: >35 and <55) with recently diagnosed (<6 months) OSA and an apnea-hypopnea index (AHI) of 20 events/hour or more. These patients had been prescribed continuous positive airway pressure (CPAP) therapy to manage OSA and were identified via accredited community sleep clinics. The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical researchers in Melbourne, Australia. Patients with obesity hypoventilation syndrome, previous bariatric surgery, contraindications to bariatric surgery, or significant cardiopulmonary, neurological, vascular, gastrointestinal, or neoplastic disease were excluded., Interventions: Patients were randomized to a conventional weight loss program that included regular consultations with a dietitian and physician, and the use of very low-calorie diets as necessary (n = 30) or to bariatric surgery (laparoscopic adjustable gastric banding; n = 30)., Main Outcome Measures: The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to randomization. Secondary outcomes were changes in weight, CPAP adherence, and functional status., Results: Patients lost a mean of 5.1 kg (95% CI, 0.8 to 9.3 kg) in the conventional weight loss program compared with 27.8 kg (95% CI, 20.9 to 34.7 kg) in the bariatric surgery group (P < .001). The AHI decreased by 14.0 events/hour (95% CI, 3.3 to 24.6 events/hour) in the conventional weight loss group and by 25.5 events/hour (95% CI, 14.2 to 36.7 events/hour) in the bariatric surgery group. The between-group difference was -11.5 events/hour (95% CI, -28.3 to 5.3 events/hour; P = .18). CPAP adherence did not differ between the groups. The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score (mean, 9.3 [95% CI, 0.5 to 18.0]; P = .04)., Conclusion: Among a group of obese patients with OSA, the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss., Trial Registration: anzctr.org Identifier: 12605000161628.

Bariatric surgery provides substantial, sustained weight loss and major improvements in glycaemic control in severely obese individuals with type 2 diabetes. However, uptake of surgery in eligible patients is poor, and the barriers are difficult to surmount. We examine the indications for and efficacy and safety of conventional bariatric surgical procedures and their effect on glycaemic control in type 2 diabetes. How surgical gastrointestinal interventions achieve these changes is of great research interest, and is evolving rapidly. Old classifications about restriction and malabsorption are inadequate, and we explore understanding of putative mechanisms. Some bariatric procedures improve glycaemic control in people with diabetes beyond that expected for weight loss, and understanding this additional effect could provide insights into the pathogenesis of type 2 diabetes and assist in the development of new procedures, devices, and drugs both for obese and non-obese patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Context: The sympathetic nervous system is an important physiological modulator of basal and postprandial energy expenditure., Objective: Our objective was to investigate whether the variability of weight loss attained during hypocaloric dietary intervention is related to individual differences in baseline sympathetic drive and nutritional sympathetic nervous system responsiveness., Participants and Methods: Untreated obese subjects (n = 42; body mass index = 32.1 ± 0.5 kg/m(2)), aged 57 ± 1 yr, who fulfilled Adult Treatment Panel III metabolic syndrome criteria participated in a 12-wk weight loss program using a modified Dietary Approaches to Treat Hypertension (DASH) diet. Muscle sympathetic nerve activity (MSNA) was measured by microneurography at rest and in a subset of subjects during a standard 75-g oral glucose tolerance test., Results: Weight loss (6.7 ± 0.5 kg) was independently predicted by baseline resting MSNA burst incidence (r = 0.38; P = 0.019), which accounted for 14.3% of the variance after adjustment for age and baseline body weight. Weight loss-resistant subjects in the lower tertile of weight loss (4.4 ± 0.3%) had significantly blunted MSNA responses to oral glucose at baseline compared with successful weight losers (9.6 ± 0.8%). Absolute Δ MSNA averaged -7 ± 2, -6 ± 5, and -3 ± 3 bursts per 100 heartbeats at 30, 60, and 90 min after glucose in the weight loss-resistant group. Corresponding values in the successful weight loss group were 9 ± 3, 12 ± 3, and 15 ± 4 bursts per 100 heartbeats (time × group interaction, P = 0.004)., Conclusions: These findings indicate that baseline sympathetic drive and nutritional sympathetic responsiveness may be important prognostic biological markers for weight loss outcome.

Objective: To examine the relationship between obesity, body composition, and foot pain as assessed by the Manchester Foot Pain and Disability Index (MFPDI)., Methods: Subjects 25-62 years of age (n = 136) were recruited as part of a study examining the relationship between obesity and musculoskeletal health. Foot pain was defined as current foot pain and pain in the last month, and an MFPDI score of ≥1. Body composition (tissue mass and fat distribution) was measured using dual x-ray absorptiometry., Results: The body mass index (BMI) in this population was normally distributed around a mean of 32.1 kg/m(2). The prevalence of foot pain was 55.1%. There was a positive association between BMI and foot pain (odds ratio [OR] 1.11, 95% confidence interval [95% CI] 1.06-1.17). Foot pain was also positively associated with fat mass (OR 1.05, 95% CI 1.02-1.09) and fat mass index (FMI; OR 1.16, 95% CI 1.06-1.28) when adjusted for age, sex, and skeletal muscle mass and age, sex, and fat-free mass index (FFMI), respectively. When examining fat distribution, positive associations were observed for android/total body fat ratio (OR 1.42, 95% CI 1.11-1.83) and android/gynoid fat ratio (OR 35.15, 95% CI 2.60-475.47), although gynoid/total body fat ratio was inversely related to foot pain (OR 0.83, 95% CI 0.73-0.93). Skeletal muscle mass and FFMI were not associated with foot pain when adjusted for fat mass or FMI, respectively., Conclusion: Increasing BMI, specifically android fat mass, is strongly associated with foot pain and disability. This may imply both biomechanical and metabolic mechanisms., (Copyright © 2012 by the American College of Rheumatology.)

Aim: Insulin resistance and visceral adiposity are predisposing factors for fatty liver disease. The main objectives of this study were (i) to compare the effects of caloric restriction (CR) alone or together with moderate-intensity aerobic exercise training (CR+EX) on liver enzymes, a surrogate marker of liver injury, in obese metabolic syndrome (MetS) subjects and (ii) to identify anthropometric, metabolic, cardiovascular and dietary predictors of changes in liver enzymes., Methods: Sedentary men and women (n = 63), aged 55 ± 6 (s.d.) years with body mass index 32.7 ± 4.1 kg/m(2) and confirmed MetS, were randomized to 12-week CR, CR+EX or no treatment (Control)., Results: Weight loss averaged 7.6% in the CR and 9.1% in the CR+EX group (time effect, p < 0.001; group effect, p = 0.11); insulin sensitivity improved by 49 and 45%, respectively (both p < 0.001). Fitness (maximal oxygen consumption) increased by 19% in the CR+EX group only (p < 0.001). Alanine aminotransferase (ALT) levels decreased by 20% in the CR and 24% in the CR+EX group (time effect, both p < 0.001; group effect, p = 0.68); corresponding values for γ-glutamyltransferase (GGT) were -28 and -33%, respectively (time effect, both p < 0.001; group effect, p = 0.28). Reduction in abdominal fat mass (measured by DXA from L1 to L4) independently predicted ΔALT (r = 0.42, p = 0.005) and ΔGGT (r = 0.55, p < 0.001), whereas change in dietary saturated fat intake was independently associated with ΔALT (r = 0.35, p = 0.03)., Conclusions: Reductions in central adiposity and saturated fat intake are key drivers of improvement in liver enzymes during lifestyle interventions. Exercise training did not confer significant incremental benefits in this study., (© 2011 Blackwell Publishing Ltd.)

Eating behaviors impact satiety and caloric intake so should be considered in any weight-loss program. A novel custom-made oral device has been designed to be worn in the upper palate while eating in order to slow eating-rate and aid weight loss. The aim of this study was to assess the device's potential impact on weight-loss and gain first impressions among overweight/obese Australians. Twenty participants (M: 6, F: 14, mean age 36 years, BMI 27-33 kg/m(2)) were enrolled in a 4-month open-label trial. Each received a device and nutritionist-delivered diet plan. Weight, compliance, and acceptability were assessed fortnightly. Anthropometry, biochemical and clinical outcomes were measured at baseline and 16 weeks. Sixteen participants completed the study. Mean weight-loss was 4.9 ± 0.9 kg, or 5.2 ± 0.9% initial bodyweight (P < 0.001, n = 20, intention-to-treat). There were no significant adverse events (AEs), but 65% of participants required device adjustment by the dentist. Compliance (defined as >5 uses/week) was achieved by 80% of participants and correlated positively with weight-loss (R = 0.68, P = 0.001). All reported that the device was comfortable and reduced bite-size, promoted chewing and slowed eating-rate. Most observed either no change, or increased satiety, despite reduced meal sizes. For most, speech difficulties discouraged device use in social settings. All reported greater awareness of food choices, portion sizes and eating-rate. Subjective control of dietary behaviors, measured by the Three Factor Eating Questionnaire (TFEQ), improved significantly. The device should be explored as an adjunct to dietary composition change in weight-management programs, to assist patients to modify eating behaviors and achieve successful weight-loss.

Background: Unknown hormonal and neural satiety signals are thought to drive sustainable weight loss following laparoscopic adjustable gastric banding (LAGB). The objective of this study was to investigate whether the structurally related satiety hormones pancreatic polypeptide (PP) and peptide YY (PYY) influence total percentage weight loss after LAGB., Methods: A cross-sectional study examined 17 postoperative individuals who had already achieved a mean of 28% LAGB-induced weight loss (range, 10-38%). A prospective study assessed plasma PP and PYY meal responses in 16 obese individuals prior to LAGB., Results: In the cross-sectional study, individuals with higher weight loss had lower PP meal responses (2-h AUC, R = -0.60, p = 0.01) and lower fasting PYY levels (R = -0.55, p = 0.02). In the prospective study, subsequent mean weight loss was 20% (range, 5-50%) after a mean of 53 months. Low preoperative PP meal response (2-h AUC) predicted significantly higher subsequent weight loss after LAGB (R = -0.56, p = 0.024). The eight individuals with the lowest PP meal response lost more weight than the eight with the highest PP meal response (median 25% vs. 14%, p = 0.004). When compared across all three groups, mean PP meal responses did not differ. Fasting PYY levels, however, were significantly lower in the postoperative group compared to the group tested pre-operatively, or the BMI-matched controls (-30%, p = 0.03)., Conclusions: PYY appears reduced in proportion to weight loss following LAGB, possibly representing attempted orexigenic homeostatic compensation. Although PP responses appear unchanged by weight loss status, low PP meal response may predict higher weight loss. PP meal response may be a biological marker that could predict an individual's susceptibility to the mechanism underlying LAGB-induced weight loss.

The International Diabetes Federation Taskforce on Epidemiology and Prevention of Diabetes convened a consensus working group of diabetologists, endocrinologists, surgeons and public health experts to review the appropriate role of surgery and other gastrointestinal interventions in the treatment and prevention of Type 2 diabetes. The specific goals were: to develop practical recommendations for clinicians on patient selection; to identify barriers to surgical access and suggest interventions for health policy changes that ensure equitable access to surgery when indicated; and to identify priorities for research. Bariatric surgery can significantly improve glycaemic control in severely obese patients with Type 2 diabetes. It is an effective, safe and cost-effective therapy for obese Type 2 diabetes. Surgery can be considered an appropriate treatment for people with Type 2 diabetes and obesity not achieving recommended treatment targets with medical therapies, especially in the presence of other major co-morbidities. The procedures must be performed within accepted guidelines and require appropriate multidisciplinary assessment for the procedure, comprehensive patient education and ongoing care, as well as safe and standardized surgical procedures. National guidelines for bariatric surgery need to be developed for people with Type 2 diabetes and a BMI of 35 kg/m² or more.

Bariatric surgery, through its efficacy and improved safety, is emerging as an important and broadly available treatment for people with severe and complex obesity that has not responded adequately to other therapy. Established procedures, such as Roux-en-Y gastric bypass and adjustable gastric banding, account for more than 80% of bariatric surgical procedures globally. Sleeve gastrectomy has emerged as a stand-alone procedure. Truly malabsoptive procedures, such as biliopancreatic diversion and its duodenal switch variant, have a diminishing role as primary procedures, but remain an option for patients who do not respond adequately to less disruptive procedures. The procedures vary considerably in their postoperative morbidity and mortality; pattern and extent of weight loss; nature and severity of long-term complications; and nutritional requirements and risks. There is no perfect procedure--an informed risk and benefit assessment should be made by each patient. Gastroenterologists also need to be familiar with the risks and benefits of current and emerging procedures as they are likely to be increasingly involved in the integrated care of these patients.