How do people living with obesity who use obesity services perceive healthcare professionals' representation of the disease on social media? An interpretative phenomenological analysis.

OBJECTIVES: The objective of this study was to explore how people living with obesity who use obesity services perceive healthcare professionals' (HCPs) online representation of the disease on social media. By exploring their perspective, we aimed to develop a framework to inform good practice around social media use for HCPs. DESIGN: This was a qualitative study using a phenomenological framework. Following in-depth semi-structured interviews, analysis was undertaken to identify superordinate themes relating to how HCPs portray living with obesity online. SETTING: Patient advocacy organisation (The Irish Coalition for People Living with Obesity) and three clinical sites offering obesity treatment in Ireland. PARTICIPANTS: 15 adult participants comprising of 12 women and 3 men who use social media and are living with obesity and who use obesity services. RESULTS: Three key themes of how people living with obesity who use obesity services perceive HCP's online representation of the disease. (1) Negative experiences of HCPs-participants describe encountering weight stigma and bias on social media from HCPs that they characterised as simplistic and outdated conceptualisations. These engender shame, fear and anger. (2) Positive experience of HCPs-participants report social media allows HCPs to educate and inform public perception of obesity. Positive online experiences lead to feelings of inclusion, understanding and encouragement. (3) Expectations of HCPs-qualifications, professional titles and academic association affected the perceived trustworthiness of information and its impact on readers. Participants feel there is a duty of care for HCPs in obesity medicine to advocate and be active online to provide accurate medical information. CONCLUSION: HCP's use of social media has a powerful impact on people with obesity who use healthcare and obesity services. Social media is a key tool in obesity awareness and education. We propose the '3E' framework-Empower, Evidence-Based and Educate and be educated to guide HCPs' social media use.

Predicting antipsychotic-induced weight gain in first episode psychosis - A field-wide systematic review and meta-analysis of non-genetic prognostic factors.

BACKGROUND: Whether non-genetic prognostic factors significantly influence the variable prognosis of antipsychotic-induced weight gain (AIWG) has not yet been systematically explored. METHODS: Searches for both randomized and non-randomized studies were undertaken using four electronic databases, two trial registers, and via supplemental searching methods. Unadjusted and adjusted estimates were extracted. Meta-analyses were undertaken using a random-effects generic inverse model. Risk of bias and quality assessments were undertaken using Quality in Prognosis Studies (QUIPS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. RESULTS: Seventy-two prognostic factors were assessed across 27 studies involving 4426 participants. Only age, baseline body mass index (BMI), and sex were suitable for meta-analysis. Age (b=-0.044, 95%CI -0.157-0.069), sex (b=0.236, 95%CI -0.086-0.558), and baseline BMI (b=-0.013 95%CI -0.225-0.200) were associated with nonsignificant effects on AIWG prognosis. The highest quality GRADE rating was moderate in support of age, trend of early BMI increase, antipsychotic treatment response, unemployment, and antipsychotic plasma concentration. Trend of early BMI increase was identified as the most clinically significant prognostic factor influencing long-term AIWG prognosis. CONCLUSIONS: The strong prognostic information provided by BMI trend change within 12 weeks of antipsychotic initiation should be included within AIWG management guidance to highlight those at highest risk of worse long-term prognosis. Antipsychotic switching and resource-intensive lifestyle interventions should be targeted toward this cohort. Our results challenge previous research that several clinical variables significantly influence AIWG prognosis. We provide the first mapping and statistical synthesis of studies examining non-genetic prognostic factors of AIWG and highlight practice, policy, and research implications.

Antigen specific T cells in people with obesity at five months following ChAdOx1 COVID-19 vaccination.

BACKGROUND/OBJECTIVES: People with obesity (PWO) face an increased risk of severe outcomes from COVID-19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID-19 adenovirus vector vaccination. SUBJECTS/METHODS: We investigated SARS-CoV-2 specific T cell responses in 50 subjects, five months following a two-dose primary course of ChAdOx1 nCoV-19 (AZD1222) vaccination. We further divided our cohort into PWO (n = 30) and matched controls (n = 20). T cell (CD4+, CD8+) cytokine responses (IFNγ, TNFα) to SARS-CoV-2 spike peptide pools were determined using multicolour flow cytometry. RESULTS: Circulating T cells specific for SARS-CoV-2 were readily detected across our cohort, with robust responses to spike peptide stimulation across both T cell lines. PWO and controls had comparable levels of both CD4+ and CD8+ SARS-CoV-2 spike specific T cells. Polyfunctional T cells - associated with enhanced protection against viral infection - were detected at similar frequencies in both PWO and controls. CONCLUSIONS: These data indicate that PWO who have completed a primary course of ChAdOx1 COVID-19 vaccination have robust, durable, and functional antigen specific T cell immunity that is comparable to that seen in people without obesity.

Multidimensional pain profiling in people living with obesity and attending weight management services: a protocol for a longitudinal cohort study.

INTRODUCTION: Pain is prevalent in people living with overweight and obesity. Obesity is associated with increased self-reported pain intensity and pain-related disability, reductions in physical functioning and poorer psychological well-being. People living with obesity tend to respond less well to pain treatments or management compared with people living without obesity. Mechanisms linking obesity and pain are complex and may include contributions from and interactions between physiological, behavioural, psychological, sociocultural, biomechanical and genetic factors. Our aim is to study the multidimensional pain profiles of people living with obesity, over time, in an attempt to better understand the relationship between obesity and pain. METHODS AND ANALYSIS: This longitudinal observational cohort study will recruit (n=216) people living with obesity and who are newly attending three weight management services in Ireland. Participants will complete questionnaires that assess their multidimensional biopsychosocial pain experience at baseline and at 3, 6, 12 and 18 months post-recruitment. Quantitative analyses will characterise the multidimensional pain experiences and trajectories of the cohort as a whole and in defined subgroups. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics and Medical Research Committee of St Vincent's Healthcare Group, Dublin, Ireland (reference no: RS21-059) and the University College Dublin Human Research Ethics Committee (reference no: LS-E-22-41-Hinwood-Smart). Findings will be disseminated through peer-reviewed journals, conference presentations, public and patient advocacy groups, and social media. STUDY REGISTRATION: Open Science Framework Registration DOI: https://doi.org/10.17605/OSF.IO/QCWUE.

Obesity in Adults: A 2022 Adapted Clinical Practice Guideline for Ireland.

BACKGROUND: This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. SUMMARY: It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. KEY MESSAGES: People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay.

Guidelines for treating child and adolescent obesity: A systematic review.

Obesity is a chronic disease that compromises the physical and mental health of an increasing proportion of children globally. In high-income countries, prevalence of paediatric obesity is increasing faster in those from marginalised populations such as low-income households, suggesting the disease as one that is largely systemic. Appropriate treatment should be prioritised in these settings to prevent the development of complications and co-morbidities and manage those that already exist. An array of clinical practice guidelines are available for managing overweight and obesity in children and adolescents, but no systematic review has yet compared their quality or synthesised their recommendations. We aimed to narratively review clinical practice guidelines published in English for treating child and adolescent obesity, to identify the highest quality guidelines, and assess similarities, conflicts, and gaps in recommendations. We systematically searched academic databases and grey literature for guidelines published. We used the AGREE II tool to assess the quality, and identified nine high quality guidelines for inclusion in a narrative review of recommendations. Guidelines predominantly recommended the delivery of multi-component behaviour-change interventions aimed at improving nutrition and physical activity. Treatment outcomes were generally focussed on weight, with less emphasis on managing complications or improving quality-of-life. There was no evidence-based consensus on the best mode of delivery, setting, or treatment format. The guidelines rarely included recommendations for addressing the practical or social barriers to behaviour change, such as cooking skills or supervised physical activity. There is insufficient evidence to evaluate pharmaceutical and surgical interventions in children, and these were generally not recommended. It should be noted that this review addressed documents published in English only, and therefore the included guidelines were applicable predominantly to high-resource settings.

Metformin in the management of antipsychotic-induced weight gain in adults with psychosis: development of the first evidence-based guideline using GRADE methodology.

BACKGROUND: Adjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin's place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication. OBJECTIVE: To produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology. METHODS: A list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be 'adopted or adapted' from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008-2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. FINDINGS: We confirmed that no published guideline-of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs. CONCLUSION: All 11 recommendations and 7 supporting good practice developed here were formulated de novo. CLINICAL IMPLICATIONS: These recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.

The Association of Physical Function Measures With Frailty, Falls History, and Metabolic Syndrome in a Population With Complex Obesity.

Background: Frailty, falls and metabolic syndrome are known to be associated with poorer physical function. This study builds on available research by further investigating the relationship between physical function measures, including those comprising frailty, with metabolic syndrome (MetS) and falls, in the context of complex obesity. Methods: Participants were recruited from the national Level 3 weight management service in Ireland. A retrospective audit of data gathered at initial assessment was performed. Data included past medical history, blood tests, blood pressure measurement, anthropometrics, falls history, self-reported physical activity levels (PALs) and physical function measures, including hand grip strength (HGS), "timed up and go" (TUG), functional reach (FR), sit to stand (STS) and gait speed. A modified version of the Fried Frailty Index was employed. Results: Of the 713 participants, 65.1% (n = 464) were female and 34.9% (n = 249) were male with a mean age of 44.2 (±11.7) years and body mass index (BMI) of 50.6 kg/m2 (±8.2). Frailty was identified in 3.4% (n = 24), falls in 28.8% (n = 205) and MetS in 55.1% (n = 393). Frailty was associated with older age (53.8 ± 14.3 vs. 43.9 ± 11.5 years), poorer PALs (27.29 ± 46.3 vs. 101.1 ± 147.4 min/wk), reduced grip strength (17.7 ± 4.6 vs. 34.2 ± 11.0 Kg) longer STS (21.7 ± 6.6 vs. 13.7 ± 5.7 s), shorter functional reach (29.7 ± 7.9 vs. 37.9 ± 8.2 cm) and slower gait speed (0.6 ± 0.2 vs. 1.1 ± 0.5 m/s). Those reporting a falls history had a reduced FR (35.8 ± 8.9 vs. 38.3 ± 7.8 cm) and slower STS (15.4 ± 8.0 vs. 13.3 ± 4.7 s). Participants with MetS had lower PALs (83.2 ± 128.2 vs. 119.2 ± 157.6) and gait speed (1.1 ± 0.3 vs. 1.2 ± 0.7 m/s). There was no difference in BMI between fallers and non-fallers (51.34 ± 8.44 vs. 50.33 ± 8.13 Kg/m2, p = 0.138), nor between those with or without MetS. Significant associations were found between BMI and all physical function measures except the TUAG. Conclusion: The associations between frailty, falls and MetS and their combined impact on physical function in people living with obesity demonstrates the need for appropriate screening. Utilising grip strength and gait speed to identify frailty in those with obesity and metabolic syndrome could help target therapies aimed at improving strength, physical function and ultimately quality of life.

Influence of diabetes on natriuretic peptide thresholds in screening for Stage B heart failure.

CONTEXT: Natriuretic peptide (NP) has been shown to be an effective screening tool to identify patients with Stage B heart failure and to have clinical value in preventing heart failure progression. The impact of associated metabolic confounders on the screening utility of NP needs clarification. OBJECTIVE: To assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic Stage B heart failure. MATERIALS AND METHODS: The study population consisted of 1368 asymptomatic patients with cardiovascular risk factors recruited from general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at point-of-care. RESULTS: BNP was found to be as accurate for detecting Stage B heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78] and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are required to achieve the same level of diagnostic sensitivity in DM compared with non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is required for patients with DM. CONCLUSION: Although a significantly different BNP threshold is detected for patients with DM, the BNP concentration difference is small and unlikely to warrant a clinically different diagnostic threshold.

Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity.

Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance. MAIT cells were enriched in adipose tissue (AT) compared with blood. AT MAIT cells, but not circulating MAIT cells, were capable of producing IL-10. In AT from obese subjects, MAIT cells were depleted, were less likely to produce IL-10, and more frequently produced IL-17. Finally, we show that IL-17(+) MAIT cells are also increased in childhood obesity, and altered MAIT cell frequencies in obese children are positively associated with insulin resistance. These data indicate that MAIT cells are enriched in human AT and display an IL-17(+) phenotype in both obese adults and children, correlating with levels of insulin resistance. The alterations in MAIT cells may be contributing to obesity-related sterile inflammation and insulin resistance.

Cystic fibrosis related diabetes.

Improved life expectancy in cystic fibrosis (CF) has led to an expanding population of adults with CF, now representing almost 50 % of the total CF population. This creates new challenges from long-term complications such as diabetes mellitus (DM), a condition that is present in 40 %-50 % of adults with CF. Cystic fibrosis-related diabetes (CFRD) results from a primary defect of insulin deficiency and although sharing features with type 1 (DM1) and type 2 diabetes (DM2), it is a clinically distinct condition. Progression to diabetes is associated with poorer CF clinical outcomes and increased mortality. CFRD is not associated with an increased risk of cardiovascular disease and the prevalence of microvascular complications is lower than DM1 or DM2. Rather, the primary goal of insulin therapy is the preservation of lung function and optimization of nutritional status. There is increasing evidence that appropriate screening and early intervention with insulin can reverse weight loss and improve pulmonary function. This approach may include targeting postprandial hyperglycemia not detected by standard diagnostic tests such as the oral glucose tolerance test. Further clinical research is required to guide when and how much to intervene in patients who are already dealing with the burden of one chronic illness.

The impact of childhood obesity on inflammation, innate immune cell frequency, and metabolic microRNA expression.

BACKGROUND: Obesity is characterized by chronic inflammation, immune dysregulation, and alteration of gene expression, associated with type 2 diabetes mellitus and cardiovascular disease. The degree to which these changes occur in childhood obesity is not fully defined. AIMS AND METHODS: The aim was to investigate the effect of childhood obesity on immune cell frequency, macrophage activation, cytokine production, and specific regulators of metabolic gene expression. Profiling was performed on peripheral blood from 29 obese and 20 nonobese children using real-time PCR, ELISA, and flow cytometry. RESULTS: Fasting glucose was similar in both groups, but there was a higher degree of insulin resistance in obese subjects (homeostasis model of assessment for insulin resistance, 4.8 vs 0.84; P < .001). Soluble CD163, a marker of macrophage polarization to a proinflammatory profile, was elevated in the obese compared to nonobese children (135 vs 105 ng/mL; P = .03). Invariant natural killer T cells were reduced in the obese children (CD3 T cells, 0.31 vs 0.53%; P = .001). Cytokine profiling revealed significantly elevated TNF-α (6.7 vs 5.1 pg/mL; P = .01) and leptin (1186 vs 432 pg/mL; P < .001) and reduced adiponectin (884 vs 1321 pg/mL; P = .001) in obese compared to nonobese children. Stimulation of peripheral blood mononuclear cells from obese children resulted in higher levels of IL-1ß (2100 vs 1500 pg/mL; P = .018). There was a 4-fold increase in expression of microRNA33a (P = .001) and a 3-fold increase in microRNA33b (P = .017) in obese children. CONCLUSION: Childhood obesity is associated with changes in immune cell frequency, inflammatory environment, and regulation of metabolic gene expression. These changes have been causally linked to the onset of metabolic disease in adulthood and suggest the future trajectory of obese children to the development of type 2 diabetes mellitus and premature cardiovascular disease.

Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1α-dependent inflammation.

Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody responses to a level comparable to Freund's incomplete adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1α-dependent recruitment of neutrophils and M1-like macrophages, while simultaneously diminishing M2-like macrophages. We found that endogenous oils from subcutaneous and omental adipocytes, and from healthy and unhealthy obese individuals, promoted comparable inflammatory responses. Furthermore, we also confirmed that white adipocytes in visceral fat of metabolically unhealthy obese (MUO) individuals are significantly larger than those in metabolically healthy obese individuals. Since adipocyte size is positively correlated with adipocyte death, we propose that endogenous oils have a higher propensity to be released from hypertrophied visceral fat in MUO individuals and that this is the key factor in driving inflammation. In summary, this study shows that adipocytes contain a potent oil adjuvant which drives IL-1α-dependent proinflammatory responses in vivo.

Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Glucagon-like peptide 1 (GLP-1) is a gut hormone used in the treatment of type 2 diabetes mellitus. There is emerging evidence that GLP-1 has anti-inflammatory activity in humans, with murine studies suggesting an effect on macrophage polarisation. We hypothesised that GLP-1 analogue therapy in individuals with type 2 diabetes mellitus would affect the inflammatory macrophage molecule soluble CD163 (sCD163) and adipocytokine profile. METHODS: We studied ten obese type 2 diabetes mellitus patients starting GLP-1 analogue therapy at a hospital-based diabetes service. We investigated levels of sCD163, TNF-α, IL-1ß, IL-6, adiponectin and leptin by ELISA, before and after 8 weeks of GLP-1 analogue therapy. RESULTS: GLP-1 analogue therapy reduced levels of the inflammatory macrophage activation molecule sCD163 (220 ng/ml vs 171 ng/ml, p < 0.001). This occurred independent of changes in body weight, fructosamine and HbA1c. GLP-1 analogue therapy was associated with a decrease in levels of the inflammatory cytokines TNF-α (264 vs 149 pg/ml, p < 0.05), IL-1ß (2,919 vs 748 pg/ml, p < 0.05) and IL-6 (1,379 vs 461 pg/ml p < 0.05) and an increase in levels of the anti-inflammatory adipokine adiponectin (4,480 vs 6,290 pg/ml, p < 0.002). CONCLUSIONS/INTERPRETATION: In individuals with type 2 diabetes mellitus, GLP-1 analogue therapy reduces the frequency of inflammatory macrophages. This effect is not dependent on the glycaemic or body weight effects of GLP-1.

Cigarette smoke alters the invariant natural killer T cell function and may inhibit anti-tumor responses.

Invariant natural killer T (iNKT) cells are a minor subset of human T cells which express the invariant T cell receptor Vα24 Jα18 and recognize glycolipids presented on CD1d. Invariant NKT cells are important immune regulators and can initiate anti-tumor responses through early potent cytokine production. Studies show that iNKT cells are defective in certain cancers. Cigarette smoke contains many carcinogens and is implicated directly and indirectly in many cancers. We investigated the effects of cigarette smoke on the circulating iNKT cell number and function. We found that the iNKT cell frequency is significantly reduced in cigarette smoking subjects. Invariant NKT cells exposed to cigarette smoke extract (CSE) showed significant defects in cytokine production and the ability to kill target cells. CSE inhibits the upregulation of CD107 but not CD69 or CD56 on iNKT cells. These findings suggest that CSE has a specific effect on iNKT cell anti-tumor responses, which may contribute to the role of smoking in the development of cancer.

The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity.

OBJECTIVE: Several studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity. SUBJECTS: Thirty-five patients undergoing bariatric surgery were classified as MHO (n = 15) or metabolically unhealthy obese (MUO, n = 20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40-71). RESULTS: There was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r = 0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9+/-10.9 microm) when compared with metabolically unhealthy patients (100.0+/-7.6 microm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1+/-8.5 microm versus 107.9+/-7.1 microm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r = 0.66, p<0.0001 and r = 0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis. CONCLUSION: Metabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health, and possibly progression from hepatic steatosis to fibrosis.

BMI > or = 50 kg/m2 is associated with a younger age of onset of overweight and a high prevalence of adverse metabolic profiles.

OBJECTIVE: To study the demographic and clinical parameters of three different categories of obesity, with particular focus on a cohort of individuals with BMI > or = 50 kg/m2, the fastest growing category of obesity. DESIGN: Over 700 obese individuals were studied (186 with BMI = 30-39 kg/m2, 316 with BMI = 40-49 kg/m2 and 290 with BMI > or = 50 kg/m2). RESULTS: Median BMI was 51 kg/m2 for patients who reported onset of overweight before 15 years of age, 47 kg/m2 for patients who reported onset between 15 and 30 years, and 42 kg/m2 for patients who became overweight after 30 years of age. The BMI > or = 50 kg/m2 group was notably younger than the group with BMI = 30-39 kg/m2 (44 (SD 11) years v. 50 (SD 15) years; P < 0.0001). Eighteen per cent of obese patients studied were considered metabolically healthy according to standard cut-off points for blood pressure, fasting glucose and lipid profiles. However, the proportion of metabolically healthy individuals was significantly higher in the BMI = 30-39 kg/m2 group than in the BMI = 40-49 kg/m2 and BMI > or = 50 kg/m2 groups (31% v. 17% and 12% respectively; P < 0.05 and P < 0.005). When compared with people of similar age in the general population, individuals with BMI > or = 50 kg/m2 had lower rates of marriage (51% v. 72%) and a higher prevalence of unemployment (14% v. 5%). CONCLUSIONS: The current study suggests that the increasing prevalence of childhood obesity worldwide will lead to many more individuals achieving a higher BMI at a younger age. Furthermore, an earlier onset of overweight does not appear to prevent the adverse metabolic health outcomes associated with extreme obesity.

Are natural killer cells protecting the metabolically healthy obese patient?

With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight-management clinic and 11 lean healthy controls. Patients were classified into metabolically "healthy obese" (n = 26; mean age 42.6 years, mean BMI 46.8 kg/m(2)) or "unhealthy obese" (n = 26; mean age 45 years, mean BMI 47.5 kg/m(2)) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.