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Background: The relationship between body size and cardiovascular events is complex. This study utilized the ADVANCE (Assessing Diagnostic Value of Noninvasive FFR CT in Coronary Care) Registry to investigate the association between body mass index (BMI), coronary artery disease (CAD), and clinical outcomes. Methods: The ADVANCE registry enrolled patients undergoing evaluation for clinically suspected CAD who had >30% stenosis on cardiac computed tomography angiography. Patients were stratified by BMI: normal 2 , overweight 25–29.9 kg/m 2 , and obese ≥30 kg/m 2 . Baseline characteristics, cardiac computed tomography angiography and computed tomography fractional flow reserve (FFR CT ), were compared across BMI groups. Adjusted Cox proportional hazards models assessed the association between BMI and outcomes. Results: Among 5014 patients, 2166 (43.2%) had a normal BMI, 1883 (37.6%) were overweight, and 965 (19.2%) were obese. Patients with obesity were younger and more likely to have comorbidities, including diabetes and hypertension (all P P CT , was similar across BMI categories (63.4% obese, 66.1% overweight, and 67.8% normal BMI; P =0.07). Additionally, patients with obesity had a lower coronary volume-to-myocardial mass ratio compared with patients who were overweight or had normal BMI (obese BMI, 23.7; overweight BMI, 24.8; and normal BMI, 26.3; P P >0.05). Conclusions: Patients with obesity in the ADVANCE registry were less likely to have anatomically obstructive CAD by cardiac computed tomography angiography but had a similar degree of physiologically significant CAD by FFR CT and similar rates of adverse events. An exclusively anatomic assessment of CAD in patients with obesity may underestimate the burden of physiologically significant disease that is potentially due to a significantly lower volume-to-myocardial mass ratio.

ObjectivesGiant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are age-associated inflammatory diseases that frequently overlap. Both diseases require long-term treatment with glucocorticoids (GCs), often associated with comorbidities. Previous population-based cohort studies reported that an unhealthier metabolic profile might prevent the development of GCA. Here, we report metabolic features before start of treatment and during treatment in patients with GCA and PMR.MethodsIn the Dutch GCA/PMR/SENEX (GPS) cohort, we analysed metabolic features and prevalence of comorbidities (type 2 diabetes, hypercholesterolaemia, hypertension, obesity and cataract) in treatment-naïve patients with GCA (n=50) and PMR (n=42), and compared those with the population-based Lifelines cohort (n=91). To compare our findings in the GPS cohort, we included data from patients with GCA (n=52) and PMR (n=25) from the Aarhus cohort. Laboratory measurements, comorbidities and GC use were recorded for up to 5 years in the GPS cohort.ResultsGlycated haemoglobin levels tended to be higher in treatment-naïve patients with GCA, whereas high-density lipoprotein, low-density lipoprotein and cholesterol levels were lower compared with the Lifelines population. Data from the Aarhus cohort were aligned with the findings obtained in the GPS cohort. Presence of comorbidities at baseline did not predict long-term GC requirement. The incidence of diabetes, obesity and cataract among patients with GCA increased upon initiation of GC treatment.ConclusionData from the GCA and PMR cohorts imply a metabolic dysregulation in treatment-naïve patients with GCA, but not in patients with PMR. Treatment with GCs led to the rise of comorbidities and an unhealthier metabolic profile, stressing the need for prednisone-sparing targeted treatment in these vulnerable patients.

Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance. This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality. Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter. Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery.

Objective: To identify body mass index (BMI) trajectories in adult life and to examine their association with endometrial cancer (EC) risk, also exploring whether relations differ by hormonal replacement therapy use. Design: Pooled analysis of two case–control studies. Setting: Italy and Switzerland. Population: A total of 458 EC cases and 782 controls. Methods: We performed a latent class growth model to identify homogeneous BMI trajectories over six decades of age, with a polynomial function of age. Odds ratios (ORs) and the corresponding 95% CI for EC risk were derived through a multiple logistic regression model, correcting for classification error. Main outcome measures: The relation of BMI trajectories with endometrial cancer. Results: We identified five BMI trajectories. Compared with women in the ‘Normal weight-stable’ trajectory, a reduction by about 50% in the risk of EC emerged for those in the ‘Underweight increasing to normal weight’ (95% CI 0.28–0.99). The ‘Normal weight increasing to overweight’ and the ‘Overweight-stable’ trajectories were associated with, respectively, an excess of 3% (95% CI 0.66–1.60) and of 71% (95% CI 1.12–2.59) in cancer risk. The OR associated to the trajectory ‘Overweight increasing to obese’ was 2.03 (95% CI 1.31–3.13). Stronger effects emerged among hormonal replacement therapy never users (OR 2.19 for the ‘Overweight-stable’ trajectory and OR 2.49 for the ‘Overweight increasing to obese’ trajectory). Conclusions: Our study suggests that longer exposure to overweight and obesity across a lifetime is associated with an increased risk of endometrial cancer. Weight during adulthood also appears to play an important role. Tweetable abstract: Longer exposure to overweight and obesity across a lifetime is associated with an increased risk of endometrial cancer.

Hyperglycemia is the commonest medical condition affecting pregnancy and its incidence is increasing globally in parallel with the twin epidemics of diabetes and obesity. Both pre-pregnancy diabetes and gestational diabetes are associated with short term pregnancy complications, with the risk of immediate complications generally broadly rising with more severe hyperglycemia. In this article we firstly consider these risks and their optimal management during pregnancy and then broaden our scope to consider the long-term implications of hyperglycemia in pregnancy as it relates to overall maternal and offspring health in a life course perspective.

The modification of physical activity (PA) on the metabolic status in relation to atrial fibrillation (AF) in obesity remains unknown. We aimed to investigate the independent and joint associations of metabolic status and PA with the risk of AF in obese population. Based on the data from UK Biobank study, we used Cox proportional hazards models for analyses. Metabolic status was categorized into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). PA was categorized into four groups according to the level of moderate-to-vigorous PA (MVPA): none, low, medium, and high. A total of 119,424 obese participants were included for analyses. MHO was significantly associated with a 35% reduced AF risk compared with MUO (HR = 0.65, 95% CI: 0.57–0.73). No significant modification of PA on AF risk among individuals with MHO was found. Among the MUO participants, individuals with medium and high PA had significantly lower AF risk compared with no MVPA (HR = 0.84, 95% CI: 0.74–0.95, and HR = 0.87, 95% CI: 0.78–0.96 for medium and high PA, respectively). As the severity of MUO increased, the modification of PA on AF risk was elevated accordingly. To conclude, MHO was significantly associated with a reduced risk of AF when compared with MUO in obese participants. PA could significantly modify the relationship between metabolic status and risk of AF among MUO participants, with particular benefits of PA associated with the reduced AF risk as the MUO severity elevated.

This review focuses on communication about weight-related issues with patients with obesity in general practice. Primary care providers still lack knowledge and tools to address and communicate about the topic of weight and weight-related issues - with focus on minimizing stigmatization and a person centered approach. A few communication tools on the topic have been developed but it seems that the use of those is limited, suggesting an urgent need for making a fast, easy and simple tool for the use in general practice.

The prevalence of obesity increases rapidly, in all ages and in all social classes. Epidemiological studies have documented that obesity have large long-term consequences, even in children, including development of metabolic syndrome and other obesity-associated comorbidities (i.e. diabetes mellitus type 2, cancer and cardiovascular diseases) which may largely impact the person's health, life expectancy, and quality of life. As summarised in this review, epidemiological studies add to our knowledge on comorbidities associated with obesity, the prognosis, and the prevalence of obesity over time.

BACKGROUND: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England.METHODS: In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m 2) after vaccination. FINDINGS: Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m 2), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70-83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41-0·63]; healthy weight: 0·34 [0·32-0·36]; overweight: 0·32 [0·30-0·34]; and obesity: 0·32 [0·30-0·34]) and death (underweight: 0·60 [0·36-0·98]; healthy weight: 0·39 [0·33-0·47]; overweight: 0·30 [0·25-0·35]; and obesity: 0·26 [0·22-0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose. INTERPRETATION: Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (FUNDING: UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.

The present study was undertaken to assess whether the odds for incident radiographic osteoarthritis (OA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers 1 and 2 years prior, and whether the presence of inflammation on MRI differs between normal-weight and overweight/obese individuals who develop radiographic OA up to 4 years prior. We studied 355 knees from the Osteoarthritis Initiative study that developed incident radiographic OA and 355 matched controls. MRIs were read for effusion-synovitis and Hoffa-synovitis for up to 4 consecutive annual time points. Subjects were classified as normal-weight (BMI

Objective: This study aimed to review the literature comparing full-term induction of labor with expectant management in women with obesity on the risk of cesarean delivery and other adverse outcomes.Data sources: A literature search was performed on PubMed, EMBASE, Scopus, ClinicalTrials.gov, and the Cochrane Library. This study had no time, language, or geographic restriction.Study eligibility criteria: Studies were eligible if (1) they were cohort or randomized controlled trials, (2) they compared induction of labor at early or late term with expectant management, and (3) they included women with a body mass index of ≥30 kg/m2. Studies restricted to women with multiple pregnancy, premature rupture of membranes, or noncephalic presentation were excluded. The primary outcome was cesarean delivery. The secondary outcomes included maternal and neonatal mortality and morbidities and were evaluated.Methods: The risk of bias was assessed by 2 authors using the Risk of Bias In Non-Randomized Studies of Interventions tool. Only studies assessed with low or moderate risk of bias contributed to the meta-analysis. Data were combined to pooled relative risks and 95% confidence intervals using random effects models. The quality of evidence was assessed for selected outcomes.Results: Of the 232 studies identified, 13 were aligned with the inclusion criteria, and 4 cohort studies, including 216,318 women with induction of labor and 1,122,769 women managed expectantly, were included in the meta-analysis for the primary outcome. In women with obesity, full-term induction of labor was associated with a lower risk of cesarean delivery than expectant management (19.7% vs 24.5%; relative risk, 0.71; 95% confidence interval, 0.63-0.81). Moreover, this study found the same direction of the association for other selected outcomes: severe perineal lacerations (relative risk, 0.65; 95% confidence interval, 0.48-0.89), maternal infection (relative risk, 0.42; 95% confidence interval, 0.21-0.84), perinatal mortality (relative risk, 0.41; 95% confidence interval, 0.18-0.90), low Apgar score (relative risk, 0.48; 95% confidence interval, 0.26-0.91), meconium aspiration syndrome (relative risk, 0.40; 95% confidence interval, 0.28-0.56), and macrosomia (relative risk, 0.57; 95% confidence interval, 0.43-0.75). Conversely, induction of labor was associated with an increased risk of instrumental vaginal delivery (relative risk, 1.12; 95% confidence interval, 1.02-1.22). The quality of evidence ranged from low to very low.Conclusion: Full-term induction of labor in women with obesity may reduce the risk of cesarean delivery compared with expectant management, but the quality of the evidence is low. OBJECTIVE: This study aimed to review the literature comparing full-term induction of labor with expectant management in women with obesity on the risk of cesarean delivery and other adverse outcomes.DATA SOURCES: A literature search was performed on PubMed, EMBASE, Scopus, ClinicalTrials.gov, and the Cochrane Library. This study had no time, language, or geographic restriction.STUDY ELIGIBILITY CRITERIA: Studies were eligible if (1) they were cohort or randomized controlled trials, (2) they compared induction of labor at early or late term with expectant management, and (3) they included women with a body mass index of ≥30 kg/m 2. Studies restricted to women with multiple pregnancy, premature rupture of membranes, or noncephalic presentation were excluded. The primary outcome was cesarean delivery. The secondary outcomes included maternal and neonatal mortality and morbidities and were evaluated. METHODS: The risk of bias was assessed by 2 authors using the Risk of Bias In Non-Randomized Studies of Interventions tool. Only studies assessed with low or moderate risk of bias contributed to the meta-analysis. Data were combined to pooled relative risks and 95% confidence intervals using random effects models. The quality of evidence was assessed for selected outcomes.RESULTS: Of the 232 studies identified, 13 were aligned with the inclusion criteria, and 4 cohort studies, including 216,318 women with induction of labor and 1,122,769 women managed expectantly, were included in the meta-analysis for the primary outcome. In women with obesity, full-term induction of labor was associated with a lower risk of cesarean delivery than expectant management (19.7% vs 24.5%; relative risk, 0.71; 95% confidence interval, 0.63-0.81). Moreover, this study found the same direction of the association for other selected outcomes: severe perineal lacerations (relative risk, 0.65; 95% confidence interval, 0.48-0.89), maternal infection (relative risk, 0.42; 95% confidence interval, 0.21-0.84), perinatal mortality (relative risk, 0.41; 95% confidence interval, 0.18-0.90), low Apgar score (relative risk, 0.48; 95% confidence interval, 0.26-0.91), meconium aspiration syndrome (relative risk, 0.40; 95% confidence interval, 0.28-0.56), and macrosomia (relative risk, 0.57; 95% confidence interval, 0.43-0.75). Conversely, induction of labor was associated with an increased risk of instrumental vaginal delivery (relative risk, 1.12; 95% confidence interval, 1.02-1.22). The quality of evidence ranged from low to very low.CONCLUSION: Full-term induction of labor in women with obesity may reduce the risk of cesarean delivery compared with expectant management, but the quality of the evidence is low.

The aim of the present research was to assess the effect of bariatric surgery-induced weight loss on the tear film and ocular surface of patients with obesity. A total of 29 participants with obesity (aged 47.2 ± 10.1 years, 8 male) were measured at baseline and followed up one year after Roux-en-Y gastric bypass (RYGB) surgery. General anthropometric data, as well as serum lipid markers of cholesterol, were assessed in all individuals. Bilateral anterior eye measurements of tear meniscus height (TMH), non-invasive tear breakup time, bulbar and limbal redness and infrared meibography were captured using the Keratograph K5M (Oculus) and ocular surface damage was evaluated using fluorescein sodium and lissamine green staining. Bariatric surgery resulted in significant loss of weight (body mass index p < 0.001) and an improvement in the blood lipid profile (p < 0.01) in all participants. However, there were no statistically significant differences between the baseline and one-year follow-up for any of the measured clinical ocular surface and tear film variables (all p > 0.05). Although there were trends for a reduced TMH and a decrease in meibomian gland dropout after bariatric surgery, these differences were also insignificant (p > 0.05). In conclusion, weight reduction through bariatric surgery did not have an effect on the tear film or ocular surface in unselected patients with obesity.

Background Body mass index (BMI) has been found to be associated with a decreased risk of non-small cell lung cancer (NSCLC); however, the effect of BMI trajectories and potential interactions with genetic variants on NSCLC risk remain unknown. Methods Cox proportional hazards regression model was applied to assess the association between BMI trajectory and NSCLC risk in a cohort of 138,110 participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. One-sample Mendelian randomization (MR) analysis was further used to access the causality between BMI trajectories and NSCLC risk. Additionally, polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between BMI trajectories and genetic variants in NSCLC risk. Results Compared with individuals maintaining a stable normal BMI (n = 47,982, 34.74%), BMI trajectories from normal to overweight (n = 64,498, 46.70%), from normal to obese (n = 21,259, 15.39%), and from overweight to obese (n = 4,371, 3.16%) were associated with a decreased risk of NSCLC (hazard ratio [HR] for trend = 0.78, P < 2×10−16). An MR study using BMI trajectory associated with genetic variants revealed no significant association between BMI trajectories and NSCLC risk. Further analysis of PRS showed that a higher GWAS-identified PRS (PRSGWAS) was associated with an increased risk of NSCLC, while the interaction between BMI trajectories and PRSGWAS with the NSCLC risk was not significant (PsPRS= 0.863 and PwPRS= 0.704). In GWIA analysis, four independent susceptibility loci (P < 1×10−6) were found to be associated with BMI trajectories on NSCLC risk, including rs79297227 (12q14.1, located in SLC16A7, Pinteraction = 1.01×10−7), rs2336652 (3p22.3, near CLASP2, Pinteraction = 3.92×10−7), rs16018 (19p13.2, in CACNA1A, Pinteraction = 3.92×10−7), and rs4726760 (7q34, near BRAF, Pinteraction = 9.19×10−7). Functional annotation demonstrated that these loci may be involved in the development of NSCLC by regulating cell growth, differentiation, and inflammation. Conclusions Our study has shown an association between BMI trajectories, genetic factors, and NSCLC risk. Interestingly, four novel genetic loci were identified to interact with BMI trajectories on NSCLC risk, providing more support for the aetiology research of NSCLC. Trial registration http://www.clinicaltrials.gov, NCT01696968.

BACKGROUND & AIMS: Malnutrition is commonly seen in chronic obstructive pulmonary disease (COPD) and has been associated with negative outcomes. The objective of this study was to examine unintended weight loss (UWL) within three months, as a primary indicator for disease related malnutrition among COPD outpatients, to evaluate the prevalence of UWL, and to identify possible characteristics for UWL.METHODS: A cross-sectional study including a patient questionnaire and medical record data extraction was made with all patients visiting a Danish COPD outpatient clinic.RESULTS: Among the 200 included patients (68.7 ± 11.2 years of age), UWL was seen in 21.5%, with a median weight loss of 3.5 (2-16) kg. Underweight (BMI30 kg/m2). Reduced food intake (RFI) within the past week was experienced among 22.0% of the patients. The most common nutrition impact symptoms (NIS) were shortness of breath, reduced appetite and nausea. NIS, RFI and BMICONCLUSIONS: A high prevalence of UWL was found in COPD outpatients, and NIS and RFI as characteristics associated with UWL. Shortness of breath, reduced appetite and nausea were the most common NIS. This study found 13.5% of patients underweight, 23.5 overweight and 34.5% obese. Underweight as well as obesity may have negative consequences for the patient and the community.

Atrial fibrillation (AF) is the most common arrhythmia encountered in adults; it is associated with a significant morbidity and mortality. Obesity is a risk factor contributing to AF occurrence. Recently, interest has focused on epicardial adipose tissue (EAT), defined as a fatty deposit located between the epicardium and the visceral pericardium. Its characteristics are distinct from classic adipose deposits: it infiltrates the epicardial myocardium and secretes cytokines, which modulate cardiomyocyte electrophysiology and cardiac remodeling. Different studies show that EAT can be an independent risk factor for AF and that EAT thickness, as measured by CT or MRI, could predict the presence, severity and recurrence of AF.

Aim. Bariatric surgery improves insulin sensitivity and glucose tolerance in obese individuals with type 2 diabetes (T2D), but there is a lack of data comparing the underlying metabolic mechanisms after the 2 most common surgical procedures Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG). This study was designed to assess and compare the effects of RYGB and SG on fuel metabolism in the basal state and insulin sensitivity during a two-step euglycemic glucose clamp. Materials and Methods. 16 obese individuals with T2D undergoing either RYGB ( n = 9 ) or SG ( n = 7 ) were investigated before and 2 months after surgery, and 8 healthy individuals without obesity and T2D served as controls. All underwent a 2 h basal study followed by a 5 h 2-step hyperinsulinemic euglycemic glucose clamp at insulin infusion rates of 0.5 and 1.0 mU/kg LBM/min. Results. RYGB and SG induced comparable 15% weight losses, normalized HbA1c, fasting glucose, fasting insulin, and decreased energy expenditure. In parallel, we recorded similar increments (about 100%) in overall insulin sensitivity ( M -value) and glucose disposal and similar decrements (about 50%) in endogenous glucose production and FFA levels during the clamp; likewise, basal glucose and insulin concentrations decreased proportionally. Conclusion. Our data suggest that RYGB and SG improve basal fuel metabolism and two-step insulin sensitivity in the liver, muscle, and fat and seem equally favourable when investigated 2 months after surgery. This trial is registered with NCT02713555.

Background and Aims: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). Results: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m 2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I 2 = 0%) compared with normal BMI (18.5 to 2). Each 5 kg/m 2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I 2 = 0%). Similarly, with each 5 kg/m 2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I 2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I 2 = 0%). No associations were observed between measures of obesity and risk of UC. Conclusions: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.

Background: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known. Methods: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case–control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue nationale contre le cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Helmholtz Association, German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund (WCRF-ERC) 232997, Netherlands Government, Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Junta de Andalucia, Principality of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of OncologyICO (Spain), Swedish Cancer Society Swedish Research Council, European Commission, County Council of Skane, County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017 C19335/A21351, UK Research & Innovation (UKRI), Medical Research Council UK (MRC), European Commission 1000143 MR/M012190/1

Aims Access to total knee arthroplasty (TKA) is sometimes restricted for patients with severe obesity (BMI ≥ 40 kg/m2). This study compares the cost per quality-adjusted life year (QALY) associated with TKA in patients with a BMI above and below 40 kg/m2 to examine whether this is supported. Methods This single-centre study compared 169 consecutive patients with severe obesity (BMI ≥ 40 kg/m2) (mean age 65.2 years (40 to 87); mean BMI 44.2 kg/m2 (40 to 66); 129/169 female) undergoing unilateral TKA to a propensity score matched (age, sex, preoperative Oxford Knee Score (OKS)) cohort with a BMI < 40 kg/m2 in a 1:1 ratio. Demographic data, comorbidities, and complications to one year were recorded. Preoperative and one-year patient-reported outcome measures (PROMs) were completed: EuroQol five-dimension three-level questionnaire (EQ-5D-3L), OKS, pain, and satisfaction. Using national life expectancy data with obesity correction and the 2020 NHS National Tariff, QALYs (discounted at 3.5%), and direct medical costs accrued over a patient’s lifetime, were calculated. Probabilistic sensitivity analysis (PSA) was used to model variation in cost/QALY for each cohort across 1,000 simulations. Results All PROMs improved significantly (p < 0.05) in both groups without differences between groups. Early complications were higher in BMI ≥ 40 kg/m2: 34/169 versus 52/169 (p = 0.050). A total of 16 (9.5%) patients with a BMI ≥ 40 kg/m2 were readmitted within one year with six reoperations (3.6%) including three (1.2%) revisions for infection. Assuming reduced life expectancy in severe obesity and revision costs, TKA in patients with a BMI ≥ 40 kg/m2 costs a mean of £1,013/QALY (95% confidence interval £678 to 1,409) more over a lifetime than TKA in patients with BMI < 40 kg/m2. In PSA replicates, the maximum cost/QALY was £3,921 in patients with a BMI < 40 kg/m2 and £5,275 in patients with a BMI ≥ 40 kg/m2. Conclusion Higher complication rates following TKA in severely obese patients result in a lifetime cost/QALY that is £1,013 greater than that for patients with BMI < 40 kg/m2, suggesting that TKA remains a cost-effective use of healthcare resources in severely obese patients where the surgeon considers it appropriate. Cite this article: Bone Joint J 2022;104-B(4):452–463.

BackgroundSeveral characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19.MethodsA prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity—assessed by an increased waist–hip ratio—and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses.ResultsIn total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014).ConclusionThis study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference.Trial registration numberNL8580.

The relative risk of developing MetS is higher in patients with severe mental illness (SMI) than in the general population. Similarly, the risk of developing obesity or type 2 diabetes (T2DM) is also higher in patients with SMI. GLP-1 receptor agonists, such as liraglutide, have been shown to be effective in the treatment of T2DM and, more recently, in obesity or overweight associated with at least one metabolic disease. Their psychiatric adverse effect profiles seem to be reassuring, thus not represent a limitation for prescribing in psy chiatry. We aimed to explore the therapeutic usefulness of liraglutide in patients with psychiatric disorders associated with somatic comorbidities such as obesity, T2DM or MetS.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for identification of risk factors, which may help to identify people at enhanced risk for severe disease outcomes to improve treatment and, if possible, establish prophylactic measures. This study aimed to determine whether individuals with obesity compared to individuals with normal weight have an increased risk for severe COVID-19. We conducted a systematic literature search of PubMed, Embase and Cochrane Library and critically reviewed the secondary literature using AMSTAR-2. We explored 27 studies. Findings indicate that individuals with obesity (body mass index ≥ 30 kg/m2 ), as compared to individuals without obesity, experience an increased risk for hospitalization (odds ratio [OR]: 1.40-2.45), admission to the intensive care unit (OR: 1.30-2.32), invasive mechanical ventilation (OR: 1.47-2.63), and the composite outcome 'severe outcome' (OR or risk ratio: 1.62-4.31). We found diverging results concerning death to COVID-19, but data trended towards increased mortality. Comparing individuals with obesity to individuals without obesity, findings suggested younger individuals (

Idiopathic intracranial hypertension (IIH) is characterised by intractable headache, papilloedema, visual symptoms, pulsatile tinnitus and elevated intracranial pressure (ICP). The incidence has increased, most likely due to the simultaneous increase in obesity. This review finds that imaging is centered on ruling out structural causes of elevated ICP as well as visualising classical signs of IIH. Surgery is only indicated for patients at risk of acute vision loss and first line treatment in Denmark is optic nerve sheath fenestration, liquor drainage followed by endovascular treatment.

IntroductionThe aim of this randomised controlled trial (RCT) is to investigate whether prolonged consumption of sweeteners and sweetness enhancers (S&SEs) within a healthy diet will improve weight loss maintenance and obesity-related risk factors and affect safety markers compared with sugar.Methods and analysisSWEET (S&SEs: prolonged effects on health, obesity and safety) is a 1-year multicentre RCT including at least 330 adults with overweight (18–65 years, body mass index (BMI) >25 kg/m2) and 40 children (6–12 years, BMI-for-age >85th percentile). In an initial 2-month period, adults will consume a low-energy diet with the aim to achieve ≥5% weight loss. Children are advised to consume a generally healthy diet to maintain body weight, thus reducing their BMI-for-age z-score. In the following 10 months, participants will be randomised to follow a healthy ad libitum diet with or without S&SE products. Clinical investigations are scheduled at baseline, after 2, 6 and 12 months. The primary outcomes are body weight for efficacy and gut microbiota composition (in relation to metabolic health) for safety, both in adults. Secondary outcomes include anthropometry, risk markers for type-2 diabetes and cardiovascular diseases, questionnaires including, for example, food preferences, craving and appetite and tests for allergenicity.Ethics and disseminationThe trial protocol has been approved by the following national ethical committees; The research ethics committees of the capital region (Denmark), approval code: H-19040679, The medical ethics committee of the University Hospital Maastricht and Maastricht University (the Netherlands), approval code: NL70977.068.19/METC19-056s, Research Ethics Committee of the University of Navarra (Spain), approval code: 2019.146 mod1, Research Ethics Committee of Harokopio University (Greece), approval code: 1810/18-06-2019. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed scientific journals regardless of whether the findings are positive, negative or inconclusive.Trial registration numberNCT04226911(Clinicaltrials.gov)

Impaired mitochondrial oxidative phosphorylation (OXPHOS) in liver tissue has been hypothesised to contribute to the development of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease (NAFLD). It is unknown whether OXPHOS capacities in human visceral (VAT) and subcutaneous adipose tissue (SAT) associate with NAFLD severity and how hepatic OXPHOS responds to improvement in NAFLD. In biopsies sampled from 62 patients with obesity undergoing bariatric surgery and nine control subjects without obesity we demonstrate that OXPHOS is reduced in VAT and SAT while increased in the liver in patients with obesity when compared with control subjects without obesity, but this was independent of NAFLD severity. In repeat liver biopsy sampling in 21 patients with obesity 12 months after bariatric surgery we found increased hepatic OXPHOS capacity and mitochondrial DNA/nuclear DNA content compared with baseline. In this work we show that obesity has an opposing association with mitochondrial respiration in adipose- and liver tissue with no overall association with NAFLD severity, however, bariatric surgery increases hepatic OXPHOS and mitochondrial biogenesis.

Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots. Electronic supplementary material The online version of this article (10.1007/s00018-020-03485-z) contains supplementary material, which is available to authorized users.

ObjectiveTo evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19.DesignRetrospective, observational cohort study.MethodsWe performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes.ResultsOut of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients.ConclusionIn this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay.

Context: Obesity is associated with neuroendocrine reproductive alterations and decreased fertility. Objective: The objective of the study was to gain insight into the neuroendocrine mechanisms implicated in these alterations. Design: The effects on pulsatile LH secretion of 28 days of a hypercaloric diet were studied in lean and regularly cycling female volunteers. Approximately 50% extra calories (3 g sucrose/kg body weight per day and 1 g fat/kg body weight per day) were added to their individual daily requirements. Spontaneous and insulin-stimulated LH secretion was recorded on 2 different days, before and at the end of the caloric load. Results: The hypercaloric diet induced an average weight gain of 2.0 ± 0.3 kg (P < .05), corresponding to a body mass index increase of 0.7 ± 0.1 kg/m2 (P < .05). A concomitant decrease of 11.6% ± 4.6% in whole-body insulin sensitivity was also observed (δ = −1.6 ± 0.7 mg/kg · min glucose; P < .05). The frequency of spontaneous and insulin-stimulated pulsatile LH secretion was increased by 17.9% ± 9.0% and 26.5% ± 9.0%, respectively (both P < .05). Spontaneous LH peak amplitude was decreased by 26.5% ± 9.0% (δ = −0.7 ± 0.36 U/L; P < .05), a change correlated with insulin sensitivity. Conclusions: Short-term weight gain in normal female volunteers induces alterations of LH secretion reminiscent to those observed in obesity. A decrease in insulin sensitivity may constitute a mechanistic link between obesity and its associated neuroendocrine dysfunctions.

Compound 21 (C21), a selective agonist of angiotensin II type 2 receptor (AT2R), induces vasodilation through NO release. Since AT2R seems to be overexpressed in obesity, we hypothesize that C21 prevents the development of obesity-related vascular alterations. The main goal of the present study was to assess the effect of C21 on thoracic aorta endothelial function in a model of diet-induced obesity (DIO) and to elucidate the potential cross-talk among AT2R, Mas receptor (MasR) and/or bradykinin type 2 receptor (B2R) in this response. Five-week-old male C57BL6J mice were fed a standard (CHOW) or a high-fat diet (HF) for 6 weeks and treated daily with C21 (1 mg/kg p.o) or vehicle, generating four groups: CHOW-C, CHOW-C21, HF-C, HF-C21. Vascular reactivity experiments were performed in thoracic aorta rings. Human endothelial cells (HECs; EA.hy926) were used to elucidate the signaling pathways, both at receptor and intracellular levels. Arteries from HF mice exhibited increased contractions to Ang II than CHOW mice, effect that was prevented by C21. PD123177, A779 and HOE-140 (AT2R, Mas and B2R antagonists) significantly enhanced Ang II-induced contractions in CHOW but not in HF-C rings, suggesting a lack of functionality of those receptors in obesity. C21 prevented those alterations and favored the formation of AT2R/MasR and MasR/B2R heterodimers. HF mice also exhibited impaired relaxations to acetylcholine (ACh) due to a reduced NO availability. C21 preserved NO release through PKA/p-eNOS and AKT/p-eNOS signaling pathways. In conclusion, C21 favors the interaction among AT2R, MasR and B2R and prevents the development of obesity-induced endothelial dysfunction by stimulating NO release through PKA/p-eNOS and AKT/p-eNOS signaling pathways.

OBJECTIVE To examine the course of cardiovascular autonomic neuropathy (CAN) and related cardiometabolic risk factors in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS CAN and cardiometabolic risk factors were assessed in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) at 6-year (n = 777) and 13-year (n = 443) follow-up examinations. Cardiovascular autonomic reflex tests (CARTs)—that is, lying to standing, deep breathing, and the Valsalva maneuver—and 2-min resting heart rate variability (HRV) indices were obtained as the main measures of CAN. Risk factors related to CAN status, as determined by CARTs, were studied by using multivariate logistic regressions. The effects of risk factors on continuous CARTs and HRV indices, and their changes over time, were estimated in linear mixed models. RESULTS A progressive yet heterogeneous course of CAN occurred between the 6- and 13-year follow-ups. Higher HbA1c, weight, BMI, and triglycerides were associated with prevalent CAN. No significant effect of risk factors on CARTs was found when they were analyzed as continuous variables. CART indices decreased over time, and a trend of decreasing HRV indices was seen. Higher HbA1c and BMI were associated with lower HRV index values, but these differences diminished over time. CONCLUSIONS These data confirm that hyperglycemia, obesity, and hypertriglyceridemia are negatively related to indices of CAN, although these effects diminish over time. The observed heterogeneous course of CAN may challenge the present clinical approach of categorically classifying CARTs to diagnose CAN and the notion of CAN being irreversible.

OBJECTIVES: The aim was to examine the relationship between body mass index (BMI) and mortality in older hospitalized patients taking activities of daily living (ADLs) into account.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: Nationwide population-based study of all patients aged ≥65 years admitted to Danish geriatric medical departments during 2005 to 2014 and included in the National Danish Geriatric Database.METHODS: Patients were followed until death, emigration, or study termination (December 31, 2015). Primary outcome was all-cause mortality. BMI and ADLs were routinely assessed on admission and linked at an individual level to the Danish national health registers. Kaplan-Meier analysis was used to estimate crude survival according to each BMI subcategory and Cox regression to examine the association with mortality adjusting for age, comorbidity, polypharmacy, ADLs, marital status, prior hospitalizations, and admission year.RESULTS: In total, 74,589 patients (63% women) were included aged [mean (SD)] 82.5 (7.5) years with BMI [mean (SD)] of 23.9 (5.1) kg/m2. During follow-up 51,188 died. Follow-up time was 191,972 person-years. Unadjusted and adjusted hazard ratio (HR) for overall, 30-day, and 1-year mortality decreased significantly with increasing BMI. In women, the highest adjusted HR (95% confidence interval) for overall mortality was seen for underweight patients (BMI CONCLUSIONS AND IMPLICATIONS: In hospitalized older patients, association between mortality and BMI did not show a U-shaped or J-shaped curve after adjustment of multiple confounders, including ADLs. Instead, mortality was highest in patients with low BMI and decreased with increasing BMI before leveling off in the obese range. Our study highlights the need for a debate and reassessment of what should be the ideal BMI in this vulnerable patient group.