Showing papers on "Body mass index published in 2015"

Genetic studies of body mass index yield new insights for obesity biology

Abstract: Obesity is heritable and predisposes to many diseases To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals This analysis identifies 97 BMI-associated loci (P 20% of BMI variation Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis

Genetic studies of body mass index yield new insights for obesity biology

Abstract: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Abstract: BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of −5.6 kg; 95% confi dence interval, −6.0 to −5.1; P<0.001, with last-observation-carried-forward impu tation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

Modulation of genetic associations with serum urate levels by body-mass-index in humans

Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

New genetic loci link adipose and insulin biology to body fat distribution

Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

European Guidelines for Obesity Management in Adults

Abstract: Obesity is a chronic metabolic disease characterised by an increase of body fat stores. It is a gateway to ill health, and it has become one of the leading causes of disability and death, affecting not only adults but also children and adolescents worldwide. In clinical practice, the body fatness is estimated by BMI, and the accumulation of intra-abdominal fat (marker for higher metabolic and cardiovascular disease risk) can be assessed by waist circumference. Complex interactions between biological, behavioural, social and environmental factors are involved in regulation of energy balance and fat stores. A comprehensive history, physical examination and laboratory assessment relevant to the patient's obesity should be obtained. Appropriate goals of weight management emphasise realistic weight loss to achieve a reduction in health risks and should include promotion of weight loss, maintenance and prevention of weight regain. Management of co-morbidities and improving quality of life of obese patients are also included in treatment aims. Balanced hypocaloric diets result in clinically meaningful weight loss regardless of which macronutrients they emphasise. Aerobic training is the optimal mode of exercise for reducing fat mass while a programme including resistance training is needed for increasing lean mass in middle-aged and overweight/obese individuals. Cognitive behavioural therapy directly addresses behaviours that require change for successful weight loss and weight loss maintenance. Pharmacotherapy can help patients to maintain compliance and ameliorate obesity-related health risks. Surgery is the most effective treatment for morbid obesity in terms of long-term weight loss. A comprehensive obesity management can only be accomplished by a multidisciplinary obesity management team. We conclude that physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment. Treatment should be based on good clinical care, and evidence-based interventions; should focus on realistic goals and lifelong multidisciplinary management.

Body Mass Index: Obesity, BMI, and Health: A Critical Review

Abstract: The body mass index (BMI) is the metric currently in use for defining anthropometric height/weight characteristics in adults and for classifying (categorizing) them into groups. The common interpretation is that it represents an index of an individual's fatness. It also is widely used as a risk factor for the development of or the prevalence of several health issues. In addition, it is widely used in determining public health policies.The BMI has been useful in population-based studies by virtue of its wide acceptance in defining specific categories of body mass as a health issue. However, it is increasingly clear that BMI is a rather poor indicator of percent of body fat. Importantly, the BMI also does not capture information on the mass of fat in different body sites. The latter is related not only to untoward health issues but to social issues as well. Lastly, current evidence indicates there is a wide range of BMIs over which mortality risk is modest, and this is age related. All of these issues are discussed in this brief review.

Global burden of cancer attributable to high body-mass index in 2012: a population-based study

Abstract: Summary Background High body-mass index (BMI; defined as 25 kg/m 2 or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012. Methods In this population-based study, we derived population attributable fractions (PAFs) using relative risks and BMI estimates in adults by age, sex, and country. Assuming a 10-year lag-period between high BMI and cancer occurrence, we calculated PAFs using BMI estimates from 2002 and used GLOBOCAN2012 data to estimate numbers of new cancer cases attributable to high BMI. We also calculated the proportion of cancers that were potentially avoidable had populations maintained their mean BMIs recorded in 1982. We did secondary analyses to test the model and to estimate the effects of hormone replacement therapy (HRT) use and smoking. Findings Worldwide, we estimate that 481 000 or 3·6% of all new cancer cases in adults (aged 30 years and older after the 10-year lag period) in 2012 were attributable to high BMI. PAFs were greater in women than in men (5·4% vs 1·9%). The burden of attributable cases was higher in countries with very high and high human development indices (HDIs; PAF 5·3% and 4·8%, respectively) than in those with moderate (1·6%) and low HDIs (1·0%). Corpus uteri, postmenopausal breast, and colon cancers accounted for 63·6% of cancers attributable to high BMI. A quarter (about 118 000) of the cancer cases related to high BMI in 2012 could be attributed to the increase in BMI since 1982. Interpretation These findings emphasise the need for a global effort to abate the increasing numbers of people with high BMI. Assuming that the association between high BMI and cancer is causal, the continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer. Funding World Cancer Research Fund International, European Commission (Marie Curie Intra-European Fellowship), Australian National Health and Medical Research Council, and US National Institutes of Health.

Cardiometabolic Risks and Severity of Obesity in Children and Young Adults

Abstract: Background The prevalence of severe obesity among children and young adults has increased over the past decade. Although the prevalence of cardiometabolic risk factors is relatively low among children and young adults who are overweight or obese, those with more severe forms of obesity may be at greater risk. Methods We performed a cross-sectional analysis of data from overweight or obese children and young adults 3 to 19 years of age who were included in the National Health and Nutrition Examination Survey from 1999 through 2012 to assess the prevalence of multiple cardiometabolic risk factors according to the severity of obesity. Weight status was classified on the basis of measured height and weight. We used standard definitions of abnormal values for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, glycated hemoglobin, and fasting glucose and report the prevalence of abnormal values in children and young adults according to weight status. Results Among 8579 children and young adults with a body-mass index at the 85th percentile or higher (according to the Centers for Disease Control and Prevention growth charts), 46.9% were overweight, 36.4% had class I obesity, 11.9% had class II obesity, and 4.8% had class III obesity. Mean values for some, but not all, cardiometabolic variables were higher with greater severity of obesity in both male and female participants, and the values were higher in male participants than in female participants; for HDL cholesterol, the mean values were lower with greater severity of obesity. Multivariable models that controlled for age, race or ethnic group, and sex showed that the greater the severity of obesity, the higher the risks of a low HDL cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels. Conclusions Severe obesity in children and young adults was associated with an increased prevalence of cardiometabolic risk factors, particularly among boys and young men.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

Abstract: Rationale:Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host–microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. Objectives:To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. Methods and Results:We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body ...

Longitudinal impact of sleep on overweight and obesity in children and adolescents: a systematic review and bias-adjusted meta-analysis.

Abstract: Short sleep duration is considered a potential risk for overweight/obesity in childhood and adolescence. However, most of the evidence on this topic is obtained from cross-sectional studies; therefore, the nature and extent of the longitudinal associations are unclear. This study explores the prospective association between short sleep and overweight/obesity in young subjects. The MEDLINE, EMBASE, Pubmed, and CINAHL databases were searched for English-language articles, published until May 2014, reporting longitudinal association between sleep and body mass index (BMI) in children and adolescents. Recommendations of the Sleep Health Foundation were used to standardize reference sleep duration. Sleep category, with sleep duration less than the reference sleep, was considered as the short sleep category. Meta-analysis was conducted to explore the association between short sleep and overweight/obesity. A review of 22 longitudinal studies, with subjects from diverse backgrounds, suggested an inverse association between sleep duration and BMI. Meta-analysis of 11 longitudinal studies, comprising 24,821 participants, revealed that subjects sleeping for short duration had twice the risk of being overweight/obese, compared with subjects sleeping for long duration (odds ratio 2.15; 95% confidence interval: 1.64-2.81). This study provides evidence that short sleep duration in young subjects is significantly associated with future overweight/obesity.

Adiposity and cancer risk: new mechanistic insights from epidemiology

Abstract: Excess body adiposity, commonly expressed as body mass index (BMI), is a risk factor for many common adult cancers. Over the past decade, epidemiological data have shown that adiposity-cancer risk associations are specific for gender, site, geographical population, histological subtype and molecular phenotype. The biological mechanisms underpinning these associations are incompletely understood but need to take account of the specificities observed in epidemiology to better inform future prevention strategies.

Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women’s Health Initiative Randomized Clinical Trials

Abstract: Importance More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. Objective To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women’s Health Initiative (WHI) clinical trials. Design, Setting, and Participants The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67 142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed. Main Outcomes and Measures Height and weight were measured at baseline, and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history, and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators. Results Women who were overweight and obese had an increased invasive breast cancer risk vs women of normal weight. Risk was greatest for obesity grade 2 plus 3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor–positive and progesterone receptor–positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor–negative cancers. Obesity grade 2 plus 3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P = .02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P = .06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P = .05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P Conclusions and Relevance Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention. Trial Registration clinicaltrials.gov Identifier:NCT00000611

Mobile Phone Apps to Promote Weight Loss and Increase Physical Activity: A Systematic Review and Meta-Analysis

Abstract: Background: To our knowledge, no meta-analysis to date has assessed the efficacy of mobile phone apps to promote weight loss and increase physical activity. Objective: To perform a systematic review and meta-analysis of studies to compare the efficacy of mobile phone apps compared with other approaches to promote weight loss and increase physical activity. Methods: We conducted a systematic review and meta-analysis of relevant studies identified by a search of PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus from their inception through to August 2015. Two members of the study team (EG-F, GF-M) independently screened studies for inclusion criteria and extracted data. We included all controlled studies that assessed a mobile phone app intervention with weight-related health measures (ie, body weight, body mass index, or waist circumference) or physical activity outcomes. Net change estimates comparing the intervention group with the control group were pooled across studies using random-effects models. Results: We included 12 articles in this systematic review and meta-analysis. Compared with the control group, use of a mobile phone app was associated with significant changes in body weight (kg) and body mass index (kg/m 2 ) of -1.04 kg (95% CI -1.75 to -0.34; I2 = 41%) and -0.43 kg/m 2 (95% CI -0.74 to -0.13; I2 = 50%), respectively. Moreover, a nonsignificant difference in physical activity was observed between the two groups (standardized mean difference 0.40, 95% CI -0.07 to 0.87; I2 = 93%). These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. Conclusions: Evidence from this study shows that mobile phone app-based interventions may be useful tools for weight loss. [J Med Internet Res 2015;17(11):e253]

Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity

Abstract: Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring. Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother–child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode. Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33–154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8–98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS. In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

4.1 The WHO Child Growth Standards

Abstract: • Growth assessment is a key screening tool for assessing child health and nutritional wellbeing • Anthropometry is the most universally applicable, noninvasive method of assessing the growth status of children • Interpretation of the growth trajectory is highly dependent on the growth charts used • The WHO Child Growth Standards, based on the physiological growth of healthy breastfed infants, are the growth charts recommended by the WHO for universal application • Anthropometric measurements need to be accurate; adequate equipment and the use of standardized techniques are essential for reducing measurement error and minimizing bias

Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality

Abstract: Whether measures of central obesity, such as waist-to-hip ratio (WHR), provide additional information beyond body mass index (BMI) in defining mortality risks is unclear. This study examined data f...

Diagnostic performance of body mass index to identify obesity as defined by body adiposity in children and adolescents: a systematic review and meta‐analysis

Abstract: SummaryBackground The ideal means of identifying obesity in children and adolescents has not been determined although body mass index (BMI) is the most widely used screening tool Objective We performed a systematic review and meta-analysis of studies assessing the diagnostic performance of BMI to detect adiposity in children up to 18 years Methods Data sources were EMBASE, MEDLINE, Cochrane, Database of Systematic Reviews Cochrane CENTRAL, Web of Science and SCOPUS up to March 2013 Studies providing measures of diagnostic performance of BMI and using body composition technique for body fat percentage measurement were included Results Thirty-seven eligible studies that evaluated 53 521 patients, with mean age ranging from 4 to 18 years were included in the meta-analysis Commonly used BMI cut-offs for obesity showed pooled sensitivity to detect high adiposity of 073 (confidence interval [CI] 067–079), specificity of 093 (CI 088–096) and diagnostic odds ratio of 3693 (CI 2075–6571) Males had lower sensitivity Moderate heterogeneity was observed (I2 = 48%) explained in meta-regression by differences across studies in race, BMI cut-off, BMI reference criteria (Center for Disease Control vs International Obesity Task Force) and reference standard method assessing adiposity Conclusion BMI has high specificity but low sensitivity to detect excess adiposity and fails to identify over a quarter of children with excess body fat percentage

The airway microbiome in patients with severe asthma: Associations with disease features and severity

Abstract: Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma Whether similar relationships exist among patients with severe asthma is unknown Objective We sought to evaluate relationships between the bronchial microbiome and features of severe asthma Methods Bronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA–based methods Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41) Results In patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index ( P P P = 06), and bronchial biopsy eosinophil values (per square millimeter, P = 07) Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes) In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5) , an indicator of steroid responsiveness, correlated with Actinobacteria Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria No taxa were associated with a T H 2-related epithelial gene expression signature, but expression of T H 17-related genes was associated with Proteobacteria Patients with severe asthma compared with healthy control subjects or patients with mild-to-moderate asthma were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (78-fold increase in patients with severe asthma, adjusted P Conclusions Specific microbiota are associated with and may modulate inflammatory processes in patients with severe asthma and related phenotypes Airway dysbiosis in patients with severe asthma appears to differ from that observed in those with milder asthma in the setting of inhaled corticosteroid use

Social jetlag, obesity and metabolic disorder: investigation in a cohort study.

Abstract: Background: Obesity is one of the leading causes of preventable death worldwide. Circadian rhythms are known to control both sleep timing and energy homeostasis, and disruptions in circadian rhythms have been linked with metabolic dysfunction and obesity-associated disease. In previous research, social jetlag, a measure of chronic circadian disruption caused by the discrepancy between our internal versus social clocks, was associated with elevated self-reported body mass index, possibly indicative of a more generalized association with obesity and metabolic dysfunction. Methods: We studied participants from the population-representative Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was associated with clinically assessed measurements of metabolic phenotypes and disease indicators for obesity-related disease, specifically, indicators of inflammation and diabetes. Results: Our analysis was restricted to N=815 non-shift workers in our cohort. Among these participants, we found that social jetlag was associated with numerous clinically assessed measures of metabolic dysfunction and obesity. We distinguished between obese individuals who were metabolically healthy versus unhealthy, and found higher social jetlag levels in metabolically unhealthy obese individuals. Among metabolically unhealthy obese individuals, social jetlag was additionally associated with elevated glycated hemoglobin and an indicator of inflammation. Conclusions: The findings are consistent with the possibility that ‘living against our internal clock’ may contribute to metabolic dysfunction and its consequences. Further research aimed at understanding that the physiology and social features of social jetlag may inform obesity prevention and have ramifications for policies and practices that contribute to increased social jetlag, such as work schedules and daylight savings time.

Meta-Analysis of the Relation of Body Mass Index to All-Cause and Cardiovascular Mortality and Hospitalization in Patients With Chronic Heart Failure

Abstract: Clinical studies have indicated the existence of an "obesity paradox" in patients with chronic heart failure (HF), that is, reduced mortality in patients who have elevated body mass index (BMI) scores compared with normal-weight reference groups. The aim of this study was to investigate the relation of BMI with all-cause and cardiovascular (CV) mortality and hospitalization in patients with chronic HF though a systematic review and meta-analysis of published research. PubMed, the Cumulative Index to Nursing and Allied Health Literature, Cochrane Central, Scopus, web of science and Embase were searched for studies reporting rates of total mortality, cardiac mortality, and risk for hospitalization in patients with HF in various BMI categories (<20 kg/m(2) [low], 20 to 24.9 kg/m(2) [normal reference], 25 to 29.9 kg/m(2) [overweight], 30 to 34.9 [obese], and ≥35 kg/m(2) [severely obese]). Event rates were compared using a forest plot of relative risk (RR) using a random-effects model assuming interstudy heterogeneity. Two study investigators independently reviewed the 124 reports retrieved and identified 6 for final analyses (n = 22,807). After a mean follow-up period of 2.85 years, the risk for adverse events was highest in patients with low BMIs: total mortality RR 1.27 (95% confidence interval [CI] 1.17 to 1.37), CV mortality RR 1.20 (95% CI 1.01 to 1.43), and hospitalization RR 1.19 (95% CI 1.09 to 1.30). Risk for CV mortality and hospitalization was lowest in overweight patients (RR 0.79, 95% CI 0.70 to 0.90, and RR 0.92, 95% CI 0.86 to 0.97, respectively). Increasing degree of obesity failed to achieve a statistically significant effect on CV mortality (RR 0.82, 95% CI 0.64 to 1.05, and RR 0.71, 95% CI 0.50 to 1.01, for obese and severely obese, respectively) and on hospitalization (RR 0.99, 95% CI 0.92 to 1.07, and RR 1.28, 95% CI 0.88 to 1.87, for obese and severely obese, respectively). In conclusion, risk for total mortality and CV mortality and hospitalization was highest in patients with chronic HF who were underweight as defined by low BMI, whereas risk for CV mortality and hospitalization was lowest in overweight subjects.

The Effect of Lifestyle Intervention and Metformin on Preventing or Delaying Diabetes Among Women With and Without Gestational Diabetes: The Diabetes Prevention Program Outcomes Study 10-Year Follow-Up

Abstract: Context: Gestational diabetes (GDM) confers a high risk of type 2 diabetes In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM Objective: The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study Design: This was a randomized controlled clinical trial with an observational follow-up Setting: The study was conducted at 27 clinical centers Participants: Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry Interventions: Interventions included placebo, ILS, or metformin Outcomes Measure: Outcomes measure was diabetes mellitus Results: Over 10 years, women with a history of GDM

Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies

Abstract: Backgrounds: Considerable evidence suggests that adiposity, measured by body mass index, is implicated in carcinogenesis. While adult weigh gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain and risks of major cancers are lacking. Methods: PubMed and Embase were searched from the inception to May, 2014 to identify prospective observational studies investigating the relationship between adult weight gain and incident cancers of the breast, prostate, and colorectum. Dose-response meta-analyses were performed using a random-effects model to estimate summary relative risk (RR) and 95% confidence interval (CI) for each cancer type. Results: In the linear dose-response estimating cancer risk associated with 5kg increase in adult weight gain, a statistically significant direct association was found only for postmenopausal breast cancer and colon cancer. The summary RR was 1.11 (95% CI=1.08-1.13, I2=22%, seven studies with 4,570 cases, range=0-35kg) for postmenopausal breast cancer; 0.99 (95% CI=0.95-1.03, I2=36%, three studies with 2,409 cases, range=0-27.5kg) for premenopausal breast cancer. Etiologic heterogeneity by menopausal status at diagnosis was statistically significant (Pheterogeneity=0.001). The summary RR for colon cancer was 1.06 (95% CI=1.03-1.10, I2=0%, four studies with 2,909 cases, range=0-29kg). While there was no evidence of heterogeneity by sex (Pheterogeneity=0.17), the association was statistically significant only among men. No evidence of a linear association was indicated for prostate cancer (RR=0.98, 95% CI=0.94-1.02, four studies with 6,882 cases, range=0-25kg) and for its subtypes (localized: RR=0.96, 95% CI=0.92-1.00, I2=38%; advanced: RR=1.04, 95% CI=0.99-1.09, I2=0%). Conclusions: Avoiding adult weight gain itself may confer protection against postmenopausal breast cancer and colon cancer. As preventing weight gain is relatively more feasible than losing weight, clinicians and public health policies may prioritize weight maintenance throughout adulthood to reduce the burden of postmenopausal breast cancer and colon cancer.

The use of measures of obesity in childhood for predicting obesity and the development of obesity-related diseases in adulthood: a systematic review and meta-analysis.

Abstract: BACKGROUND: It is uncertain which simple measures of childhood obesity are best for predicting future obesity-related health problems and the persistence of obesity into adolescence and adulthood OBJECTIVES: To investigate the ability of simple measures, such as body mass index (BMI), to predict the persistence of obesity from childhood into adulthood and to predict obesity-related adult morbidities To investigate how accurately simple measures diagnose obesity in children, and how acceptable these measures are to children, carers and health professionals DATA SOURCES: Multiple sources including MEDLINE, EMBASE and The Cochrane Library were searched from 2008 to 2013 METHODS: Systematic reviews and a meta-analysis were carried out of large cohort studies on the association between childhood obesity and adult obesity; the association between childhood obesity and obesity-related morbidities in adulthood; and the diagnostic accuracy of simple childhood obesity measures Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and a modified version of the Quality in Prognosis Studies (QUIPS) tool A systematic review and an elicitation exercise were conducted on the acceptability of the simple measures RESULTS: Thirty-seven studies (22 cohorts) were included in the review of prediction of adult morbidities Twenty-three studies (16 cohorts) were included in the tracking review All studies included BMI There were very few studies of other measures There was a strong positive association between high childhood BMI and adult obesity [odds ratio 521, 95% confidence interval (CI) 450 to 602] A positive association was found between high childhood BMI and adult coronary heart disease, diabetes and a range of cancers, but not stroke or breast cancer The predictive accuracy of childhood BMI to predict any adult morbidity was very low, with most morbidities occurring in adults who were of healthy weight in childhood Predictive accuracy of childhood obesity was moderate for predicting adult obesity, with a sensitivity of 30% and a specificity of 98% Persistence of obesity from adolescence to adulthood was high Thirty-four studies were included in the diagnostic accuracy review Most of the studies used the least reliable reference standard (dual-energy X-ray absorptiometry); only 24% of studies were of high quality The sensitivity of BMI for diagnosing obesity and overweight varied considerably; specificity was less variable Pooled sensitivity of BMI was 74% (95% CI 642% to 818%) and pooled specificity was 95% (95% CI 922% to 964%) The acceptability to children and their carers of BMI or other common simple measures was generally good LIMITATIONS: Little evidence was available regarding childhood measures other than BMI No individual-level analysis could be performed CONCLUSIONS: Childhood BMI is not a good predictor of adult obesity or adult disease; the majority of obese adults were not obese as children and most obesity-related adult morbidity occurs in adults who had a healthy childhood weight However, obesity (as measured using BMI) was found to persist from childhood to adulthood, with most obese adolescents also being obese in adulthood BMI was found to be reasonably good for diagnosing obesity during childhood There is no convincing evidence suggesting that any simple measure is better than BMI for diagnosing obesity in childhood or predicting adult obesity and morbidity Further research on obesity measures other than BMI is needed to determine which is the best tool for diagnosing childhood obesity, and new cohort studies are needed to investigate the impact of contemporary childhood obesity on adult obesity and obesity-related morbidities STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005711 FUNDING: The National Institute for Health Research Health Technology Assessment programme

Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study.

Abstract: Aim The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favourable metabolic profile. Its prognostic value is unclear and may depend on the health outcome being examined. We examined the association of MHO phenotype with incident cardiovascular disease (CVD) and type 2 diabetes. Methods and results Body mass index and metabolic health, assessed using the Adult Treatment Panel-III (ATP-III) criteria, were assessed on 7122 participants (69.7% men) from the Whitehall II study, aged 39–63 years in 1991–93. Incident CVD (coronary heart disease or stroke) and type 2 diabetes were ascertained from medical screenings (every 5 years), hospital data, and registry linkage until 2009. A total of 657 individuals (9.2% of the cohort) were obese and 42.5% of these were classified as MHO in 1991–93. Over the median follow-up of 17.4 years, there were 828 incident cases of CVD and 798 incident cases of type 2 diabetes. Compared with metabolically healthy normal weight individuals, MHO subjects were at increased risk for CVD (HR = 1.97, 95% CI: 1.38–2.80) and type 2 diabetes (3.25, 95% CI: 2.32–4.54). There was excess risk in metabolically unhealthy obese compared with MHO for type 2 diabetes (1.98, 95% CI: 1.39–2.83) but not CVD (1.23, 95% CI: 0.81–1.87). Treating all measures as time varying covariates produced similar findings. Conclusion For type 2 diabetes, the MHO phenotype is associated with lower risk than the metabolically unhealthy obese, but for CVD the risk is as elevated in both obesity phenotypes.

Probability of an obese person attaining normal body weight: Cohort study using electronic health records

Abstract: Objectives: Obesity is an increasing clinical and public health concern. This study aimed to answer the question: ‘What is the probability of an obese person attaining normal body weight?’ Methods: A sample of men and women aged 20 years and over was drawn from the Clinical Practice Research Datalink (CPRD). Participants who received bariatric surgery were excluded. The probability of attaining either normal weight, or 5% reduction in body weight, were estimated. Findings: Data were analysed for 278,982 participants including 76,704 obese men and 99,791 obese women. During a maximum of 9 years’ follow-up, 1,283 men and 2,245 women attained normal body weight. In simple obesity (BMI 30•0-34•9 Kg/m2), the annual probability of attaining normal weight was 1 in 210 for men and 1 in 124 for women, increasing to 1 in 1,290 for men and 1 in 677 for women with morbid obesity (BMI 40•0-44•9 Kg/m2). The annual probability of achieving a 5% weight reduction was 1 in 8 for men, and 1 in 7 for women with morbid obesity. Among participants who lost 5% body weight, 52•7% (95% confidence interval 52•4 to 53•0%) showed weight regain at two years and 78•0% (77•7 to 78•3%) at five years. Conclusions: The low probability of attaining normal weight, or maintaining weight loss, raises questions concerning whether current obesity treatment frameworks, grounded in community-based weight management programmes, may be expected to achieve public health impact.