Combinatorial, additive and dose-dependent drug-microbiome associations.

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

Improving student diet and food security in higher education using participatory and co-creation approaches: a systematic review.

BACKGROUND: Higher education students are an important target group for public health nutrition interventions. When designing tailored and contextually relevant interventions, participatory and co-creation approaches are increasingly recognized as promising but their use and effectiveness has not been assessed in this type of population. We systematically reviewed interventions aiming to improve dietary quality and/or food security in higher education settings with the aims 1) to identify and describe their participatory and co-creation approaches and 2) to compare the effectiveness of interventions using or not using participatory and co-creation approaches. METHODS: Our search in PubMed, Google Scholar, Web of Science, EMBASE was performed in January 2023 and yielded 3658 unique records, out of which 42 articles (66 interventions) were included. Effectiveness of interventions was assessed at the individual level (longitudinal evaluations) or at the group level (repeated cross-sectional evaluations). A five-level classification was used to describe a continuum of engagement from students and other partners in the intervention design and implementation: no participation (level one), consultation, co-production, co-design and co-creation (levels two to five). To synthetize effectiveness, comparisons were made between studies without participation (level one) or with participation (levels two-five). RESULTS: Ten (24%) out of 42 studies used a participatory and co-creation approach (levels two-five). Studies using a participatory and co-creation approach reported a positive finding on individual-level outcome (i.e. overall diet quality or food group intake or food security) in 5/13 (38%) intervention arms (vs 13/31 or 42% for those without participation). Studies using a participatory and co-creation approach reported a positive finding on group-level outcomes (i.e. food choices in campus food outlets) in 4/7 (57%) (vs 8/23 or 35% in those without participation). CONCLUSIONS: Participatory and co-creation approaches may improve the effectiveness of nutrition interventions in higher education settings but the level of evidence remains very limited. More research is warranted to identify best co-creation practices when designing, implementing and evaluating nutritional interventions in the higher education setting. TRIAL REGISTRATION: PROSPERO registration number CRD42023393004.

Cardiorespiratory fitness has declined among French children since 1999, although the decline appears to be getting smaller.

BACKGROUND: Cardiorespiratory fitness (CRF) is a strong marker of current and future health. The aim of this study was to assess the national temporal trends in CRF for French children and adolescents between 1999 and 2022. METHODS: CRF data were obtained from several cross-sectional studies on 15 420 (51.1% boys) French children and adolescents aged 9-16 years between 1999 and 2022. The 20-m shuttle run test (20mSRT) estimated CRF. Body mass index (BMI) was calculated from measured height and body mass, with BMI z-scores (BMIz) calculated using WHO growth curves. The 20mSRT results were corrected for protocol and converted to z-scores (20mSRTz) using international sex- and age-specific norms. With additional adjustment for BMIz, temporal trends in mean 20mSRT performance (20mSRTz) were estimated using linear regression, with the distance max (Dmax) method used to locate a breakpoint and linear segments fitted to points below and above the breakpoint. Trends in distributional characteristics were assessed visually and described as the ratio of the coefficients of variation (CVs). RESULTS: After adjustment for protocol, age, sex, and BMIz, a large decline in mean 20mSRT performance (trend per decade (95% CI): -1.42 SDs (-1.45, -1.39) or -18.4% (95% CI: -18.8, -18.0)) between 1999 and 2022 was found. Dmax located a breakpoint for the two-linear-segment model in year 2010. There was a large decline in mean 20mSRT performance pre-2010 (trend per decade (95% CI): -2.31 SDs (-2.39, -2.24)), which reduced 0.06-fold to a negligible decline post-2010 (trend per decade (95% CI): -0.15 SD (-0.20, -0.10)). We also found that the trend in mean 20mSRT performance was not uniform across the population distribution. Between 1999 and 2022, there was a small trend in distributional asymmetry, with slightly smaller declines experienced by the high performers (above the 75th percentile). CONCLUSIONS: Our data suggest a large decline in the 20mSRT performance of French children and adolescents since 1999. This declining trend seems to have diminished considerably since 2010. Such declines in CRF could translate into declines in health status. Although a slowing in the declining trend in CRF in recent years is encouraging, more data are needed to confirm these findings.

Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery.

BACKGROUND AND AIMS: It remains unclear to what extent and which components of advanced liver disease improve after bariatric surgery. We herein describe the histological outcome in patients with advanced NASH and its relationship with weight loss and metabolic improvement. APPROACH AND RESULTS: One hundred ninety-six patients with advanced NASH underwent bariatric surgery, 66 of whom agreed to a follow-up liver biopsy at 6 ± 3 years (36 with advanced fibrosis [AF] and 30 with high activity [HA] grade without AF). Liver biopsies LBs were centrally read and histological response was defined as the disappearance of AF or HA. Bariatric surgery induced major histological improvement: 29% of patients had normal histology at follow-up biopsy; 74% had NASH resolution without fibrosis progression; and 70% had ≥1 stage fibrosis regression. However, AF persisted in 47% of patients despite NASH resolution and some degree of fibrosis reversal, only evidenced by the EPoS seven-tier staging classification. These patients had lower weight loss and reduced hypertension or diabetes remission rates. Older age and sleeve gastrectomy were the only independent predictors for persistent AF after adjustment for duration of follow-up. All HA patients had major histological improvement: 50% normal histology, 80% NASH resolution, and 86% a ≥1 grade steatosis reduction. Patients with normal liver at follow-up had the largest weight loss and metabolic improvement. Independent predictors of normal liver were amount of weight loss, high histological activity, and the absence of AF before surgery. CONCLUSIONS: Although bariatric surgery successfully reverses active steatohepatitis, AF can persist for many years and is associated with lesser weight loss and metabolic improvement. Weight loss alone may not be sufficient to reverse AF.

Physical activity and exercise for weight loss and maintenance in people living with obesity.

Physical activity and exercise training programs are integral part of a comprehensive obesity management approach. In persons with overweight or obesity, exercise training, specifically aerobic (i.e. endurance) training, is associated with significant additional weight loss compared to the absence of training. However the magnitude of effect remains modest amounting to only 2-3 kg additional weight loss on average. Comparable effects have been observed for total fat loss. Exercise training, specifically aerobic training, is also associated with decreased abdominal visceral fat as assessed by imaging techniques, which is likely to benefit cardiometabolic health in persons with obesity. Based on data from controlled trials with randomization after prior weight loss, the evidence for weight maintenance with exercise training is as yet not conclusive, although retrospective analyses point to the value of relatively high-volume exercise in this regard. Resistance (i.e. muscle-strengthening) training is specifically advised for lean mass preservation during weight loss. Given the relatively limited effect of exercise training on weight loss as such, the changes in physical fitness brought about by exercise training cannot be overlooked as they provide major health benefits to persons with obesity. Aerobic, as well as combined aerobic and resistance training, increase cardiorespiratory fitness (VO2max) while resistance training, but not aerobic training, improves muscle strength even in the absence of a significant change in muscle mass. Regarding the overall management strategy, adherence in the long term to new lifestyle habits remains a challenging issue to be addressed by further research.

A natural experiment to assess how urban interventions in lower socioeconomic areas influence health behaviors: the UrbASanté study.

BACKGROUND: Mechanisms underlying the associations between changes in the urban environment and changes in health-related outcomes are complex and their study requires specific approaches. We describe the protocol of the interdisciplinary UrbASanté study, which aims to explore how urban interventions can modify environmental exposures (built, social, and food environments; air quality; noise), health-related behaviors, and self-reported health using a natural experiment approach. METHODS: The study is based on a natural experiment design using a before/after protocol with a control group to assess changes in environmental exposures, health-risk behaviors, and self-reported health outcomes of a resident adult population before and after the implementation of a time series of urban interventions in four contiguous neighborhoods in Paris (France). The changes in environmental exposures, health-related behaviors, and self-reported health outcomes of a resident adult population will be concurrently monitored in both intervention and control areas. We will develop a mixed-method framework combining substantial fieldwork with quantitative and qualitative analytical approaches. This study will make use of (i) data relating to exposures and health-related outcomes among all participants and in subsamples and (ii) interviews with residents regarding their perceptions of their neighborhoods and with key stakeholders regarding the urban change processing, and (iii) existing geodatabases and field observations to characterize the built, social, and food environments. The data collected will be analyzed with a focus on interrelationships between environmental exposures and health-related outcomes using appropriate approaches (e.g., interrupted time series, difference-in-differences method). DISCUSSION: Relying on a natural experiment approach, the research will provide new insights regarding issues such as close collaboration with urban/local stakeholders, recruitment and follow-up of participants, identification of control and intervention areas, timing of the planned urban interventions, and comparison of subjective and objective measurements. Through the collaborative work of a consortium ensuring complementarity between researchers from different disciplines and stakeholders, the UrbASanté study will provide evidence-based guidance for designing future urban planning and public health policies. TRIAL REGISTRATION: This research was registered at the ClinicalTrial.gov (NCT05743257).

Vertical Jump on a Force Plate for Assessing Muscle Strength and Power in Women With Severe Obesity: Reliability, Validity, and Relations With Body Composition.

ABSTRACT: Bellicha, A, Giroux, C, Ciangura, C, Menoux, D, Thoumie, P, Oppert, J-M, and Portero, P. Vertical jump on a force plate for assessing muscle strength and power in women with severe obesity: reliability, validity, and relations with body composition. J Strength Cond Res 36(1): 75-81, 2022-Muscle strength and power, particularly when assessed during multijoint movements such as vertical jump (VJ), are important predictors of health status and physical function. Vertical jump is mainly used in athletes, also in untrained or older adults, but has not yet been used in subjects with obesity. We aimed to assess the following in this population: (a) the reliability of VJ parameters, (b) their validity compared with isokinetic testing, and (c) their relations with body composition. In 20 women with severe obesity (mean [SD] age: 41.1 [11.6] years; body mass index: 43.9 [4.4] kg·m-2) without severe orthopedic disorders, VJ parameters, knee extension torque, and body composition were assessed using a force plate, an isokinetic dynamometer, and dual-energy x-ray absorptiometry, respectively. Excellent reliability was found for absolute peak power and peak force in VJ (intraclass correlation coefficient [95% confidence interval]: 0.95 [0.88-0.98] and 0.90 [0.77-0.96], respectively), and moderate to good validity of peak power and peak force compared with isokinetic torque (r = 0.79 and r = 0.67, respectively; all p < 0.01). Positive relations were found between peak force and peak power during VJ and lean body mass (r = 0.89 and r = 0.60, respectively; p < 0.01) and a negative relation was found between peak velocity or VJ height and fat mass (r = -0.65 and -0.64, respectively; p < 0.01). These results suggest that VJ on a force plate is a reliable and valid test for assessing muscle strength and power in severely obese subjects. Vertical jump testing is easy to implement, which can facilitate its use in both research and clinical testing in this setting (ClinicalTrials.govID: NCT03325764).

Neighbourhood drivability: environmental and individual characteristics associated with car use across Europe.

BACKGROUND: Car driving is a form of passive transportation associated with higher sedentary behaviour, which is associated with morbidity. The decision to drive a car is likely to be influenced by the 'drivability' of the built environment, but there is lack of scientific evidence regarding the relative contribution of environmental characteristics of car driving in Europe, compared to individual characteristics. This study aimed to determine which neighbourhood- and individual-level characteristics were associated with car driving in adults of five urban areas across Europe. Second, the study aimed to determine the percentage of variance in car driving explained by individual- and neighbourhood-level characteristics. METHODS: Neighbourhood environment characteristics potentially related to car use were identified from the literature. These characteristics were subsequently assessed using a Google Street View audit and available GIS databases, in 59 administrative residential neighbourhoods in five European urban areas. Car driving (min/week) and individual level characteristics were self-reported by study participants (analytic sample n = 4258). We used linear multilevel regression analyses to assess cross-sectional associations of individual and neighbourhood-level characteristics with weekly minutes of car driving, and assessed explained variance at each level and for the total model. RESULTS: Higher residential density (ß:-2.61, 95%CI: - 4.99; -0.22) and higher land-use mix (ß:-3.73, 95%CI: - 5.61; -1.86) were significantly associated with fewer weekly minutes of car driving. At the individual level, higher age (ß: 1.47, 95%CI: 0.60; 2.33), male sex (ß: 43.2, 95%CI:24.7; 61.7), being employed (ß:80.1, 95%CI: 53.6; 106.5) and ≥ 3 person household composition (ß: 47.4, 95%CI: 20.6; 74.2) were associated with higher weekly minutes of car driving. Individual and neighbourhood characteristics contributed about equally to explained variance in minutes of weekly car driving, with 2 and 3% respectively, but total explained variance remained low. CONCLUSIONS: Residential density and land-use mix were neighbourhood characteristics consistently associated with minutes of weekly car driving, besides age, sex, employment and household composition. Although total explained variance was low, both individual- and neighbourhood-level characteristics were similarly important in their associations with car use in five European urban areas. This study suggests that more, higher quality, and longitudinal data are needed to increase our understanding of car use and its effects on determinants of health.

Increasing physical activity in adult women with Prader-Willi syndrome: A transferability study.

BACKGROUND: The present authors aimed (a) to objectively quantify spontaneous physical activity (PA) in adult patients with Prader-Willi syndrome (PWS) and (b) to evaluate the transferability of a home-based exercise training programme in these patients. METHOD: Physical activity was compared between 10 adult women with PWS (PWS group) and 20 adult women with non-syndromic obesity (CON group, for cross-sectional comparison). In the PWS group, PA, body composition, walking capacity, quality of life and eating behaviour were then compared before and after a 16-week supervised exercise programme. RESULTS: The PWS group displayed lower PA and higher sedentary time compared to the CON group. Median attendance to exercise sessions reached 100% (Q1-Q3: 97%-100%) sessions. Moderate-to-vigorous PA and walking capacity increased after the programme without significant effect on body composition. CONCLUSION: Supervised home-based exercise sessions are an effective strategy to improve PA in women with PWS who are less active than women matched for adiposity.

Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes.

Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Spatial access to restaurants and grocery stores in relation to frequency of home cooking.

BACKGROUND: Little is known about the relation between the neighbourhood food environment and home cooking. We explored the independent and combined associations between residential neighbourhood spatial access to restaurants and grocery stores with home cooking in European adults. METHODS: Data of 5076 participants of the SPOTLIGHT study were collected across five European countries in 2014. Food retailers were classified into grocery stores (supermarkets and local food shops) and restaurants (full-service restaurants, fast food and take-away restaurants, café/bars). We used multinomial logistic regression models to test the associations between tertiles of spatial access to restaurants and spatial to access grocery stores and the outcome 'frequency of home cooking' categorized into 0-3; 4-5; and 6-7 days/week. Additive interaction analysis was used to test the combined association between access to grocery stores and to restaurants with home cooking. RESULTS: Mean age was 52.3 years; most participants were women (55.5%) and completed higher education (53.8%). Residents with highest access to restaurants had a reduced likelihood of home cooking 6-7 days/week (vs. 0-3 days/week) (relative risk ratio (RRR) 0.42; 95%CI = 0.23-0.76) when compared with lowest access to restaurants. No association was found for spatial access to grocery stores. Additive interaction analysis showed that individuals with medium access to grocery stores and highest access to restaurants had the lowest likelihood (RRR = 0.29, 95%CI = 0.10-0.84) of cooking 6-7 days/week when compared to individuals with lowest access to restaurants and highest access to grocery stores. CONCLUSION: Greater neighbourhood spatial access to restaurants was associated with lower frequency of home cooking, largely independent of access to grocery stores.

Exploring the cross-sectional association between outdoor recreational facilities and leisure-time physical activity: the role of usage and residential self-selection.

BACKGROUND: The availability of outdoor recreational facilities is associated with increased leisure-time physical activity (PA). We investigated how much of this association is attributable to selection effects, and explored whether usage of recreational facilities was an explanatory mechanism. METHODS: We analysed data from 5199 participants in the SPOTLIGHT survey residing in five European urban regions. Adults completed a survey and a Google Street View-based virtual audit was conducted to objectively measure the availability of outdoor recreational facilities in the residential neighbourhood. We used negative binomial GEE models to examine the association between objective and subjective availability of outdoor recreational facilities and leisure-time PA, and explored whether this association was attenuated after adjustment for socioeconomic status and preference for neighbourhoods with recreational facilities (as indicators of self-selection). We examined whether reported use of recreational facilities was associated with leisure-time PA (as explanatory mechanism), and summarized the most important motivations for (not) using recreational facilities. RESULTS: Subjective - but not objective - availability of outdoor recreational facilities was associated with higher levels of total leisure-time PA. After adjustment for self-selection (which attenuated the association by 25%), we found a 25% difference in weekly minutes of total leisure-time PA between individuals with and without self-reported availability of outdoor recreational facilities. For our study population, this translates to about 28 min per week. Participants who reported outdoor recreational facilities to be present but indicated not to use them (RR = 1.19, 95% CI = 1.03;1.22), and those reporting outdoor recreational facilities to be present and to use them (RR = 1.33, 95% CI = 1.22, 1.45) had higher levels of total leisure-time PA than those who reported outdoor recreational facilities not to be present. Proximity to outdoor recreational facilities was the most important motivation for use. CONCLUSION: The modest attenuation in the association between availability of outdoor recreational facilities and self-reported leisure-time PA suggests that individuals' higher activity levels may be due more to the perceived availability of outdoor recreational facilities than to self-selection. The use of these facilities seemed to be an important underlying mechanism, and proximity was the main motivator for using recreational facilities.

Lack of interest in physical activity - individual and environmental attributes in adults across Europe: The SPOTLIGHT project.

A considerable proportion of European adults report little or no interest in physical activity. Identifying individual-level and environmental-level characteristics of these individuals can help designing effective interventions and policies to promote physical activity. This cross-sectional study additionally explored associations between level of interest and physical activity, after controlling for other individual and environmental variables. Measures of objective and perceived features of the physical environment of residence, self-reported physical activity and other lifestyle behaviors, barriers towards physical activity, general health, and demographics were obtained from 5205 European adults participating in the 2014 online SPOTLIGHT survey. t-Tests, chi-square tests, and generalized estimating equations with negative binomial log-link function were conducted. Adults not interested in physical activity reported a higher BMI and a lower self-rated health, were less educated, and to a smaller extent female and less frequently employed. They were more prone to have less healthy eating habits, and to perceive more barriers towards physical activity. Only minor differences were observed in environmental attributes: the non-interested were slightly more likely to live in neighborhoods objectively characterized as less aesthetic and containing more destinations, and perceived as less functional, safe, and aesthetic. Even after controlling for other individual and environmental factors, interest in physical activity remained a significant correlate of physical activity, supporting the importance of this association. This study is among the first to describe characteristics of individuals with reduced interest in physical activity, suggesting that (lack of) interest is a robust correlate of physical activity in several personal and environmental conditions.

[Monitoring adherence after weight loss surgery: Identifying factors leading to non-adherence in a cohort of 207 severely obese patients who have undergone surgery. An evaluation of severely obese patients' adherence following weight loss surgery.] / Adhésion au suivi après chirurgie bariatrique : identification des facteurs de non observance dans une cohorte de 207 patients obèses sévères opérés. Évaluation de l'adhésion du patient obèse sévère au suivi post chirurgie bariatrique.

Obese patients are increasingly being offered weight loss surgery, the success of which depends in part on the quality of a long-term follow-up after the procedure. A study was conducted with a cohort of 207 patients operated on in 2007 and 2008 who received follow-up care in a specialized nutrition department, with the aim of identifying factors affecting their adherence to their post-operative care agenda. Factors strongly linked to a lower level of adherence were the type of surgery and a patient's place of residence. These results enable us to discuss the importance of using care coordination to optimize post-operative monitoring.

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. DESIGN: Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. RESULTS: Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). CONCLUSIONS: These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators.

The advanced-DiaRem score improves prediction of diabetes remission 1 year post-Roux-en-Y gastric bypass.

AIMS/HYPOTHESIS: Not all people with type 2 diabetes who undergo bariatric surgery achieve diabetes remission. Thus it is critical to develop methods for predicting outcomes that are applicable for clinical practice. The DiaRem score is relevant for predicting diabetes remission post-Roux-en-Y gastric bypass (RYGB), but it is not accurate for all individuals across the entire spectrum of scores. We aimed to develop an improved scoring system for predicting diabetes remission following RYGB (the Advanced-DiaRem [Ad-DiaRem]). METHODS: We used a retrospective French cohort (n = 1866) that included 352 individuals with type 2 diabetes followed for 1 year post-RYGB. We developed the Ad-DiaRem in a test cohort (n = 213) and examined its accuracy in independent cohorts from France (n = 134) and Israel (n = 99). RESULTS: Adding two clinical variables (diabetes duration and number of glucose-lowering agents) to the original DiaRem and modifying the penalties for each category led to improved predictive performance for Ad-DiaRem. Ad-DiaRem displayed improved area under the receiver operating characteristic curve and predictive accuracy compared with DiaRem (0.911 vs 0.856 and 0.841 vs 0.789, respectively; p = 0.03); thus correcting classification for 8% of those initially misclassified with DiaRem. With Ad-DiaRem, there were also fewer misclassifications of individuals with mid-range scores. This improved predictive performance was confirmed in independent cohorts. CONCLUSIONS/INTERPRETATION: We propose the Ad-DiaRem, which includes two additional clinical variables, as an optimised tool with improved accuracy to predict diabetes remission 1 year post-RYGB. This tool might be helpful for personalised management of individuals with diabetes when considering bariatric surgery in routine care, ultimately contributing to precision medicine.

Exploring the mediating role of energy balance-related behaviours in the association between sleep duration and obesity in European adults. The SPOTLIGHT project.

Sleep restriction is a risk factor for weight gain and obesity. Few studies have formally investigated the mediating role of energy balance-related behaviours in the sleep - obesity association. The aim of this study was to explore the mediating role of physical activity, sedentary behaviours and dietary habits in the association of sleep duration with obesity in adults in five European urban regions. Data on self-reported sleep duration, energy balance-related behaviours, height and weight and other covariates were collected between February and September 2014 from participants to the SPOTLIGHT survey (N=5900, mean age 52years). Participants were recruited from 60 urban neighbourhoods in Belgium, France, Hungary, the Netherlands and the United Kingdom. Multilevel logistic regression analyses were used to assess the associations of sleep duration, energy balance-related behaviours and obesity and mediating effects were calculated using MacKinnon's product-of-coefficients method. Results indicated that a 1h increase in sleeping time was associated with a 14% lower likelihood of being obese (OR=0.86, 95%CI=0.80; 0.93). Only work-related sedentary behaviour was identified as a statistically significant mediator in the association between sleep duration and obesity for the total sample, and youngest and oldest age group. We did not find evidence for a mediating role of dietary habits and physical activities.

Neighborhood educational disparities in active commuting among women: the effect of distance between the place of residence and the place of work/study (an ACTI-Cités study).

BACKGROUND: Active transportation has been associated with favorable health outcomes. Previous research highlighted the influence of neighborhood educational level on active transportation. However, little is known regarding the effect of commuting distance on social disparities in active commuting. In this regard, women have been poorly studied. The objective of this paper was to evaluate the relationship between neighborhood educational level and active commuting, and to assess whether the commuting distance modifies this relationship in adult women. METHODS: This cross-sectional study is based on a subsample of women from the Nutrinet-Santé web-cohort (N = 1169). Binomial, log-binomial and negative binomial regressions were used to assess the associations between neighborhood education level and (i) the likelihood of reporting any active commuting time, and (ii) the share of commuting time made by active transportation modes. Potential effect measure modification of distance to work on the previous associations was assessed both on the additive and the multiplicative scales. RESULTS: Neighborhood education level was positively associated with the probability of reporting any active commuting time (relative risk = 1.774; p < 0.05) and the share of commuting time spent active (relative risk = 1.423; p < 0.05). The impact of neighborhood education was greater at long distances to work for both outcomes. CONCLUSIONS: Our results suggest that neighborhood educational disparities in active commuting tend to increase with commuting distance among women. Further research is needed to provide geographically driven guidance for health promotion intervention aiming at reducing disparities in active transportation among socioeconomic groups.

The mediating role of social capital in the association between neighbourhood income inequality and body mass index.

Background: Neighbourhood income inequality may contribute to differences in body weight. We explored whether neighbourhood social capital mediated the association of neighbourhood income inequality with individual body mass index (BMI). Methods: A total of 4126 adult participants from 48 neighbourhoods in France, Hungary, the Netherlands and the UK provided information on their levels of income, perceptions of neighbourhood social capital and BMI. Factor analysis of the 13-item social capital scale revealed two social capital constructs: social networks and social cohesion. Neighbourhood income inequality was defined as the ratio of the amount of income earned by the top 20% and the bottom 20% in a given neighbourhood. Two single mediation analyses-using multilevel linear regression analyses-with neighbourhood social networks and neighbourhood social cohesion as possible mediators-were conducted using MacKinnon's product-of-coefficients method, adjusted for age, gender, education and absolute household income. Results: Higher neighbourhood income inequality was associated with elevated levels of BMI and lower levels of neighbourhood social networks and neighbourhood social cohesion. High levels of neighbourhood social networks were associated with lower BMI. Results stratified by country demonstrate that social networks fully explained the association between income inequality and BMI in France and the Netherlands. Social cohesion was only a significant mediating variable for Dutch participants. Conclusion: The results suggest that in some European urban regions, neighbourhood social capital plays a large role in the association between neighbourhood income inequality and individual BMI.