The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids.

Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.

Long-lasting effects of the COVID-19 pandemic on lifestyle and body weight: results of representative cross-sectional surveys in adults in Germany.

BACKGROUND: The COVID-19 pandemic severely affected people's daily lives and health. Few studies have looked into the persistence of these changes. In the current study, we investigated to what extent changes in lifestyle and body weight were sustained after two years of restrictions. METHODS: We performed two representative online surveys among adults living in Germany. The first survey (S1) was performed in April 2021; the second survey (S2) in June 2022. The questionnaire focused on changes in physical activity, dietary habits, body weight, and mental stress levels. The data were weighted to optimally represent the general population of Germany. Using Chi-square tests, results were compared between the two surveys, and - per survey - between subgroups based on sociodemographic factors and mental stress levels. Furthermore, binomial logistic regression was performed to identify factors associated with weight gain. RESULTS: A total of 1,001 (S1) and 1,005 (S2) adults completed the survey, of which 50.4% were men and 49.6% were women in both surveys. Mean body mass index (BMI) at the time of the survey was 27.4 ± 6.0 kg/m2 (S1) and 27.1 ± 5.5 kg/m2 (S2). Reduced physical activity was reported by 52% of the participants in S1 and by 40% in S2 (p < .001). Moderate to severe stress was reported by 71% of the participants in S1 and by 62% in S2 (p < .001). Less healthy eating compared to before the pandemic was reported by 16% of the participants in S1 and by 12% in S2 (p = 0.033). Weight gain was reported by 40% of the participants in S1 and by 35% in S2 (p = 0.059). Weight gain was associated with higher BMI, reduced physical activity levels, less healthy nutrition and increased consumption of energy-dense food. CONCLUSIONS: Our results indicate that two years and three months after the start of the COVID-19 pandemic, the adverse effects on health-related lifestyle factors and body weight still existed, albeit to a lesser degree than directly after the first year of the pandemic. Targeted strategies are needed to better support the population subgroups most likely to change their lifestyle in unfavorable ways when faced with disruptions of their everyday lives.

Characterization of adults concerning the use of a hypothetical mHealth application addressing stress-overeating: an online survey.

BACKGROUND: About 40% of people respond to stress by consuming more unhealthy foods. This behavior is associated with increased energy intake and the risk of obesity. As mobile health (mHealth) applications (apps) have been shown to be an easy-to-use intervention tool, the characterization of potential app users is necessary to develop target group-specific apps and to increase adherence rates. METHODS: This cross-sectional online survey was conducted in the spring of 2021 in Germany. Sociodemographic data and data on personality (Big Five Inventory, BFI-10), stress-eating (Salzburg Stress Eating Scale, SSES), and technology behavior (Personal Innovativeness in the Domain of Information Technology, PIIT; Technology Acceptance Model 3, TAM 3) were collected. RESULTS: The analysis included 1228 participants (80.6% female, mean age: 31.4 ± 12.8 years, mean body mass index (BMI): 23.4 ± 4.3 kg/m2). Based on the TAM score, 33.3% (409/1228) of the participants had a high intention to use a hypothetical mHealth app to avoid stress-overeating. These persons are characterized by a higher BMI (24.02 ± 4.47 kg/m2, p < 0.001), by being stress-overeaters (217/409, 53.1%), by the personality trait "neuroticism" (p < 0.001), by having specific eating reasons (all p < 0.01), and by showing a higher willingness to adopt new technologies (p < 0.001). CONCLUSION: This study suggests that individuals who are prone to stress-overeating are highly interested in adopting an mHealth app as support. Participants with a high intention to use an mHealth app seem to have a general affinity towards new technology (PIIT) and appear to be more insecure with conflicting motives regarding their diet. TRIAL REGISTRATION: This survey was registered in the German Clinical Trials Register (Registration number: DRKS00023984).

How does gestational weight gain influence short- and long-term postpartum weight retention? An updated systematic review and meta-analysis.

This systematic review and meta-analysis provide an update of an earlier meta-analysis examining the impact of gestational weight gain (GWG) on postpartum weight retention (PPWR). Thirty-four observational studies were included, and results from 18 studies were combined in meta-analyses. We found that women with excessive GWG retained an additional 2.98 kg (95% CI: 0.59, 5.37 kg, I2  = 91%) at 0.5 years, 1.89 kg (95% CI: 0.90, 2.88 kg, I2  = 61%) at > 0.5-1 year and 2.89 kg (95% CI: 1.74, 4.04 kg, I 2  = 0%) at 2-4 years, compared to women who met the National Academy of Medicine GWG recommendations. Moreover, synthesis of confounder-adjusted regression coefficients showed that each 1 kg increase of GWG corresponded to 0.62 kg (95% CI: 0.22, 1.02 kg, I2  = 96%) additional PPWR at 6-9 months, 0.48 kg (95% CI: 0.14, 0.81 kg, I2  = 93%) at 1-3 years, and 0.31 kg (95% CI: -0.24, 0.86 kg, I2  = 89%) at 5-7 years postpartum. Findings suggest that higher GWG contributes to increased maternal body weight in the short- and long-term after childbirth, independent of prepregnancy body mass index. The heterogeneity of reported data and methodological differences across studies complicate the ability to synthesize data and interpret findings.

Efficacy of an app-based multimodal lifestyle intervention on body weight in persons with obesity: results from a randomized controlled trial.

BACKGROUND: Despite an increasing number of smartphone applications (apps) addressing weight management, data on the effect of app-based multimodal obesity treatment approaches on weight loss is limited. This study aimed to examine the effect of a digital multimodal weight loss intervention program delivered by an app on body weight in persons with obesity. METHODS: For this single-centre randomized controlled study, 168 adults with a body mass index (BMI) between 30.0 and 40.0 kg/m2 without severe comorbidities were recruited in the region of Munich and randomized into two intervention groups. The ADHOC group received an app-based multimodal weight loss program from baseline on for 12 weeks plus 12 weeks of follow-up. The EXPECT group received the app-based intervention for 12 weeks after 12 weeks of "waiting" (no intervention). Anthropometric data, data on quality of life (EuroQol, EQ-5D-5L), and app usage data were collected. RESULTS: 64.3% of study participants were women, mean age was 46.8 ± 11.0 years, and mean BMI was 34.2 ± 2.8 kg/m2. The completers analysis resulted in a weight loss of 3.2 ± 3.2 kg (3.2 ± 3.0%) in the ADHOC group and 0.4 ± 2.6 kg (0.3 ± 2.6%) in the EXPECT group after 12 weeks, with a significant difference between the groups (ß [95% CI] = -2.9 [-3.8; -1.9], p < 0.001). Completers in the ADHOC group showed weight maintenance after 24 weeks. The time spent on the app was associated with weight reduction (ß [95% CI] = -0.10 [-0.18; -0.01], p = 0.03). CONCLUSIONS: Application of a multimodal app-based weight loss program results in moderate weight loss in persons with obesity. TRIAL REGISTRATION: This study was registered in the German Clinical Trials Register (Registration number: DRKS00025291).

Analysis of type 2 diabetes heterogeneity with a tree-like representation: insights from the prospective German Diabetes Study and the LURIC cohort.

BACKGROUND: Heterogeneity in type 2 diabetes can be represented by a tree-like graph structure by use of reversed graph-embedded dimensionality reduction. We aimed to examine whether this approach can be used to stratify key pathophysiological components and diabetes-related complications during longitudinal follow-up of individuals with recent-onset type 2 diabetes. METHODS: For this cohort analysis, 927 participants aged 18-69 years from the German Diabetes Study (GDS) with recent-onset type 2 diabetes were mapped onto a previously developed two-dimensional tree based on nine simple clinical and laboratory variables, residualised for age and sex. Insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, insulin secretion was assessed by intravenous glucose tolerance test, hepatic lipid content was assessed by 1 H magnetic resonance spectroscopy, serum interleukin (IL)-6 and IL-18 were assessed by ELISA, and peripheral and autonomic neuropathy were assessed by functional and clinical measures. Participants were followed up for up to 16 years. We also investigated heart failure and all-cause mortality in 794 individuals with type 2 diabetes undergoing invasive coronary diagnostics from the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort. FINDINGS: There were gradients of clamp-measured insulin sensitivity (both dimensions: p<0·0001) and insulin secretion (pdim1<0·0001, pdim2=0·00097) across the tree. Individuals in the region with the lowest insulin sensitivity had the highest hepatic lipid content (n=205, pdim1<0·0001, pdim2=0·037), pro-inflammatory biomarkers (IL-6: n=348, pdim1<0·0001, pdim2=0·013; IL-18: n=350, pdim1<0·0001, pdim2=0·38), and elevated cardiovascular risk (nevents=143, pdim1=0·14, pdim2<0·00081), whereas individuals positioned in the branch with the lowest insulin secretion were more prone to require insulin therapy (nevents=85, pdim1=0·032, pdim2=0·12) and had the highest risk of diabetic sensorimotor polyneuropathy (nevents=184, pdim1=0·012, pdim2=0·044) and cardiac autonomic neuropathy (nevents=118, pdim1=0·0094, pdim2=0·06). In the LURIC cohort, all-cause mortality was highest in the tree branch showing insulin resistance (nevents=488, pdim1=0·12, pdim2=0·0032). Significant gradients differentiated individuals having heart failure with preserved ejection fraction from those who had heart failure with reduced ejection fraction. INTERPRETATION: These data define the pathophysiological underpinnings of the tree structure, which has the potential to stratify diabetes-related complications on the basis of routinely available variables and thereby expand the toolbox of precision diabetes diagnosis. FUNDING: German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, European Community, German Research Foundation, and Schmutzler Stiftung.

App-Supported Lifestyle Interventions in Pregnancy to Manage Gestational Weight Gain and Prevent Gestational Diabetes: Scoping Review.

BACKGROUND: Excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM) are common pregnancy complications that have been shown to be preventable through the use of lifestyle interventions. However, a significant gap exists between research on pregnancy lifestyle interventions and translation into clinical practice. App-supported interventions might aid in overcoming previous implementation barriers. The current status in this emerging research area is unknown. OBJECTIVE: This scoping review aims to provide a comprehensive overview of planned, ongoing, and completed studies on eHealth and mobile health (mHealth) app-supported lifestyle interventions in pregnancy to manage GWG and prevent GDM. The review assesses the scope of the literature in the field; describes the population, intervention, control, outcomes, and study design (PICOS) characteristics of included studies as well as the findings on GWG and GDM outcomes; and examines app functionalities. METHODS: The scoping review was conducted according to a preregistered protocol and followed established frameworks. Four electronic databases and 2 clinical trial registers were systematically searched. All randomized and quasi-randomized controlled trials (RCTs) of app-supported lifestyle interventions in pregnancy and related qualitative and quantitative research across the different study phases were considered for inclusion. Eligible studies and reports of studies were included until June 2022. Extracted data were compiled in descriptive analyses and reported in narrative, tabular, and graphical formats. RESULTS: This review included 97 reports from 43 lifestyle intervention studies. The number of published reports has steadily increased in recent years; of the 97 included reports, 38 (39%) were trial register entries. Of the 39 identified RCTs, 10 efficacy or effectiveness trials and 8 pilot trials had published results on GWG (18/39, 46%); of these 18 trials, 7 (39%) trials observed significant intervention effects on GWG outcomes. Of all 39 RCTs, 5 (13%) efficacy or effectiveness trials reported GDM results, but none observed significant intervention effects on GDM. The RCTs included in the review were heterogeneous in terms of their PICOS characteristics. Most of the RCTs were conducted in high-income countries, included women with overweight or obesity and from all BMI categories, delivered multicomponent interventions, delivered interventions during pregnancy only, and focused on diet and physical activity. The apps used in the studies were mostly mHealth apps that included features for self-monitoring, feedback, goal setting, prompts, and educational content. Self-monitoring was often supported by wearable activity monitors and Bluetooth-connected weight scales. CONCLUSIONS: Research in this field is nascent, and the effectiveness and implementability of app-supported interventions have yet to be determined. The complexity and heterogeneity of intervention approaches pose challenges in identifying the most beneficial app features and intervention components and call for consistent and comprehensive intervention and outcome reporting.

Benefits of Fiber-Enriched Foods on Satiety and Parameters of Human Well-Being in Adults with and without Cardiometabolic Risk.

Consumption of fiber-rich foods is linked to beneficial effects on chronic diseases and gut health, while implications towards improving satiety and parameters of well-being remain unclear. A randomized placebo-controlled intervention study was conducted to compare the effects of fiber-enriched foods to their non-enriched counterparts in adults over a 12-week period on selected clinical parameters-satiety, quality of life, body sensation, and life satisfaction-subjective health status, and importance of diet for well-being. Quality of life (QOL) differed significantly between intervention and control groups at baseline, throughout, and at the end of the study. No effects on satiety, satisfaction with life, or the importance of diet for well-being could be shown between groups. With higher fiber intake, body sensation ratings increased. A higher BMI was significantly associated with lower-body sensation, subjective health status and quality of life. Fiber-enriched foods do not seem to affect feeling of satiety or parameters of well-being. Larger samples and additional methods are necessary to fully explore the effect of increased fiber intake on patient-related outcomes in more detail.

Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS).

BACKGROUND: Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes. METHODS: In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS) was assessed, and the results were validated against participants from the Diabetes Prevention Program (DPP) study. For PLIS, between March 1, 2012, and Aug 31, 2016, participants were recruited from eight clinical study centres (including seven university hospitals) in Germany and randomly assigned to receive either a control intervention, a standard lifestyle intervention (ie, DPP-based intervention), or an intensified lifestyle intervention for 12 months. For DPP, participants were recruited from 23 clinical study centres in the USA between July 31, 1996, and May 18, 1999, and randomly assigned to receive either a standard lifestyle intervention, metformin, or placebo. In both PLIS and DPP, only participants who were randomly assigned to receive lifestyle intervention or placebo and who lost at least 5% of their bodyweight were included in this analysis. Responders were defined as people who returned to normal fasting plasma glucose (FPG; <5·6 mmol/L), normal glucose tolerance (<7·8 mmol/L), and HbA1c less than 39 mmol/mol after 12 months of lifestyle intervention or placebo or control intervention. Non-responders were defined as people who had FPG, 2 h glucose, or HbA1c more than these thresholds. The main outcomes for this analysis were insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL) and were evaluated via linear mixed models. FINDINGS: Of 1160 participants recruited to PLIS, 298 (25·7%) had weight loss of 5% or more of their bodyweight at baseline. 128 (43%) of 298 participants were responders and 170 (57%) were non-responders. Responders were younger than non-responders (mean age 55·6 years [SD 9·9] vs 60·4 years [8·6]; p<0·0001). The DPP validation cohort included 683 participants who lost at least 5% of their bodyweight at baseline. Of these, 132 (19%) were responders and 551 (81%) were non-responders. In PLIS, BMI reduction was similar between responders and non-responders (responders mean at baseline 32·4 kg/m2 [SD 5·6] to mean at 12 months 29·0 kg/m2 [4·9] vs non-responders 32·1 kg/m2 [5·9] to 29·2 kg/m2 [5·4]; p=0·86). However, whole-body insulin sensitivity increased more in responders than in non-responders (mean at baseline 291 mL/[min × m2], SD 60 to mean at 12 months 378 mL/[min × m2], 56 vs 278 mL/[min × m2], 62, to 323 mL/[min × m2], 66; p<0·0001), whereas insulin secretion did not differ within groups over time or between groups (responders mean at baseline 175 pmol/mmol [SD 64] to mean at 12 months 163·7 pmol/mmol [60·6] vs non-responders 158·0 pmol/mmol [55·6] to 154·1 pmol/mmol [56·2]; p=0·46). IHL decreased in both groups, without a difference between groups (responders mean at baseline 10·1% [SD 8·7] to mean at 12 months 3·5% [3·9] vs non-responders 10·3% [8·1] to 4·2% [4·2]; p=0·34); however, VAT decreased more in responders than in non-responders (mean at baseline 6·2 L [SD 2·9] to mean at 12 months 4·1 L [2·3] vs 5·7 L [2·3] to 4·5 L [2·2]; p=0·0003). Responders had a 73% lower risk of developing type 2 diabetes than non-responders in the 2 years after the intervention ended. INTERPRETATION: By contrast to remission of type 2 diabetes, resolution of prediabetes was characterised by an improvement in insulin sensitivity and reduced VAT. Because return to normal glucose regulation (NGR) prevents development of type 2 diabetes, we propose the concept of remission of prediabetes in analogy to type 2 diabetes. We suggest that remission of prediabetes should be the primary therapeutic aim in individuals with prediabetes. FUNDING: German Federal Ministry for Education and Research via the German Center for Diabetes Research; the Ministry of Science, Research and the Arts Baden-Württemberg; the Helmholtz Association and Helmholtz Munich; the Cluster of Excellence Controlling Microbes to Fight Infections; and the German Research Foundation.

The HuMet Repository: Watching human metabolism at work.

The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in health and disease, detailed documentation of healthy metabolic responses is needed but still scarce on a time-resolved metabolome-wide level. Here, we present the HuMet Repository, a web-based resource for exploring dynamic metabolic responses to six physiological challenges (exercise, 36 h fasting, oral glucose and lipid loads, mixed meal, cold stress) in healthy subjects. For building this resource, we integrated existing and newly derived metabolomics data measured in blood, urine, and breath samples of 15 young healthy men at up to 56 time points during the six highly standardized challenge tests conducted over four days. The data comprise 1.1 million data points acquired on multiple platforms with temporal profiles of 2,656 metabolites from a broad range of biochemical pathways. By embedding the dataset into an interactive web application, we enable users to easily access, search, filter, analyze, and visualize the time-resolved metabolomic readouts and derived results. Users can put metabolites into their larger context by identifying metabolites with similar trajectories or by visualizing metabolites within holistic metabolic networks to pinpoint pathways of interest. In three showcases, we outline the value of the repository for gaining biological insights and generating hypotheses by analyzing the wash-out of dietary markers, the complementarity of metabolomics platforms in dynamic versus cross-sectional data, and similarities and differences in systemic metabolic responses across challenges. With its comprehensive collection of time-resolved metabolomics data, the HuMet Repository, freely accessible at https://humet.org/, is a reference for normal, healthy responses to metabolic challenges in young males. It will enable researchers with and without computational expertise, to flexibly query the data for their own research into the dynamics of human metabolism.

Antibiotic Treatment During Pregnancy and the First Six Months Postpartum - a Secondary Analysis of the "Healthy Living in Pregnancy" (GeliS) Study.

Introduction: Antibiotic therapies for the treatment of bacterial infections pose a particular challenge during pregnancy and breastfeeding. For Germany, there is hardly any information on the frequency of antibiotic use during this phase. Our analysis uses data from the "Healthy Living in Pregnancy" (GeliS) study to describe antibiotic treatments during pregnancy and in the first six months after birth (postpartum), and to compare their use with existing recommendations. Methods: This is a retrospective secondary analysis of the GeliS study. In the cluster randomized lifestyle intervention study, detailed information on antibiotic therapies during pregnancy and postpartum was collected using surveys. Chi-square tests and generalized estimating equations were used for evaluation. Results: Of the 1636 women included in the analysis, 21% reported antibiotic treatment at least once during pregnancy (14%) or in the first six months postpartum (7%). During pregnancy, the antibiotic therapies of women increased from 1.7% in the first trimester to 6.5% in the third trimester. Common reasons for treatment were urinary tract infections (7.3% of women), ear, nose, throat (ENT) infections (3.6%), and birth complications (2.6%). The information on the prescribed preparations corresponded to the current recommendations. A significant increase in the frequency of treatment with antibiotics was observed in the lifestyle intervention group (p < 0.001), in participants without a partner (p < 0.001), and in women who breastfed their children (p = 0.005) or gave birth by caesarean section (p = 0.003) or prematurely (p = 0.012). Other socioeconomic or lifestyle factors were not significant. Conclusion: Approximately one in five women receives at least one antibiotic treatment during pregnancy and breastfeeding that meets current treatment recommendations. Treatment with antibiotics is more common in premature births, caesarean sections, and breastfeeding women.

Global Alliance for the Promotion of Physical Activity: the Hamburg Declaration.

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.

Fusobacterium sphaericum sp. nov. , isolated from a human colon tumor, is prevalent in various human body sites and induces IL-8 secretion from colorectal cancer cells.

Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. ( Fs ), isolated from primary colon adenocarcinoma tissue. We acquire the complete, closed genome of this organism and phylogenetically confirm its classification into the Fusobacterium genus. Phenotypic and genomic analysis of Fs reveal that this novel organism is of coccoid shape, rare for Fusobacterium members, and has species-distinct gene content. Fs displays a metabolic profile and antibiotic resistance repertoire consistent with other Fusobacterium species. In vitro, Fs has adherent and immunomodulatory capabilities, as it intimately associates with human colon cancer epithelial cells and promotes IL-8 secretion. Analysis of the prevalence and abundance of Fs in ∼1,750 human metagenomic samples shows that it is a moderately prevalent member of the human oral cavity and stool. Intriguingly, analysis of ∼1,270 specimens from patients with colorectal cancer demonstrate that Fs is significantly enriched in colonic and tumor tissue as compared to mucosa or feces. Our study sheds light on a novel bacterial species that is prevalent within the human intestinal microbiota and whose role in human health and disease requires further investigation.

Automated segmentation of the human supraclavicular fat depot via deep neural network in water-fat separated magnetic resonance images.

Background: Human brown adipose tissue (BAT), mostly located in the cervical/supraclavicular region, is a promising target in obesity treatment. Magnetic resonance imaging (MRI) allows for mapping the fat content quantitatively. However, due to the complex heterogeneous distribution of BAT, it has been difficult to establish a standardized segmentation routine based on magnetic resonance (MR) images. Here, we suggest using a multi-modal deep neural network to detect the supraclavicular fat pocket. Methods: A total of 50 healthy subjects [median age/body mass index (BMI) =36 years/24.3 kg/m2] underwent MRI scans of the neck region on a 3 T Ingenia scanner (Philips Healthcare, Best, Netherlands). Manual segmentations following fixed rules for anatomical borders were used as ground truth labels. A deep learning-based method (termed as BAT-Net) was proposed for the segmentation of BAT on MRI scans. It jointly leveraged two-dimensional (2D) and three-dimensional (3D) convolutional neural network (CNN) architectures to efficiently encode the multi-modal and 3D context information from multi-modal MRI scans of the supraclavicular region. We compared the performance of BAT-Net to that of 2D U-Net and 3D U-Net. For 2D U-Net, we analyzed the performance difference of implementing 2D U-Net in three different planes, denoted as 2D U-Net (axial), 2D U-Net (coronal), and 2D U-Net (sagittal). Results: The proposed model achieved an average dice similarity coefficient (DSC) of 0.878 with a standard deviation of 0.020. The volume segmented by the network was smaller compared to the ground truth labels by 9.20 mL on average with a mean absolute increase in proton density fat fraction (PDFF) inside the segmented regions of 1.19 percentage points. The BAT-Net outperformed all implemented 2D U-Nets and the 3D U-Nets with average DSC enhancement ranging from 0.016 to 0.023. Conclusions: The current work integrates a deep neural network-based segmentation into the automated segmentation of supraclavicular fat depot for quantitative evaluation of BAT. Experiments show that the presented multi-modal method benefits from leveraging both 2D and 3D CNN architecture and outperforms the independent use of 2D or 3D networks. Deep learning-based segmentation methods show potential towards a fully automated segmentation of the supraclavicular fat depot.

Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.

A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions. We use LipocyteProfiler to identify known and novel cellular mechanisms altered by polygenic risk of metabolic disease, including insulin resistance, fat distribution, and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse deep phenotypic profiling in lipocytes and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.

Diabetes incidence before and after COVID-19 vaccination - Results from the German Disease Analyzer database.

Objective: We investigated whether COVID-19 vaccination had an impact on diabetes risk. Methods: We used data of 6,198 patients (mean age 64.3 years) from the nationwide Disease Analyzer database, a representative panel of physicians' practices in Germany. Patients received their first COVID-19 vaccination between 1 April 2021 and 31 March 2022, and all were newly diagnosed with diabetes within 183 days before or after this vaccination. Incident rates of diabetes after vaccination were compared to incident rates before vaccination. Results: The incidence rate of diabetes was lower after vaccination than before vaccination (incidence rate ratio = 0.79, 95% confidence interval: 0.75-0.83). The number of incident cases of diabetes was not greater in 2021 than in 2019. Conclusion: Our study did not confirm an increased risk of diabetes after COVID-19 vaccination. Further studies are needed to show whether the vaccination may be associated with a reduced diabetes risk.

The multi-faceted food odorant 4-methylphenol selectively activates evolutionary conserved receptor OR9Q2.

4-Methylphenol is a food-related odor-active volatile with a high recognition factor, due to its horse stable-like, fecal odor quality. Its ambivalent hedonic impact as key aroma compound, malodor, and semiochemical has spurred the search for its cognate, chemosensory odorant receptors across species. A human odorant receptor for the highly characteristic 4-methylphenol has been elusive. Here, we identified and characterized human receptor OR9Q2 to be tuned to purified 4-methylphenol, but not to its contaminant isomer 3-methylphenol. This highly selective function of OR9Q2 complements an exclusive phenol detection gap in the ancient, most broadly tuned human odorant receptor OR2W1. Moreover, a 4-methylphenol function is evolutionary conserved in phylogenetically related OR9Q2 orthologs from chimpanzee, mouse, and cow. Notably, the cow receptor outperformed human OR9Q2 10-fold in signal strength, consonant with previous reports of 4-methylphenol as a bovine pheromone. Our results suggest OR9Q2 as best sensor for the key food odorant, malodor, and semiochemical 4-methylphenol.

Routine care for people with newly diagnosed type 2 diabetes before and during the SARS-CoV-2 pandemic - results from the German Disease Analyzer database.

AIM: To investigate whether the SARS-CoV-2 pandemic affected care for people with newly diagnosed type 2 diabetes in Germany. METHODS: The Disease Analyzer database (IQVIA, Germany) contains routine data on diagnoses and treatments (ICD-10 and ATC codes) from patients followed in selected physician practices across Germany. We compared 21,747 individuals with a first diagnosis of type 2 diabetes between January 2018 and September 2019 with 20,513 individuals with a first diabetes diagnosis between March 2020 and November 2021. RESULTS: In March and April 2020, the number of new diagnoses of diabetes decreased by 18.3% and 35.7%, respectively, compared to March and April of the previous two years. The previous diabetes incidence level was reached again in June 2020. Mean pre-treatment glucose levels were higher during the pandemic than before (fasting plasma glucose: +6.3 mg/dl (95% confidence interval: 4.6-8.0)). In the first six months after diabetes diagnosis, the mean number of GP visits, specialist referrals and HbA1c measurements decreased. CONCLUSION: We observed a decrease in diabetes incidence in the early phase of the pandemic and slightly higher pretreatment blood glucose levels during the pandemic than before. Care for newly diagnosed diabetes was slightly worse during the pandemic than before.

A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes.

Recent large-scale genomic association studies found evidence for a genetic link between increased risk of type 2 diabetes and decreased risk for adiposity-related traits, reminiscent of metabolically obese normal weight (MONW) association signatures. However, the target genes and cellular mechanisms driving such MONW associations remain to be identified. Here, we systematically identify the cellular programmes of one of the top-scoring MONW risk loci, the 2q24.3 risk locus, in subcutaneous adipocytes. We identify a causal genetic variant, rs6712203, an intronic single-nucleotide polymorphism in the COBLL1 gene, which changes the conserved transcription factor motif of POU domain, class 2, transcription factor 2, and leads to differential COBLL1 gene expression by altering the enhancer activity at the locus in subcutaneous adipocytes. We then establish the cellular programme under the genetic control of the 2q24.3 MONW risk locus and the effector gene COBLL1, which is characterized by impaired actin cytoskeleton remodelling in differentiating subcutaneous adipocytes and subsequent failure of these cells to accumulate lipids and develop into metabolically active and insulin-sensitive adipocytes. Finally, we show that perturbations of the effector gene Cobll1 in a mouse model result in organismal phenotypes matching the MONW association signature, including decreased subcutaneous body fat mass and body weight along with impaired glucose tolerance. Taken together, our results provide a mechanistic link between the genetic risk for insulin resistance and low adiposity, providing a potential therapeutic hypothesis and a framework for future identification of causal relationships between genome associations and cellular programmes in other disorders.