Dietary inflammatory potential and arterial stiffness in a French cohort: Insights from the STANISLAS study.

BACKGROUND AND AIMS: Chronic inflammation plays a key role in arterial stiffness pathogenesis. Dietary components can display anti- or pro-inflammatory properties. Nonetheless, the association between the diet's overall inflammatory potential and arterial stiffness is unclear. This study aimed to assess the association between the diet's overall inflammatory potential and arterial stiffness assessed by carotid-femoral pulse wave velocity (cfPWV). METHODS AND RESULTS: This cross-sectional study included 1307 participants from the STANISLAS family cohort study. Dietary data were collected using a validated food frequency questionnaire. The adapted dietary inflammatory index (ADII) score was calculated to assess the inflammatory potential of the participants' diet. The association of ADII score quartile with cfPWV was assessed using IPW-weighted linear mixed models with random family effect. The median (Q1-Q3) ADII score was 0.45 (-1.57, 2.04). Participants exhibiting higher ADII scores demonstrated elevated energy intake, dietary saturated fat, and ultra-processed foods. Conversely, individuals with lower ADII scores exhibited higher vitamins and omega intakes, and a higher diet quality, as assessed by the DASH score. Despite these observations from the descriptive analyses, ADII score quartiles were not significantly associated with cfPWV (ß(95% CI) were 0.01 (-0.02,0.04) for Q2, 0.02 (-0.01,0.05) for Q3, and 0.02 (-0.01,0.05) for Q4 compared to Q1). CONCLUSION: In this cross-sectional study, participants had a relatively modest consumption of pro-inflammatory foods, no substantial associations were observed between the diet inflammatory potential and arterial stiffness. Further longitudinal studies in larger cohorts are needed to better understand the link between inflammatory diet and arterial stiffness.

Barriers to metabolic surgery and how to address them.

After bariatric surgery, patients with obesity achieve sustainable weight loss, gain in mobility, quality of life and life expectancy. Bariatric surgery can lead to remission of type 2 diabetes or to long term glycaemic control for patients with type 2 diabetes, while medical treatment has a preventive efficacy on micro and macrovascular complications. This has led to the concept of metabolic surgery to treat type 2 diabetes. Despite the benefits, only a small proportion of eligible patients undergo bariatric/metabolic surgery. Powerful antidiabetic medications, self-estimated lack of knowledge by medical professionals and fear of surgical complications are some of the arguments to prefer medical treatment of type 2 diabetes obesity versus metabolic surgery. We have reviewed in this paper the barriers which explain the low referral rate to metabolic surgery. With the point of view of the diabetologist, the general practitioner and the patient, we have addressed them to help clinicians and patients model an evidenced-based patient-oriented medical plan.

Out-of-Pocket Expenses in Households of People Living with Obesity in France.

BACKGROUND/OBJECTIVES: Overweight and obesity result in a substantial economic burden in both low- and high-income countries. Moreover, this burden is often underestimated because it only partially accounts for unreimbursed out-of-pocket expenses (OOPE) related to obesity. The objective of our study was not only to evaluate OOPE incurred by people with obesity in relation to their disease with respect to direct medical expenditures and direct non-medical expenditures but also the proportion of people living with obesity who have forgone obesity-related healthcare due to the costs of such care. METHODS: An observational descriptive survey was conducted among people with class II/III obesity attending six obesity treatment centers in France. Volunteer adult participants completed a written/phone questionnaire on their related expenditures over the last 6 months for current expenditures and over the last 5 years for occasional ones. The costs were expressed in 2022 EUR. RESULTS: 299 people participated (age: 46 years [SD: 13.9], women: 72%, BMI ≥40 kg/m2: 62% and 48% with comorbidities). 65% had a professional activity. 83% declared that they had OOPE related to obesity representing annually EUR 2027/individual on average (5% of the household revenue), including weight loss and nutritional products, vitamins, meal programs, gym memberships, psychologists, but mainly adapted clothing, additional travel costs, and others. 15% of the respondents had to modify their professional activity due to obesity and 15% forwent some medical care in the last 12 months. CONCLUSIONS: OOPE is a significant part of the economic burden of obesity. Despite some limitations due to the specificities of the participants and because some costs may be more related to social activities affected by obesity than to healthcare, it seems important to consider these expenditures in cost estimates for obesity.

Metabolic signature of 13C-labeled wheat bran consumption related to gut fermentation in humans: a pilot study.

PURPOSE: The aim of this pilot study was to analyze concomitantly the kinetics of production of 13C-labeled gut-derived metabolites from 13C-labeled wheat bran in three biological matrices (breath, plasma, stools), in order to assess differential fermentation profiles among subjects. METHODS: Six healthy women consumed a controlled breakfast containing 13C-labeled wheat bran biscuits. H2, CH4 and 13CO2, 13CH4 24 h-concentrations in breath were measured, respectively, by gas chromatography (GC) and GC-isotope ratio mass spectrometry (GC-IRMS). Plasma and fecal concentrations of 13C-short-chain fatty acids (linear SCFAs: acetate, propionate, butyrate, valerate; branched SCFAs: isobutyrate, isovalerate) were quantified using GC-combustion-IRMS. Gut microbiota composition was assessed by16S rRNA gene sequencing analysis. RESULTS: H2 and CH4 24 h-kinetics distinguished two groups in terms of fermentation-related gas excretion: high-CH4 producers vs low-CH4 producers (fasting concentrations: 45.3 ± 13.6 ppm vs 6.5 ± 3.6 ppm). Expired 13CH4 was enhanced and prolonged in high-CH4 producers compared to low-CH4 producers. The proportion of plasma and stool 13C-butyrate tended to be higher in low-CH4 producers, and inversely for 13C-acetate. Plasma branched SCFAs revealed different kinetics of apparition compared to linear SCFAs. CONCLUSION: This pilot study allowed to consider novel procedures for the development of biomarkers revealing dietary fiber-gut microbiota interactions. The non-invasive assessment of exhaled gas following 13C-labeled fibers ingestion enabled to decipher distinct fermentation profiles: high-CH4 producers vs low-CH4 producers. The isotope labeling permits a specific in vivo characterisation of the dietary fiber impact consumption on microbiota metabolite production. CLINICAL TRIAL REGISTRATION: The study has been registered under the number NCT03717311 at ClinicalTrials.gov on October 24, 2018.

Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial.

The adaptive response to overfeeding is associated with profound modifications of gene expression in adipose tissue to support lipid storage and weight gain. The objective of this study was to assess in healthy lean men whether a supplementation with polyphenols could interact with these molecular adaptations. Abdominal subcutaneous adipose tissue biopsies were sampled from 42 subjects participating to an overfeeding protocol providing an excess of 50% of their total energy expenditure for 31 days, and who were supplemented with 2 g/day of grape polyphenols or a placebo. Gene expression profiling was performed by RNA sequencing. Overfeeding led to a modification of the expression of 163 and 352 genes in the placebo and polyphenol groups, respectively. The GO functions of these genes were mostly involved in lipid metabolism, followed by genes involved in adipose tissue remodeling and expansion. In response to overfeeding, 812 genes were differentially regulated between groups. Among them, a set of 41 genes were related to angiogenesis and were down-regulated in the polyphenol group. Immunohistochemistry targeting PECAM1, as endothelial cell marker, confirmed reduced angiogenesis in this group. Finally, quercetin and isorhamnetin, two polyphenol species enriched in the plasma of the volunteers submitted to the polyphenols, were found to inhibit human umbilical vein endothelial cells migration in vitro. Polyphenol supplementation do not prevent the regulation of genes related to lipid metabolism in human adipose tissue during overfeeding, but impact the angiogenesis pathways. This may potentially contribute to a protection against adipose tissue expansion during dynamic phase of weight gain.

Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort.

BACKGROUND: Patients with diabetes and obesity are populations at high-risk for severe COVID-19 outcomes and have shown blunted immune responses when administered different vaccines. Here we used the 'ANRS0001S COV-POPART' French nationwide multicenter prospective cohort to investigate early humoral response to COVID-19 vaccination in the sub-cohort ('COVPOP OBEDIAB') of patients with obesity and diabetes. METHODS: Patients with diabetes (n = 390, type 1 or 2) or obesity (n = 357) who had received two vaccine doses and had no history of previous COVID-19 infection and negative anti-nucleocapsid (NCP) antibodies were included and compared against healthy subjects (n = 573). Humoral response was assessed at baseline, at one month post-first dose (M0) and one-month post-second dose (M1), through percentage of responders (positive anti-spike SARS-CoV-2 IgG antibodies (Sabs), geometric means of Sabs; BAU/mL), proportion of individuals with anti-RBD antibodies, and proportion of individuals with anti-SARS-CoV-2-specific neutralizing antibodies (Nabs). Potential clinical and biological factors associated with weak response (defined as Sabs < 264 BAU/mL) and presence of non-reactive anti-RBD antibodies at M1 were evaluated. Univariate and multivariate regressions were performed to estimate crude and adjusted coefficients with 95 % confidence intervals. Poor glycemic control was defined as HbA1c ≥ 7.5 % at inclusion. RESULTS: Patients with diabetes, particularly type 2 diabetes, and patients with obesity were less likely to have positive Sabs and anti-RBD antibodies after the first and second dose compared to controls (p < 0.001). At M1, we found Sabs seroconversion in 94.1 % of patients with diabetes versus 99.7 % in controls, anti-RBD seroconversion in 93.8 % of patients with diabetes versus 99.1 % in controls, and Nabs seroconversion in 95.7 % of patients with diabetes versus 99.6 % in controls (all p < 0.0001). Sabs and anti-RBD seroconversion at M0 and M1 were also significantly lower in obese patients than controls, at respectively 82.1 % versus 89.9 % (p = 0.001; M0 Sabs), 94.4 % versus 99.7 % (p 0.001; M1 Sabs), 79.0 % vs 86.2 % (p = 0.004 M0 anti-RBD), and 96.99 % vs 99.1 % (p = 0.012 M1 anti-RBD). The factors associated with low vaccine response (BAU < 264/mL) in patients with diabetes were chronic kidney disease (adjusted OR = 6.88 [1.77;26.77], p = 0.005) and poor glycemic control (adjusted OR = 3.92 [1.26;12.14], p = 0.018). In addition, BMI ≥ 40 kg/m2 was found to be associated with a higher vaccine response (adjusted OR = 0.10 [0.01;0.91], p = 0.040) than patients with BMI < 40 kg/m2. CONCLUSION: COVID-19 vaccine humoral response was lower in patients with obesity and diabetes one month after second dose compared to controls, especially in diabetic patients with CKD or inadequate glycemic control. These findings point to the need for post-vaccination serological checks in these high-risk populations.

Association between eating behaviour and 13-year cardiovascular damages in the initially healthy STANISLAS cohort.

AIMS: Several dimensions of eating behaviour (EB), such as restrained eating (RE), appear to be cross-sectionally associated with certain cardiovascular (CV) diseases and metabolic risk factors although little is known regarding longitudinal associations. This study aimed to assess the associations between EB and CV damage or metabolic syndrome after 13 years, in initially healthy individuals. METHODS AND RESULTS: This study included 1109 participants from the familial STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort study. Emotional eating (EmE), RE, and external eating were assessed using the Dutch Eating Behaviour Questionnaire. Metabolic syndrome and CV damages such as carotid-femoral pulse-wave velocity (cfPWV), left ventricular mass, carotid intima-media thickness, and diastolic dysfunction (DD) were measured after a period of 13 years. Mixed model analysis with a family random effect and adjustment for age, sex, education, temporal gap, physical activity, metabolic factors at baseline, and the onset of CV disease during follow-up, and mediation analysis were performed in adults and adolescents separately. Among adults, EmE was associated with a 38% increased risk of DD 13 years later [odds ratio = 1.38 (1.05; 1.83)]. Stress level mediated 31.9% of this association (P = 0.01). Emotional eating was positively associated with cfPWV (ß=0.02 [0.01; 0.04]). External eating was slightly associated with lower cfPWV (ß=-0.03 [-0.05; -0.01]). No associations were observed between EB dimensions and metabolic syndrome. Energy intake was not found to be a mediator of any associations. CONCLUSION: Our results suggest that CV prevention should also take into account EB and include emotion regulation skills teaching.

The association of three dimensions of eating behaviour [emotional eating, restrained eating, and external eating] with 13 years later cardiovascular damages have been investigated in the initially healthy STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort. Emotional eating was associated with higher pulse-wave velocity and an increased risk of diastolic dysfunction. External eating was associated with lower pulse-wave velocity. Stress level was found to be a mediator of the association found between emotional eating and diastolic dysfunction.

One-month humoral response following two or three doses of messenger RNA coronavirus disease 2019 vaccines as primary vaccination in specific populations in France: first results from the Agence Nationale Recherche contre le Sida (ANRS)0001S COV-POPART cohort.

OBJECTIVES: We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults. METHODS: Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized. RESULTS: We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies. CONCLUSIONS: A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies.

Grape polyphenols decrease circulating branched chain amino acids in overfed adults.

Introduction and aims: Dietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials. Methods: Blood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov. Results: Changes in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study. Conclusion: Administration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.

Fatty acid desaturase genetic variations and dietary omega-3 fatty acid intake associate with arterial stiffness.

Aims: Long-chain polyunsaturated fatty acids (PUFAs) generate diverse bioactive lipid mediators, which tightly regulate vascular inflammation. The effects of omega-3 PUFA supplementation in cardiovascular prevention however remain controversial. In addition to direct dietary intake, fatty acid desaturases (FADS) determine PUFA levels. Increased arterial stiffness represents an independent predictor of mortality and cardiovascular events. The aim of the present study was to determine the association of PUFA intake, FADS1 genotype, and FADS expression with arterial stiffness. Methods and results: A cross-sectional population-based cohort study of 1464 participants without overt cardiovascular disease was conducted. Dietary intake was assessed using a food frequency questionnaire. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), and the FADS1 locus variant was determined. Blood cell transcriptomics was performed in a subset of 410 individuals. Pulse wave velocity was significantly associated with the FADS1 locus variant. Differential associations between PWV and omega-3 PUFA intake were observed depending on the FADS1 genotype. High omega-3 PUFA intake attenuated the FADS1 genotype-dependent associations. Carriers of the minor FADS1 locus variant exhibited increased expression of FADS2, which is associated with PWV. Conclusion: Taken together, these findings point to FADS1 genotype-dependent associations of omega-3 PUFA intake on subclinical cardiovascular disease. These findings may have implications for identifying responders and non-responders to omega-3 PUFA supplementation and open up for personalized dietary counselling in cardiovascular prevention.

Breath volatile metabolome reveals the impact of dietary fibres on the gut microbiota: Proof of concept in healthy volunteers.

BACKGROUND: Current data suggest that dietary fibre (DF) interaction with the gut microbiota largely contributes to their physiological effects. The bacterial fermentation of DF leads to the production of metabolites, most of them are volatile. This study analyzed the breath volatile metabolites (BVM) profile in healthy individuals (n=15) prior and after a 3-week intervention with chitin-glucan (CG, 4.5 g/day), an insoluble fermentable DF. METHODS: The present exploratory study presents the original data related to the secondary outcomes, notably the analysis of BVM. BVM were analyzed throughout the test days -in fasting state and after standardized meals - using selected ion flow tube mass spectrometry (SIFT-MS). BVM production was correlated to the gut microbiota composition (Illumina sequencing, primary outcome), analyzed before and after the intervention. FINDINGS: The data reveal that the post-prandial state versus fasting state is a key determinant of BVM fingerprint. Correlation analyses with fecal microbiota spotlighted butyrate-producing bacteria, notably Faecalibacterium, as dominant bacteria involved in butyrate and other BVM expiration. CG intervention promotes interindividual variations of fasting BVM, and decreases or delays the expiration of most exhaled BVM in favor of H2 expiration, without any consequence on gastrointestinal tolerance. INTERPRETATION: Assessing BVM is a non-invasive methodology allowing to analyze the influence of DF intervention on the gut microbiota. FUNDING: FiberTAG project was initiated from a European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL) and was supported by the Service Public de Wallonie (SPW-EER, convention 1610365, Belgium).

Polyphenol Supplementation Did Not Affect Insulin Sensitivity and Fat Deposition During One-Month Overfeeding in Randomized Placebo-Controlled Trials in Men and in Women.

Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with [1,1,1-13C3]-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://clinicaltrials.gov/ct2/show/NCT02145780 and https://clinicaltrials.gov/ct2/show/NCT02225457.

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial.

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk.

Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q < 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (-0.42 mM; q < 0.01), LDL cholesterol (-0.36 mM; q < 0.01), insulin (-2.77 mIU/l; q < 0.05), and HOMA (-0.78; q < 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.

[Psychiatric disorders and bariatric surgery]. / Troubles psychiatriques et chirurgie bariatrique.

PSYCHIATRIC DISORDERS AND BARIATRIC SURGERY Psychiatric disorders are common in people with obesity and their lifetime prevalence is estimated to range from 30 % to 70 %. The most frequently reported disorders are mood and anxiety disorders, attention deficit disorder, and binge eating disorder. These disorders will usually improve after bariatric surgery and do not appear to have a significant negative impact on weight loss. However, increased attention is needed regarding some aspects of these disorders (e. G., emotional dysregulation, impulsivity) as well as regarding the increased risk of developing a substance abuse disorder or increased suicide risk after bariatric surgery. As well as a high quality pre-operative psychiatric assessment is required, post-operative psychiatric follow-up is required.

TROUBLES PSYCHIATRIQUES ET CHIRURGIE BARIATRIQUE Les troubles psychiatriques sont fréquents en cas d'obésité, et leur prévalence est estimée entre 30 et 70 %. Les plus fréquents sont les troubles de l'humeur, les troubles anxieux, le trouble du déficit de l'attention, et l'hyperphagie boulimique. La plupart d'entre eux s'améliorent après une chirurgie bariatrique et ne semblent pas affecter de façon importante le pronostic pondéral. Cependant, un regain de vigilance s'impose quant à certaines composantes de ces troubles (par exemple la dysrégulation émotionnelle, l'impulsivité) et devant une augmentation des risques de développer une addiction et de suicide après une chirurgie bariatrique. Au-delà de la nécessité d'une évaluation psychiatrique préopératoire de qualité, un suivi psychiatrique postopératoire apparaît de plus en plus nécessaire, ne serait-ce que pour identifier les risques émergents.

CGMS and Glycemic Variability, Relevance in Clinical Research to Evaluate Interventions in T2D, a Literature Review.

Glycemic variability (GV) appears today as an integral component of glucose homeostasis for the management of type 2 diabetes (T2D). This review aims at investigating the use and relevance of GV parameters in interventional and observational studies for glucose control management in T2D. It will first focus on the relationships between GV parameters measured by continuous glucose monitoring system (CGMS) and glycemic control and T2D-associated complications markers. The second part will be dedicated to the analysis of GV parameters from CGMS as outcomes in interventional studies (pharmacological, nutritional, physical activity) aimed at improving glycemic control in patients with T2D. From 243 articles first identified, 63 articles were included (27 for the first part and 38 for the second part). For both analyses, the majority of the identified studies were pharmacological. Lifestyle studies (including nutritional and physical activity-based studies, N-AP) were poorly represented. Concerning the relationships of GV parameters with those for glycemic control and T2D related-complications, the standard deviation (SD), the coefficient of variation (CV), the mean blood glucose (MBG), and the mean amplitude of the glycemic excursions (MAGEs) were the most studied, showing strong relationships, in particular with HbA1c. Regarding the use and relevance of GV as an outcome in interventional studies, in pharmacological ones, SD, MAGE, MBG, and time in range (TIR) were the GV parameters used as main criteria in most studies, showing significant improvement after intervention, in parallel or not with glycemic control parameters' (HbA1c, FBG, and PPBG) improvement. In N-AP studies, the same results were observed for SD, MAGE, and TIR. Despite the small number of N-AP studies addressing both GV and glycemic control parameters compared to pharmacological ones, N-AP studies have shown promising results on GV parameters and would require more in-depth work. Evaluating CGMS-GV parameters as outcomes in interventional studies may provide a more integrative dimension of glucose control than the standard postprandial follow-up. GV appears to be a key component of T2D dysglycemia, and some parameters such as MAGE, SD, or TIR could be used routinely in addition to classical markers of glycemic control such as HbA1c, fasting, or postprandial glycemia.

Long-term outcomes of bariatric surgery in patients with bi-allelic mutations in the POMC, LEPR, and MC4R genes.

BACKGROUND: Gene mutations in the leptin-melanocortin signaling cascade lead to hyperphagia and severe early onset obesity. In most cases, multimodal conservative treatment (increased physical activity, reduced caloric intake) is not successful to stabilize body weight and control hyperphagia. OBJECTIVES: To examine bariatric surgery as a therapeutic option for patients with genetic obesity. SETTING: Three major academic, specialized medical centers. METHODS: In 3 clinical centers, we retrospectively analyzed the outcomes of bariatric surgery performed in 8 patients with monogenic forms of obesity with bi-allelic variants in the genes LEPR (n = 5), POMC (n = 2), and MC4R (n = 1). RESULTS: In this group of patients with monogenic obesity, initial bariatric surgery was performed at a median age of 19 years (interquartile range [IQR], 16-23.8 yr). All patients initially experienced weight loss after each bariatric surgery, which was followed by substantial weight regain. In total, bariatric surgery led to a median maximum reduction of body weight of -21.5 kg (IQR, -36.3 to -2.9 kg), median percent excess weight loss (%EWL) of -47.5 %EWL (IQR, -57.6 to -28.9 %EWL). This body weight reduction was followed by median weight regain of 24.1 kg (IQR: 10.0 to 42.0 kg), leading to a final weight change of -24.2 % EWL (IQR: -37.6 to -5.4 %EWL) after a maximum duration of 19 years post surgery. In one patient, bariatric surgery was accompanied by significant complications, including vitamin deficiencies and hernia development. CONCLUSION: The indication for bariatric surgery in patients with monogenic obesity based on bi-allelic gene mutations and its benefit/risk balance has to be evaluated very cautiously by specialized centers. Furthermore, to avoid an unsuccessful operation, preoperative genetic testing of patients with a history of early onset obesity might be essential, even more since novel pharmacological treatment options are expected.

Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women.

BACKGROUNDHigh circulating levels of ceramides (Cer) and sphingomyelins (SM) are associated with cardiometabolic diseases. The consumption of whole fat dairy products, naturally containing such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown.METHODSIn a 4-week randomized controlled trial, 58 postmenopausal women daily consumed milk PL-enriched cream cheese (0, 3, or 5 g of milk PL). Postprandial metabolic explorations were performed before and after supplementation. Analyses included SM and Cer species in serum, chylomicrons, and feces. The ileal contents of 4 ileostomy patients were also explored after acute milk PL intake.RESULTSMilk PL decreased serum atherogenic C24:1 Cer, C16:1 SM, and C18:1 SM species (Pgroup < 0.05). Changes in serum C16+18 SM species were positively correlated with the reduction of cholesterol (r = 0.706), LDL-C (r = 0.666), and ApoB (r = 0.705) (P < 0.001). Milk PL decreased chylomicron content in total SM and C24:1 Cer (Pgroup < 0.001), parallel to a marked increase in total Cer in feces (Pgroup < 0.001). Milk PL modulated some specific SM and Cer species in both ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSIONMilk PL supplementation decreased atherogenic SM and Cer species associated with the improvement of cardiovascular risk markers. Our findings bring insights on sphingolipid metabolism in the gut, especially Cer, as signaling molecules potentially participating in the beneficial effects of milk PL.TRIAL REGISTRATIONClinicalTrials.gov, NCT02099032, NCT02146339.FUNDINGANR-11-ALID-007-01; PHRCI-2014: VALOBAB, no. 14-007; CNIEL; GLN 2018-11-07; HCL (sponsor).

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial.

PURPOSE: Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients. METHODS: Microbiota (16S rRNA sequencing), long- and short-chain fatty acids (LCFA, SCFA), bile acids, zonulin, and calprotectin were analyzed in fecal samples obtained from obese patients included in a randomized, placebo-controlled trial. Participants received either 16 g/d native inulin (prebiotic n = 12) versus maltodextrin (placebo n = 12), coupled to dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction. RESULTS: Both placebo and prebiotic interventions lowered energy and protein intake. A substantial increase in Bifidobacterium was detected after ITF treatment (q = 0.049) supporting our recent data obtained in a larger cohort. Interestingly, fecal calprotectin, a marker of gut inflammation, was reduced upon ITF treatment. Both prebiotic and placebo interventions increased the ratio of tauro-conjugated/free bile acids in feces. Prebiotic treatment did not significantly modify fecal SCFA content but it increased fecal rumenic acid, a conjugated linoleic acid (cis-9, trans-11 CLA) with immunomodulatory properties, that correlated notably to the expansion of Bifidobacterium (p = 0.031; r = 0.052). CONCLUSIONS: Our study demonstrates that ITF-prebiotic intake during 3 months decreases a fecal marker of intestinal inflammation in obese patients. Our data point to a potential contribution of microbial lipid-derived metabolites in gastro-intestinal dysfunction related to obesity. CLINICALTRIALS. GOV IDENTIFIER: NCT03852069 (February 22, 2019 retrospectively, registered).