Impact of metformin and Dysosmobacter welbionis on diet-induced obesity and diabetes: from clinical observation to preclinical intervention.

AIMS/HYPOTHESIS: We aimed to investigate the association between the abundance of Dysosmobacter welbionis, a commensal gut bacterium, and metabolic health in human participants with obesity and diabetes, and the influence of metformin treatment and prebiotic intervention. METHODS: Metabolic variables were assessed and faecal samples were collected from 106 participants in a randomised controlled intervention with a prebiotic stratified by metformin treatment (Food4Gut trial). The abundance of D. welbionis was measured by quantitative PCR and correlated with metabolic markers. The in vitro effect of metformin on D. welbionis growth was evaluated and an in vivo study was performed in mice to investigate the effects of metformin and D. welbionis J115T supplementation, either alone or in combination, on metabolic variables. RESULTS: D. welbionis abundance was unaffected by prebiotic treatment but was significantly higher in metformin-treated participants. Responders to prebiotic treatment had higher baseline D. welbionis levels than non-responders. D. welbionis was negatively correlated with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and fasting blood glucose levels in humans with obesity and type 2 diabetes. In vitro, metformin had no direct effect on D. welbionis growth. In mice, D. welbionis J115T treatment reduced body weight gain and liver weight, and improved glucose tolerance to a better level than metformin, but did not have synergistic effects with metformin. CONCLUSIONS/INTERPRETATION: D. welbionis abundance is influenced by metformin treatment and associated with prebiotic response, liver health and glucose metabolism in humans with obesity and diabetes. This study suggests that D. welbionis may play a role in metabolic health and warrants further investigation. CLINICAL TRIAL: NCT03852069.

[Prevention of type 2 diabetes and its complications]. / Prévention du diabète de type 2 et de ses complications.

Type 2 diabetes (T2D) represents a major medical and public health problem. The ability to prevent or delay T2D by modifying some of its risk factors has been hypothesized for several decades. Indeed, the slow and gradual deterioration of glycaemia prior to the diabetes diagnosis constitutes a period during which interventions could be effective in preventing T2D. Lifestyle modifications demonstrated that modest weight loss (at least 7% of initial weight) and moderate to intense physical activity of at least 150 minutes per week, markedly and significantly delayed the onset of T2D in subjects at high risk of developing the disease. Pharmacological interventions indicated that metformin should be considered, particularly in young patients (< 60 years) with a body mass index ≥ 35 kg/m², and in women with a history of gestational diabetes. Bariatric surgery, which allows significant weight loss in subjects with severe or morbid obesity, has also demonstrated important preventive effectiveness and metabolic surgery in now considered in at-risk patients with less severe obesity. In conclusion, in overweight or obese adults at high risk of developing T2D, treatment aimed at losing weight (including bariatric surgery) and increasing physical activity should be implemented, and a pharmacotherapy might be considered case by case.

Le diabète de type 2 (DT2) constitue un problème majeur, tant au niveau médical individuel qu'en termes de santé publique. La capacité de prévenir ou retarder le DT2 en modifiant certains facteurs de risque est une hypothèse envisagée depuis plusieurs décennies. En effet, la lente et graduelle détérioration de la glycémie avant le diagnostic de diabète constitue une période au cours de laquelle des interventions pourraient se révéler efficaces. Les modifications de comportement concernant le mode de vie ont démontré qu'une perte de poids modeste (au moins 7 % du poids initial) et une activité physique modérée à intense d'au moins 150 minutes par semaine retardaient, de manière importante et significative, l'apparition du DT2 chez des sujets à haut risque de développer la maladie. Au niveau médicamenteux, la metformine s'est également révélée efficace, en particulier chez les patients jeunes (< 60 ans) avec un indice de masse corporelle ≥ 35 kg/m², et chez les femmes avec des antécédents de diabète gestationnel. La chirurgie bariatrique, qui permet d'obtenir une perte de poids importante chez les sujets avec obésité sévère ou morbide, a également démontré une grande efficacité pour prévenir la survenue d'un DT2. Une chirurgie métabolique est même maintenant envisagée chez des sujets à risque avec une obésité moins sévère. En conclusion, chez les adultes en surpoids ou obèses à haut risque de développer un DT2, une prise en charge visant à perdre du poids (y compris via la chirurgie bariatrique) et augmenter l'activité physique devrait être mise en place, couplée le cas échéant à une approche pharmacologique.

[Patient with type 2 diabetes and coronary heart disease developing heart failure]. / Vignette thérapeutique de l'étudiant. Patient avec un diabète de type 2, une coronaropathie et une insuffisance cardiaque.

Patients with type 2 diabetes (T2D) are frequently exposed to comorbidities, mainly cardiovascular complications. Thus, a polypharmacy is often mandatory, targeting not only T2D but also comorbidities such as coronary artery disease and heart failure. Interestingly, some drugs improve glucose control, cardiovascular prognosis and heart failure outcome. This versatility may cause trouble regarding prescriptions by practitioners, especially because of the restricted conditions for the reimbursement in Belgium. This clinical vignette aims at discussing the path of pharmacotherapy for a patient with T2D who suffers from a myocardial infarction and subsequently develops a heart failure. It will mainly focus on the place of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporters 2 (gliflozins) as well as the potential of their combination in this context, considering the current restrictions for the reimbursement.

Le patient avec un diabète de type 2 (DT2) est souvent exposé à diverses comorbidités, notamment cardiovasculaires. Dès lors, une polymédication est souvent nécessaire, ciblant le DT2 lui-même, mais aussi les comorbidités comme une coronaropathie et une insuffisance cardiaque. De façon intéressante, certaines médications améliorent à la fois le contrôle glycémique, le pronostic cardiovasculaire et le devenir de l'insuffisance cardiaque. Cette polyvalence peut jeter le trouble en ce qui concerne les prescriptions chez les praticiens, notamment en lien avec les conditions restrictives de remboursement en Belgique. Cette vignette clinique a pour but d'illustrer le cheminement de la pharmacothérapie d'un patient avec un DT2 qui présente un infarctus du myocarde puis, secondairement, une insuffisance cardiaque. Elle ciblera surtout la place des agonistes des récepteurs du glucagon-like peptide-1 et des inhibiteurs des cotransporteurs sodium-glucose de type 2 (gliflozines), et expliquera l'intérêt de leur combinaison dans ce contexte en tenant compte des conditions actuelles de remboursement.

[Don't neglect metabolic syndrome]. / Vignette diagnostique de l'étudiant. Ne pas négliger le syndrome métabolique.

The concept of «metabolic syndrome¼ was brought to the forefront in the early 2000s in international literature, but this interest seems to have faded somewhat in recent years. However, this constellation of cardiovascular risk factors should not be neglected. Taken individually, they hardly seem problematic, but when they are present within the same individual, they significantly increase the risk of cardiovascular morbidity and mortality. This clinical vignette aims to draw attention to the usefulness of the search for metabolic syndrome in clinical practic.

Le concept de «syndrome métabolique¼ a été mis en avant de la scène au début des années 2000 dans la littérature internationale, mais cet intérêt semble s'être quelque peu estompé au cours des dernières années. Il convient cependant de ne pas négliger cette constellation de facteurs de risque cardiovasculaire qui, pris individuellement, ne paraissent guère problématiques, mais qui, lorsqu'ils co-existent chez une même personne, augmentent sensiblement le risque de morbi-mortalité. Cette vignette clinique a pour but d'attirer l'attention sur l'importance de la recherche d'un syndrome métabolique dans la pratique clinique.

What is the nutritional status of patients with prolonged disorders of consciousness? A retrospective cross-sectional study.

BACKGROUND: Nutritional status of patients with disorders of consciousness (DoC) is poorly studied. OBJECTIVES: To evaluate the relationship between nutritional status (body mass index, daily calories intake) and clinical variables (level of consciousness, time since injury, diagnosis, etiology and spastic muscle overactivity; SMO,) in patients with prolonged DoCor emerging. Our main hypotheses are i) patients with lower level of consciousness (UWS) have worse nutritional status compared to patients in minimally conscious state (MCS) and ii) SMO could influence nutritional status. METHODS AND RESULTS: Among the 80 patients included in the study (19 UWS, 47 MCS, 14 emerging MCS; 43 ± 15 yo; 3 ± 4 years post-injury, 35 traumatic etiology, 34 females), 9% were at risk to be undernourished, with no differences between UWS and MCS. Patients without SMO had a higher BMI compared to patients with severe SMO. Compared to the recommended daily calories intake, patients with the highest BMI received less calories and patients with the lowest BMI received more calories. We observed a negative correlation between SMO (in lower limbs) and BMI. CONCLUSION: Our study shows that most patients are well nourished, independently from the level of consciousness. SMO may require additional calories in patients' daily needs; however, longitudinal studies are needed to explore the causal relationship between these variables.

[Reactive hypoglycaemia, a frequently mentioned functional disorder, yet overestimated in clinical practice]. / L'hypoglycémie réactionnelle : un trouble fonctionnel fréquemment évoqué, mais surestimé en pratique clinique.

Malaises are often attributed to hypoglycaemia in nondiabetic people who don't have any other serious medical problem. Reactive hypoglycaemia, the most frequent one, may be considered as a functional disorder. However, its diagnosis is often overused, because not really demonstrated in most instances. The diagnosis of hypoglycaemia should be structured, based upon the Whipple triad. First, the medical interrogatory must search for adrenergic and neuroglucopenic symptoms that suggest hypoglycaemia. Second, if the malaise is due to a hypoglycaemia, it should resume rapidly after the administration of sugar. Third, hypoglycaemia must be confirmed by a measurement of a low glucose level at the time of a malaise. The latter approach is facilitated by the use of home blood monitoring, a strategy that is now preferred to the use of an oral glucose tolerance test, a non-physiological test far from real-life conditions. When the diagnosis is made based upon this triad, the medical interview should precise the severity of the symptoms and focus on the chronology of the malaises, typically 2-3 hours after a sugar-enriched meal in case of a reactive hypoglycaemia. Therapeutic approach of this functional disorder mostly relies on dietary advices.

La survenue de malaises est souvent attribuée à une hypoglycémie chez des personnes non diabétiques et, a priori, sans autre problème de santé. L'hypoglycémie réactionnelle, la plus fréquente, peut être considérée comme un trouble fonctionnel. Son diagnostic est, cependant, souvent galvaudé, car l'hypoglycémie n'est habituellement pas authentifiée. Le diagnostic d'hypoglycémie doit se faire de façon structurée en se basant sur la «triade de Whipple¼. Tout d'abord, l'anamnèse doit rechercher les symptômes évocateurs d'hypoglycémie, adrénergiques et neuroglucopéniques. Ensuite, s'il s'agit bien d'une hypoglycémie, le malaise doit disparaître rapidement après resucrage. Enfin, l'hypoglycémie doit être authentifiée par une mesure d'une valeur basse au moment d'un malaise. Cette confirmation a été facilitée par l'utilisation des lecteurs de glycémie, une stratégie qui est dorénavant préférée à la réalisation d'une hyperglycémie provoquée par voie orale, test non physiologique fort éloigné des conditions de vraie vie. Une fois le diagnostic posé sur cette triade, l'anamnèse doit faire préciser, outre la sévérité des malaises, leur chronologie, typiquement 2-3 heures après un repas riche en glucides dans le cas d'une hypoglycémie réactive. Le traitement de ce trouble fonctionnel repose principalement sur des mesures diététiques.

[Anti-obesity drugs : from previous disappointments to new hopes]. / Médicaments anti-obésité : des déceptions aux espoirs.

Both physicians and patients dream of an efficacious and safe pharmacological approach to treat obesity. Unfortunately, most anti-obesity drugs prescribed since the fifties were associated with an unfavourable risk profile that led to numerous withdrawals. Medications issued from pharmaco-chemistry that mainly target brain amines to reduce appetite have been abandoned because of potential cardiovascular and neuropsychiatric toxicities. More recently, biological medications emerged, especially GLP-1 (Glucagon-Like Peptide-1) receptor agonists, well-known to manage type 2 diabetes and now recommended at higher doses for the treatment of obesity (liraglutide, semaglutide). A dual agonist that targets both GLP-1 and GIP (Glucose-dependent Insulinotropic Polypeptide) receptors (tirzepatide) appears to be even more potent as glucose-lowering agent and is currently tested as an anti-obesity agent. Many other pharmacological approaches are currently investigated but they should not mask the importance of life-style measurements.

Médecins et patients rêvent d'une approche pharmacologique efficace et sûre pour traiter l'obésité. Hélas, la plupart des médicaments anti-obésité testés depuis les années 50 ont été grevés d'un profil de risque défavorable, ce qui a amené de nombreux retraits du marché. Les médicaments issus de la pharmacochimie ciblant principalement les amines cérébrales pour freiner l'appétit ont été abandonnés en raison de leur toxicité potentielle, cardiovasculaire et neuropsychiatrique. Une nouvelle opportunité est offerte avec l'avènement de médicaments biologiques, en particulier des analogues du GLP-1 (Glucagon-Like Peptide-1) bien connus pour traiter le diabète de type 2 et aussi commercialisés à plus fortes doses pour traiter l'obésité (liraglutide, sémaglutide). Un agoniste double ciblant à la fois les récepteurs du GLP-1 et du GIP («Glucose-dependent Insulinotropic Polypeptide¼), le tirzépatide, s'avère encore plus puissant comme médicament antidiabétique et est actuellement testé comme agent anti-obésité. Un grand nombre d'autres approches pharmacologiques sont en cours d'investigation, mais toutes ces initiatives ne doivent pas scotomiser l'importance des mesures hygiéno-diététiques.

[Update of nutritional recommendations in the treatment of type 2 diabetes]. / Actualisation des recommandations nutritionnelles dans le traitement du diabète de type 2.

Dietary management of type 2 diabetes is essential to improve glycaemic control et reduce risk of diabetes complications. Key recommendations for people with diabetes are largely similar to those for the general population. Overweight or obese diabetic persons should be supported with evidence-based treatments to achieve and maintain weight loss. A wide range of carbohydrate intakes are acceptable and diets with a low glycaemic index or low glycaemic load may be recommended, provided their composition is consistent with overall diet recommendations for dietary fibers, sugars, saturated fats and proteins. It is also important to consume minimally processed plant foods, such as whole grains, vegetables, whole fruits, legumes, while reducing the consumption of red and processed meats, sodium and sugar-sweetened beverages.

La prise en charge nutritionnelle du diabète de type 2 est essentielle afin d'améliorer l'équilibre glycémique et réduire le risque de complications liées au diabète. Les principales recommandations diététiques pour les personnes diabétiques sont largement comparables à celles prodiguées dans la population générale. Les sujets diabétiques en surpoids ou obèses devraient bénéficier de prises en charge validées pour obtenir et maintenir une perte de poids. Un apport en glucides très variable est autorisé, avec des aliments à charge glycémique faible, et une composition adéquate en fibres, sucres, acides gras saturés et protéines. Il est important de réduire la consommation d'aliments transformés et de favoriser les céréales complètes, les produits végétaux (fruits et légumes), tout en limitant l'apport en viandes, sel et boissons sucrées.

Physical activity enhances the improvement of body mass index and metabolism by inulin: a multicenter randomized placebo-controlled trial performed in obese individuals.

BACKGROUND: Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention based on prebiotic supplementation can alter or even change the metabolic response to the prebiotic. We confirm in obese subjects and in high-fat diet fed mice that performing PA in parallel to a prebiotic supplementation is necessary to observe metabolic improvements upon inulin. METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants who received 16 g/day native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Primary outcomes concern the changes on the gut microbiota composition, and secondary outcomes are related to the measures of anthropometric and metabolic parameters, as well as the evaluation of PA. Among the 106 patients who completed the study, 61 patients filled a questionnaire for PA before and after intervention (placebo: n = 31, prebiotic: n = 30). Except the dietitian (who provided dietary advices and recipes book), all participants and research staff were blinded to the treatments and no advices related to PA were given to participants in order to change their habits. In parallel, a preclinical study was designed combining both inulin supplementation and voluntary exercise in a model of diet-induced obesity in mice. RESULTS: Obese subjects who increased PA during a 3 months intervention with inulin-enriched diet exhibited several clinical improvements such as reduced BMI (- 1.6 kg/m2), decreased liver enzymes and plasma cholesterol, and improved glucose tolerance. Interestingly, the regulations of Bifidobacterium, Dialister, and Catenibacterium genera by inulin were only significant when participants exercised more. In obese mice, we highlighted a greater gut fermentation of inulin and improved glucose homeostasis when PA is combined with prebiotics. CONCLUSION: We conclude that PA level is an important determinant of the success of a dietary intervention targeting the gut microbiota. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03852069 (February 22, 2019 retrospectively registered).

[Residual insulin secretion and management of type 1 diabetes: Interest of new C-peptide assays]. / Sécrétion résiduelle en insuline et traitement du diabète de type 1 - Intérêt des nouveaux dosages du peptide-C.

Plasma C-peptide represents a direct measure of endogenous insulin secretion. The development of new assays for measuring C-peptide have made it possible to demonstrate that a low insulin secretion persists in 30 to 80% of subjects with type 1 diabetes (T1D), even among those with long-standing disease. Several studies have established that the persistence of B cell function of the islets of Langerhans is associated with a protection against the development of microvascular complications and resulted in a significant reduction in the prevalence of severe hypoglycaemia in people with T1D. Further studies are needed to clarify the underlying pathophysiological mechanisms and the therapeutic strategies that would maintain B-cell function and thus improve the quality of life of patients with T1D.

Le peptide-C plasmatique constitue une mesure directe de la sécrétion endogène d'insuline. Le développement de nouveaux dosages du peptide-C a permis de démontrer qu'il persiste chez 30 à 80 % des sujets diabétiques de type 1 (DT1) une faible sécrétion d'insuline, même sur le long terme. Plusieurs études ont établi que la persistance de la fonction B des îlots de Langerhans était associée à une protection contre le développement des complications microvasculaires et engendrait une réduction significative de la prévalence des hypoglycémies sévères chez les personnes DT1. Mais des études complémentaires sont encore nécessaires afin de préciser les mécanismes physiopathologiques sous-jacents et les stratégies thérapeutiques qui permettraient de maintenir la fonction de la cellule B et d'améliorer ainsi la qualité de vie des sujets avec un DT1.

[Focus on tirzepatide, a dual unimolecular GIP-GLP-1 receptor agonist in type 2 diabetes]. / Focus sur le tirzépatide, un double agoniste unimoléculaire GIP-GLP-1 dans le diabète de type 2.

Tirzepatide is a unimolecular dual agonist of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, which is developed as once-weekly injection for the treatment of type 2 diabetes. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, basal insulin and two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protection (versus dulaglutide) is currently tested in SURPASS-CVOT. Finally, studies for the treatment of obesity and metabolic associated fatty liver disease are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except more diarrhoea.

Le tirzépatide est un agoniste unimoléculaire double des récepteurs du polypeptide insulinotrope dépendant du glucose (GIP) et du Glucagon-Like Peptide-1 (GLP-1) développé, en injection hebdomadaire, pour le traitement du diabète de type 2. De par la complémentarité des 2 incrétines, il a montré, de façon dose-dépendante (5, 10 et 15 mg), une efficacité supérieure (plus forte réduction du taux d'HbA1c (hémoglobine glyquée) et du poids corporel) par rapport au placebo, à l'insuline basale et à 2 analogues du GLP-1 (dulaglutide et sémaglutide) dans le programme SURPASS. Sa protection cardiovasculaire (versus le dulaglutide) est actuellement testée dans SURPASS-CVOT. Enfin, des études sont en cours dans l'obésité et la stéatopathie hépatique. La tolérance digestive du tirzépatide est comparable à celle des analogues du GLP-1, hormis davantage de diarrhée.

Prebiotic effect on mood in obese patients is determined by the initial gut microbiota composition: A randomized, controlled trial.

BACKGROUND AND AIMS: Metabolic and behavioural diseases, which are often related to obesity, have been associated to alterations of the gut microbiota considered as an interesting therapeutic target. We have analyzed in a cohort of obese patients treated with prebiotic inulin versus placebo the potential link between gut microbiota changes occurring upon intervention and their effect on psychological parameters (mood and cognition). METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 106 obese patients assigned to two groups: prebiotic versus placebo, who received respectively 16 g/d of native inulin or maltodextrin combined with dietary advice to consume inulin-rich or -poor vegetables for 3 months as well as to restrict caloric intake. Anthropometric measurements, food intake, psychological questionnaires, serum measures, and fecal microbiome sequencing were performed before and after the intervention. RESULTS: Inulin supplementation in obese subjects had moderate beneficial effect on emotional competence and cognitive flexibility. However, an exploratory analysis revealed that some patients exhibiting specific microbial signature -elevated Coprococcus levels at baseline- were more prone to benefit from prebiotic supplementation in terms of mood. Positive responders toward inulin intervention in term of mood also displayed worse metabolic and inflammatory profiles at baseline (increased levels of IL-8, insulin resistance and adiposity). CONCLUSION: This study shows that inulin intake can be helpful to improve mood in obese subjects exhibiting a specific microbial profile. The present work highlights some microbial, metabolic and inflammatory features (IL-8, insulin resistance) which can predict or mediate the beneficial effects of inulin on behaviour in obesity. Food4gut, clinicaltrial.gov: NCT03852069, https://clinicaltrials.gov/ct2/show/NCT03852069.

Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV.

BACKGROUND: As cardiovascular diseases represent the main cause of non-AIDS related death in people living with HIV (PLWH) with undetectable viral load, we evaluated lipid profile, weight gain and calculated cardiovascular risk change after switching from tenofovir disoproxil fumarate (TDF)-based regimens to tenofovir alafenamide (TAF)-based regimens. METHODS: For this retrospective study, we selected HIV-infected patients with suppressed viral load who fitted in one of the two groups below: First group (TDF/TDF): Patients treated continuously with TDF-based regimens. Second group (TDF/TAF): Patients treated with TDF-regimens during at least 6 months then switched to TAF-regimens while maintaining other drugs unchanged. Available data included date of birth, gender, ethnicity, lymphocyte T CD4+ count, weight, height, blood pressure, current/ex/non-smoker, diabetes mellitus, familial cardiovascular event, lipid profile, duration and nature of antiretroviral therapy. Lipid parameters, weight and calculated cardiovascular risk using 5-year reduced DAD score algorithm [Friis-Møller et al. in Eur J Cardiovasc Prev Rehabil 17:491-501, 2010] were analyzed in each groups. RESULTS: Switching from TDF to TAF resulted in a significant increase in triglycerides levels, total cholesterol and HDL cholesterol. LDL cholesterol and total cholesterol/HDL ratio did not show significant changes. Calculated cardiovascular risk increased after switch from TDF- to TAF-based therapy. CONCLUSIONS: Together with favorable outcomes at the bone and kidney levels, potential negative impact of TAF on lipid profile should be included in the reflection to propose the most appropriate and tailored ARV treatment.

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).

[Potential role of sacubitril/valsartan combination in type 2 diabetes]. / Intérêt de la combinaison sacubitril/valsartan dans le diabète de type 2.

Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI), is indicated for the treatment of heart failure with reduced ejection fraction. It has demonstrated benefits in terms of cardiovascular morbidity and mortality reduction in this population. Recently, this drug association has also been shown to improve glycemic control and insulin sensitivity in patients with obesity and/or type 2 diabetes. Furthermore, some studies suggest a protective role of this new drug class in diabetic nephropathy. Altogether, these data raise the question about the potential place of ARNI in prevention and treatment of type 2 diabetes, a condition closely associated with heart failure.

Le sacubitril/valsartan, premier médicament de la classe des ARNI (Angiotensin Receptor-Neprilysin Inhibitor), est indiqué dans le traitement de l'insuffisance cardiaque à fraction d'éjection réduite. Il a démontré des bénéfices en termes de réduction de morbimortalité cardiovasculaire dans cette population. Récemment, il a également été rapporté que cette association thérapeutique améliore le contrôle glycémique et la sensibilité à l'insuline des patients avec une obésité et/ou un diabète de type 2. De plus, certaines études suggèrent également un rôle protecteur de cette nouvelle classe médicamenteuse dans la néphropathie diabétique. Ces données soulèvent la question de la place éventuelle des ARNI dans la prévention et le traitement du diabète de type 2, une pathologie étroitement associée à l'insuffisance cardiaque.

[Potentiation of weight reduction with GLP-1 receptor agonists]. / Potentialiser la perte de poids avec les agonistes des récepteurs du GLP-1.

Glucagon-like peptide-1 receptor agonists are the antidiabetic agents that are associated with the greatest weight loss beyond a marked reduction in glycated haemoglobin. Weight loss results from a reduction in appetite through a predominant central effect combined with a peripheral effect. Liraglutide and semaglutide are developed for the treatment of obesity, independently of type 2 diabetes. Three approaches may be considered to potentiate weight loss: an increase of the drug dosage because of the demonstration of a dose-response, an add-on therapy with a sodium-glucose cotransporter type 2 inhibitor as this agent exerts a complementary action through urinary calorie loss (glucosuria) or a combination of the effects of two incretin hormones (GLP-1 and GIP), as the potent dual agonist tirzepatide currently in development.

Les agonistes des récepteurs du glucagon-like peptide-1 (GLP-1) sont les agents antidiabétiques qui, outre une baisse importante du taux d'hémoglobine glyquée, offrent la perte pondérale la plus marquée, en augmentant la satiété par un effet central, prédominant et périphérique. Le liraglutide et le sémaglutide sont développés pour le traitement de l'obésité, indépendamment de la présence d'un diabète de type 2. Trois approches sont possibles pour potentialiser la perte de poids: augmenter la posologie, compte tenu de l'existence d'une relation dose-réponse, ajouter un inhibiteur des sodium-glucose cotransporteurs 2 qui exerce un effet complémentaire grâce à une fuite calorique urinaire (glucosurie), ou encore combiner les effets de deux hormones incrétines (GLP-1 et Glucose-dependent Insulin Releasing Polypeptide), comme avec le puissant double agoniste tirzépatide en développement.

[Cardiovascular risk and type 1 diabetes]. / Risque cardiovasculaire et diabète de type 1.

People with diabetes are considered to have an increased cardiovascular risk. Patients with type 1 diabetes (T1D) generally have a cardiovascular risk profile that is different from those with type 2 diabetes. For this reason, we wanted to assess whether a population of T1D designed to be at very high cardiovascular risk achieved the strict goals recommended by the European Society of Cardiology. This is a descriptive cross-sectional analysis of a cohort of patients with T1D for at least 20 years followed at the University Hospital of Liege and considered to be at very high cardiovascular risk. We then discuss the relevance of strict targets in such patients by comparing them to different scientific societies. Finally, we briefly discuss the potential mechanisms by which T1D present an increased cardiovascular risk.

Les personnes diabétiques sont considérées comme ayant un risque cardiovasculaire accru. Les patients diabétiques de type 1 (DT1) ont un profil de risque cardiovasculaire souvent différent de celui des diabétiques de type 2. Nous avons évalué si une population de patients DT1, dits « à très haut risque cardiovasculaire ¼, atteignait les objectifs stricts recommandés par la Société européenne de cardiologie. Il s'agit d'une analyse transversale descriptive d'une cohorte de patients avec au moins 20 ans de DT1, suivis au CHU de Liège et considérés comme à très haut risque cardiovasculaire. Nous discutons de la pertinence de tels objectifs chez de tels patients, en les comparant à ceux de différentes sociétés savantes. Nous abordons brièvement les mécanismes potentiels à l'origine, dans ce groupe, d'un risque cardiovasculaire accru.

Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients.

OBJECTIVE: The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin. DESIGN: The stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice (hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3 months. RESULTS: We show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansia, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin. CONCLUSION: These findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders.

[Management of patients with type 2 diabetes at cardiovascular and renal risk†: ESC versus ADA-EASD]. / Traitement des patients diabétiques de type 2 à risque cardio-rénal†: ESC versus ADA-EASD.

Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors (gliflozins), which demonstrated a cardiovascular and renal protection, have profoundly changed the management of patients with type 2 diabetes who are at cardiovascular risk. Nowadays, these antidiabetic medications occupy a preferred position, independently of glucose control. This has been emphasized in the last guidelines of the European Society of Cardiology (ESC) and the joint consensus by the American Diabetes Association and the European Association for the Study of Diabetes (ADA-EASD), both published in 2020. Nevertheless, there are some discrepancies between the two points of view, especially concerning the definition of the patient at cardiovascular risk in primary prevention and the first-choice place still to be reserved to metformin in these patients.

Les agonistes des récepteurs du glucagon-like peptide-1 (GLP-1) et les inhibiteurs des cotransporteurs sodium-glucose de type 2 (SGLT2) (gliflozines), en démontrant une protection cardiovasculaire (CV) et rénale, ont profondément modifié le traitement du patient diabétique de type 2 à risque CV, en occupant désormais une position privilégiée, indépendamment du contrôle glycémique. Cette stratégie est actée dans les dernières recommandations de l'European Society of Cardiology (ESC) et dans la position conjointe de consensus de l'American Diabetes Association et de l'European Association for the Study of Diabetes (ADA-EASD), publiées en 2020. Il existe cependant certaines divergences entre les deux points de vue, notamment concernant la définition du patient à risque CV en prévention primaire et la place en première intention encore à réserver à la metformine.

[Strategies of home parenteral nutrition in adult patients in 2020]. / Stratégies de prise en charge de la nutrition parentérale au domicile du patient adulte en 2020.

Home parenteral nutrition (HPN) is increasingly used to allow patients to return home despite a partial or total dependency on artificial intravenous feeding. The follow-up, carried by a multidisciplinary team, is essential. The general practitioner (GP) is on the front line and establishes a network between the home nursing team and the hospital staff. The GP role is fundamental in the patients' daily clinical monitoring as well as in the early diagnosis of complications. Patients may need HPN for different pathologies, depending on these, the duration of the HPN may vary from a few months to several years. In this article, we will review the different practical modalities relating to the management of the HPN.

La nutrition parentérale à domicile (NPAD) est de plus en plus souvent utilisée afin de permettre aux patients un retour au domicile malgré une dépendance partielle ou totale à une alimentation artificielle intraveineuse. Un suivi par une équipe pluridisciplinaire est nécessaire. Le médecin de famille est en première ligne et fait le lien entre l'équipe infirmière au domicile et le personnel soignant hospitalier. Son rôle est primordial dans le suivi clinique du patient au quotidien ainsi que dans le diagnostic précoce des complications. Les patients peuvent nécessiter une NPAD pour différentes pathologies et, en fonction de celles-ci, sa durée peut varier de quelques mois à plusieurs années. Dans cet article, nous discuterons les différents points relatifs à la gestion et à l'organisation de la NPAD.