La dénutrition au CHU d'Angers : Analyse du codage de 2010 à 2012

La dénutrition est très fréquente chez les patients hospitalisés. Elle résulte d'un déséquilibre entre les apports et les besoins de l'organisme, engendrant une perte de masse tissulaire et des altérations fonctionnelles qui entrainent ou aggravent un grand nombre de pathologies. Son dépistage et sa prise en charge ont démontré leur efficacité et sont une priorité de santé publique. L'analyse du PMSI au CHU d'Angers de 2010 à 2012 .montre que le taux de prévalence du codage de la dénutrition n'est pas un bon indicateur du taux réel de dénutrition hospitalière, probablement en raison d un manque de dépistage mais aussi d'une sous déclaration relative. Le taux de codage semble peu influencé par le degré d'activité des diététiciens, sauf dans certains services où l échange entre médecins et diététicien est renforcé. Il existe d autre part grande hétérogénéité de taux de prévalence du codage de la dénutrition selon les services, reflétant probablement une disparité et une insuffisance de prise en compte des problématiques nutritionnelles.Malnutrition is common in hospitalized patients. It results from an imbalance between contributions and needs of the body, causing a loss of tissue mass and functional alterations that result or aggravate many illnesses. Its detection and treatment have proven effective and are a public health priority. PMSI analysis in the CHU of Angers from 2010 to 2012 shows that the prevalence of malnutrition coding is not a good indicator of the actual rate of hospital malnutrition, probably due to a lack of screening but also an underreporting. The coding rate seems little influenced by the degree of activity dieticians, except in certain services where the relationship between doctors and dietician is strengthened. Otherwise there are great heterogeneity of prevalence of malnutrition coding according to services, probably reflecting a disparity and a lack of consideration of nutritional issues.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity

Aims: Obesity is a primary contributor to acquired insulin resistance leading to the development of type 2 diabetes and cardiovascular alterations. The carnitine derivate, propionyl-L-carnitine (PLC), plays a key role in energy control. Our aim was to evaluate metabolic and cardiovascular effects of PLC in diet-induced obese mice. Methods: C57BL/6 mice were fed a high-fat diet for 9 weeks and then divided into two groups, receiving either free- (vehicle-HF) or PLC-supplemented water (200 mg/kg/day) during 4 additional weeks. Standard diet-fed animals were used as lean controls (vehicle-ST). Body weight and food intake were monitored. Glucose and insulin tolerance tests were assessed, as well as the HOMAIR, the serum lipid profile, the hepatic and muscular mitochondrial activity and the tissue nitric oxide (NO) liberation. Systolic blood pressure, cardiac and endothelial functions were also evaluated. Results: Vehicle-HF displayed a greater increase of body weight compared to vehicle-ST that was completely reversed by PLC treatment without affecting food intake. PLC improved the insulin-resistant state and reversed the increased total cholesterol but not the increase in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet. Vehicle-HF exhibited a reduced cardiac output/body weight ratio, endothelial dysfunction and tissue decrease of NO production, all of them being improved by PLC treatment. Finally, the decrease of hepatic mitochondrial activity by high-fat diet was reversed by PLC. Conclusions: Oral administration of PLC improves the insulin-resistant state developed by obese animals and decreases the cardiovascular risk associated to this metabolic alteration probably via correction of mitochondrial function

Yearly Incidence of Stroke and Bleeding in Atrial Fibrillation with Concomitant Hyperthyroidism: A National Discharge Database Study

Background: Hyperthyroidism is associated with atrial fibrillation (AF), and the latter is a major risk factor for stroke. Aim: We aimed to investigate the yearly incidence of stroke and bleeding in AF patients with and without concomitant hyperthyroidism from the French National Hospital Discharge Database. Methods: Admissions with AF between January 2010 and December 2019 were retrospectively identified and retrieved from the French national database. Incidence rates of ischaemic stroke and bleeding were compared in AF patients with and without concomitant hyperthyroidism. The associations of risk factors with ischaemic stroke were assessed by Cox regression. Results: Overall 2,421,087 AF patients, among whom 32,400 had concomitant hyperthyroidism were included in the study. During the follow-up (mean: 2.0 years, standard deviation SD: 2.2 years), the yearly incidence of ischaemic stroke was noted to be 2.6 (95% confidence interval CI: 2.5–2.8) in AF patients with concomitant hyperthyroidism, and 2.3 (95%CI: 2.3–2.4) in non-thyroid AF patients. Hyperthyroidism was noted as an independent risk factor for ischaemic stroke (adjusted hazard ratio aHR: 1.133, 95%CI: 1.080–1.189) overall, particularly within the first year of hyperthyroidism diagnosis (aHR 1.203, 95%CI 1.120–1.291), however, the association became non-significant in subsequent years (aHR 1.047, 95%CI 0.980–1.118). Major bleeding incidence was lower in the hyperthyroid AF group in comparison to the non-thyroid AF group (incidence ratio: 5.1 vs. 5.4%/year, p < 0.001). The predictive value of CHA(2)DS(2)VASc and HAS-BLED scores for ischaemic stroke and bleeding events, respectively, did not differ significantly between AF patients with or without concomitant hyperthyroidism. Conclusions: Hyperthyroidism seems to be an independent risk factor of ischaemic stroke in AF patients, particularly within the first year of hyperthyroidism diagnosis

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Régulation par l'insuline du transport du glucose dans l'adipocyte

L'insuline augmente le transport du glucose dans l'adipocyte par la translocation à la membrane plasmatique d'un transporteur du glucose, Glut4, appartenant à un groupe de vésicules spécialisées. A l'état de base, ces vésicules sont séquestrées en position peri-nucléaire par le réseau de microtubules. L'insuline stimule fortement la translocation des vésicules contenant Glut4 à la membrane plasmatique en utilisant une double voie de signalisation : la voie dépendante de la phosphatidylinositol 3-kinase et la voie dépendante de la TC-10-kinase. La PKB est une sérine-thréonine kinase indispensable à l'action de l'insuline sur Glut4. Notre hypothe se est que la PKB, en plus de son activation par l'insuline en position membranaire, joue également un rôle au niveau même des vésicules Glut4. En utilisant des techniques d'imagerie cellulaire avec la Green Fluorescent Protein, nous montrons que l'expression de forme négative de PKB au niveau des vésicules Glut4 inhibe leur translocation en réponse à l'insuline. L'expression d'un mutant constitutionnellement actif n'a aucun effet par lui-même mais n'altère pas la translocation induite par l'insuline. In vivo, nous observons dans le tissu adipeux de sujets diabétiques insulinorésistants, une diminution de l'expression du gène codant pour Glut4 à l'état de base, associé à un défaut de stimulation de son expression en réponse à l'insuline. Notre travail montre que le transport du glucose dans l'adipocyte est un processus finement régulé par l'insuline et que la PKB possède un rôle fondamental dans cette régulation. Les sujets présentant une résistance à l'action de l'insuline ont également une baisse d'expression de Glut4 dans le tissu adipeux dont les conséquences sur le métabolisme adipocytaire restent à déterminer.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Impact du FGF21, une hormone du métabolisme énergétique, sur la reproduction

International audienceObesity or insulin resistance are the major non-infectious diseases that continue to progress worldwide. They promote diabetes and cardiovascular diseases, but also lead to a decrease in fertility in both sexes. FGF21, discovered in the 2000s, is a hormone closely linked to the energy status and has the ability to decrease insulin resistance. Its action through the FGFR1c, 3c & 4 receptors modulates tissues involved in energy-related metabolism but also the brain and the gonads. Recent data favor a role of FGF21 in female and male fertility, but raise the question about the role of FGF21 on reproductive function. In this review, we have scanned the different FGF21 actions on the reproductive axis, suggesting a potential therapeutic role in case of infertility.L’obésité et l’insulinorésistance sont les principales maladies non infectieuses qui progressent le plus dans le monde. Elles favorisent l’hypertension, les maladies cardio-vasculaires, mais conduisent aussi à une chute de la fertilité dans les deux sexes. Le FGF21, découvert dans les années 2000, est lié au statut énergétique de l’organisme et améliore l’insulinorésistance. Via ses récepteurs (FGFR1c, 3c,et 4), il agit sur le foie et au niveau d'organes régulant le métabolisme glucido-lipidique, mais aussi sur le cerveau et les gonades. Des données récentes sont ainsi en faveur d’un rôle régulateur de FGF21 sur la fertilité, tant féminine que masculine. Mais quel rôle FGF21 peut-il jouer dans la reproduction ? Dans cette revue, nous avons examiné les différentes activités que présente cette hormone sur la reproduction, ouvrant la voie à une éventuelle utilisation thérapeutique en cas d’infertilité

Regulation of hepatic mitochondrial metabolism in response to a high fat diet: a longitudinal study in rats.

International audienceMitochondrial dysfunctions have been detected in non-alcoholic steatohepatitis, but less information exists regarding adaptation of mitochondrial function during the initiation of hepatic steatosis. This study aimed to determine in rat liver the sequence of mitochondrial and metabolic adaptations occurring during the first 8 weeks of a moderate high fat diet (HFD). Sprague-Dawley rats were fed a HFD during 2, 4, and 8 weeks. Mitochondrial oxygen consumption, respiratory chain complexes activity, and oxidative phosphorylation efficiency were assessed in isolated liver mitochondria. Gene expression related to fat metabolism and mitochondrial biogenesis were determined. Results were compared to data collected in a group of rats sacrificed before starting the HFD feeding. After 2 and 4 weeks of HFD, there was a development of fatty liver and a concomitant increase the expression of mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT) and peroxisome proliferator-activated receptor γ. Higher serum β-hydroxybutyrate levels and enhanced hepatic pyruvate dehydrogenase kinase 4 expression suggested increased fatty acid oxidation. However, mitochondrial respiration and respiratory chain activity were normal. After 8 weeks of HFD, lower accumulation of liver triglycerides was associated with reduced expression of mtGPAT. At this time, oxygen consumption with palmitoyl-L: -carnitine was decreased whereas oxidative phosphorylation efficiency (ATP/O) with succinate was enhanced. Hepatic levels of mtDNA were unchanged whatever the time points. This longitudinal study in rats fed a HFD showed that hepatic lipid homeostasis and mitochondrial function can adapt to face the increase in fatty acid availability

Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models

International audienceIt is well known that adipokines are endocrine factors that are mainly secreted by white adipose tissue. Their central role in energy metabolism is currently accepted. More recently, their involvement in fertility regulation and the development of some reproductive disorders has been suggested. Data concerning the role of leptin and adiponectin, the two most studied adipokines, in the control of the reproductive axis are consistent. In recent years, interest has grown about some novel adipokines, chemerin, visfatin, resistin and apelin, which have been found to be strongly associated with obesity and insulin-resistance. Here, we will review their expression and role in male and female reproduction in humans and animal models. According to accumulating evidence, they could regulate the secretion of GnRH (Gonadotropin-Releasing Hormone), gonadotropins and steroids. Furthermore, their expression and that of their receptors (if known), has been demonstrated in the human and animal hypothalamo-pituitary-gonadal axis. Like leptin and adiponectin, these novel adipokines could thus represent metabolic sensors that are able to regulate reproductive functions according to energy balance changes. Therefore, after investigating their role in normal fertility, we will also discuss their possible involvement in some reproductive troubles known to be associated with features of metabolic syndrome, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia and intra-uterine growth retardation in women, and sperm abnormalities and testicular pathologies in men

Dexamethasone impairs muscle energetics, studied by (31)P NMR, in rats.

The original publication is available at www.springerlink.comAIMS/HYPOTHESIS: Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure. METHODS: To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg(-1) day(-1) for 6 days), in vivo by (31)P NMR spectroscopy. Results were compared with control and pair-fed (PF) rats before and after overnight fasting. RESULTS: Dexamethasone treatment resulted in decreased phosphocreatine (PCr) concentration and PCr:ATP ratio, increased ADP concentration and higher PCr to gamma-ATP flux but no change in beta-ATP to beta-ADP flux in gastrocnemius muscle. Neither 4 days of food restriction (PF rats) nor 24 h fasting affected high-energy phosphate metabolism. In dexamethasone-treated rats, there was an increase in plasma insulin and non-esterified fatty acid concentration. CONCLUSIONS/INTERPRETATION: We conclude that dexamethasone treatment altered resting in vivo skeletal muscle energy metabolism, by decreasing oxidative phosphorylation, producing ATP at the expense of PCr

Metabolically 'extremely unhealthy' obese and non-obese patients with diabetes and the risk of cardiovascular events: a French nationwide cohort study.

BackgroundNon-obese patients with diabetes mellitus (DM) are becoming more prevalent, but their cardiovascular risk (CV) especially when accompanied with cardio-renal-metabolic co-morbidities (hypertension, chronic kidney disease, hyperlipidemia) is not well characterised. The aim of the study was to assess the CV risk among patients with DM in relation to obesity and cardio-renal-metabolic co-morbidities.Materials and methodsThis was a cohort study of all patients with DM without a history of major adverse cardiovascular event who were hospitalized for any reason in France in 2013 with at least 5 years of follow-up. They were categorized by the presence of obesity vs no obesity, as well as three cardio-renal-metabolic co-morbidities: hypertension, chronic kidney disease, hyperlipidemia. 'Extremely unhealthy' patients with DM were defined as those having all 3 co-morbidities.ResultsThere were 196,112 patients (mean age 65.7 (SD 13.7) years; 54.3% males) included into the analysis. During a mean follow-up of 4.69 ± 1.79 years, when adjusted for multiple covariates, the non-obese and 'extremely unhealthy' obese patients had the highest risk of CV death [aHR 1.40 (95% CI, 1.22-1.61) and 1.48 (95% CI, 1.25-1.75), respectively]. The 'extremely unhealthy' obese had the highest risk of MACE-HF [aHR 1.84 (95% CI, 1.72-1.97)] and new-onset AF [aHR 1.64 (95% CI, 1.47-1.83)].ConclusionBoth non-obese and obese patients with DM with associated cardio-renal-metabolic co-morbidities are an 'extremely unhealthy' phenotype with the highest risk of CV death and CV events