Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p

Déterminants génétiques et nutritionnels de l'homocystéine (études de populations et association avec les maladies cardiovasculaires)

Nous avons comparé l'association des allèles 677T et 1298C de MTHFR avec le statut en folates, dans des secteurs géographiques ayant des fréquences contrastées. Le Mexique et la Sicile avaient les niveaux en folates les plus élevés et l'Afrique le plus bas. Le Mexique avait la fréquence de l'allèle 677T la plus élevée et la plus basse influence du génotype 677TT sur l'homocystéine (Hcy), l'opposé étant observé en Afrique. Nos données étaient conformes à l'hypothèse d'une interaction gène-nutriment entre C677T et folates. L'Hcy est un facteur de risque pour la maladie coronaire (MC) et l'insuffisance cardiaque aiguë. Nous avons évalué son association avec la dysfonction systolique ventriculaire gauche chez 560 patients admis pour angiographie coronaire. L'Hcy était plus élevée chez les 138 patients avec fraction d'éjection ventriculaire gauche (FEVG) médiane et MTRR AA étaient deux facteurs prédictifs indépendants de la MC. Contrairement aux études du Nord de l'Europe, MTRR AA est un facteur de risque indépendant de l'Hcy et de la MC dans une population française non supplémentée.NANCY1-SCD Medecine (545472101) / SudocSudocFranceF

Effets sur le métabolisme énergétique mitochondrial myocardique et hépatique de la carence en donneurs de méthyles au cours de la gestation et de l'allaitement chez le raton

Au cours du développement, les modifications du métabolisme des monocarbones liées à une malnutrition peuvent être délétères autant pour la mère que pour le nouveau-né. De plus, les conséquences à long terme d'une carence en période gestationnelle et périnatale sont mal connues, notamment en ce qui concerne les pathologies cardiaques et hépatiques. Nous avons mis en oeuvre un modèle nutritionnel de rates adultes carencées en donneurs de groupements méthyles (vitamines B12, folates et choline) avant la gestation. Ces micronutriments participent à la régulation de différentes enzymes impliquées dans le métabolisme de l'homocystéine. Afin de se placer dans un contexte de physiopathologie, proche de la situation clinique évaluée, nous avons choisi d'alimenter les rates avec un régime carencé un mois avant la mise en accouplement et de poursuivre ce régime pendant la période d'allaitement. Nous avons évalué les répercussions métaboliques et fonctionnelles du régime sur les tissus myocardique et hépatique, chez le nouveau né à 21 jours. Nous avons étudié l'effet de cette carence en groupements méthyles sur le métabolisme énergétique lipidique et sur la carnitine. Conséquences de la carence au niveau myocardique : Le régime carencé en donneurs de méthyles induit une hypertrophie cardiaque avec une augmentation de l'épaisseur du myocarde et un agrandissement des cardiomyocytes. L'étude protéomique du myocarde et l'analyse des données par bioinformatique identifient PGC-1[alpha], PPAR[alpha] et ERR[alpha] comme principaux déterminants des variations d'expression des protéines du métabolisme oxydatif mitochondrial. Nous avons observé une diminution d'expression de PPAR[alpha] et ERR[alpha] et une inactivation de PGC1[alpha] par hypométhylation et hyperacétylation, en lien avec une diminution d'expression de PRMT1 et de SIRT1 et une augmentation de SAH. Conséquences de la carence au niveau du foie : La carence s'accompagne de l'apparition d'une stéatose hépatique microvésiculaire, avec une élévation des taux tissulaires de lipides et de triglycérides. De plus, nous avons observé une augmentation des marqueurs pro inflammatoires sans augmentation des marqueurs de fibrose. A cet égard, nos résultats ont montré qu'un déficit de synthèse de carnitine, impliquée dans la bêta-oxydation et le stockage des acides gras, jouerait un rôle déterminant dans la pathogenèse de la stéatose chez le nouveau-né. Il existe également une dérégulation du métabolisme oxydatif des acides gras, avec diminution d'activité des complexes I et II de la chaîne respiratoire, qui résulte d'une hypométhylation de PGC1 et d'une diminution d'expression de PPAR[alpha], ER[alpha] et ERR[alpha]. En conclusion, nos résultats montrent que la carence maternelle en donneurs de méthyles, induit des modifications sur la fonction de PGC-1[alpha]. Ces modifications sont associées à des altérations de l'oxydation des acides gras et sur la fonction mitochondriale pendant la période néonatale, ce qui entraîne l'accumulation de lipides dans les tissus myocardique et hépatique. Le lien entre la carence en donneurs de méthyles et l'altération de la méthylation de PGC-1[alpha] modifie les activités des enzymes impliquées dans la méthylation et l'acétylation de PGC-1. Ces enzymes sont aussi liées à des modifications épigénomiques qui modulent la fonction et l'expression des protéines. Nos résultats sont en accord avec les études de population de Barker et al, qui suggèrent que la nutrition maternelle pendant les étapes précoces de la vie est corrélée avec le risque de maladies cardio-vasculaires dans la vie adulte indépendamment des autres facteurs de risqueDuring development, changes in carbon metabolism related to malnutrition may be deleterious for both the mother and the newborn. In addition, long-term consequences of a methyl deficiency gestational and prenatal are poorly understood. We are particularly interested in studying these effects on the heart and liver. We have used a nutritional model of adult rats deficient in methyl donors (vitamin B12, folate and choline) before pregnancy. To be placed in a context of pathophysiology, close to the clinical situation, we chose to feed the rats with a methyl deficient diet one month before mating and continue this diet during the suckling period. We evaluated the metabolic and functional effects of this diet on myocardial and hepatic tissues, in the newborn pups in 21 days old. We studied the effects of methyl deficient diet on lipid and energy metabolism and carnitine. Consequences of the deficiency at the myocardial: The diet deficient in methyl donors induces cardiac hypertrophy with an increase in myocardial thickness and enlargement of cardiomyocytes. The proteomics analysis of the bioinformatics data identifies PGC-1[alpha], ERR[alpha] and PPAR[alpha] as major determinants of changes in protein expression of mitochondrial oxidative metabolism. We observed a decreased expression of PPAR[alpha] and ERR[alpha] and an inactivation of PGC1[alpha] by hypomethylation and hyperacetylation, in conjunction with a decrease in the expression of PRMT1 and SIRT1 and increased the level of SAH. Consequences of the deficiency at liver: Deficiency is accompanied by the appearance of microvesicular hepatic steatosis, with elevated tissue levels of lipids and triglycerides. Increase of inflammation was observed in this model with no changes in fibrosis score. In this respect, our results showed a deficiency of carnitine synthesis, involved in the beta-oxidation and storage of fatty acids, play a role in the pathogenesis of hepatic steatosis in the newborn. There is also a deregulation of the oxidative metabolism of fatty acids, with decreased activity of complex I and II of the respiratory chain, resulting in hypomethylation of PGC1 and decreased expression of PPAR[alpha], ER[alpha] and ERR[alpha]. In conclusion, our results show that maternal deprivation in methyl donors impaired the function of PGC-1[alpha]. These changes are associated with alterations in fatty acid oxidation and mitochondrial function during the neonatal period, with lipid accumulation in myocardial tissue and liver. The link between the methyl donor deficiency and impaired methylation of PGC-1[alpha] alters the activities of enzymes involved in methylation and acetylation of PGC-1[alpha]. These enzymes are also associated with epigenetic changes and the function and gene expression. Our results are consistent with population studies by Barker and colleagues, who suggest that maternal nutrition during early stages of life is correlated with the risk of cardiovascular disease in adult, independent of other risk factorsMETZ-SCD (574632105) / SudocNANCY1-Bib. numérique (543959902) / SudocNANCY2-Bibliotheque electronique (543959901) / SudocNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

Hypertrophie myocardique, risque vasculaire et métabolisme des monocarbones. Conséquences métaboliques et moléculaires dans un modèle de raton carencé en donneurs de méthyles, et chez le sujet âgé

La carence en donneurs de méthyle est assez fréquente dans la période périnatale et au cours du vieillissement. Les donneurs de méthyle alimentaires, l'acide folique et la vitamine B12, influencent la teneur cellulaire en S-adénosylméthionine et S-adénosylhomocystéine et en homocystéine. Le lien entre les donneurs de méthyle et le métabolisme énergétique n'est pas connu, en dépit de leur rôle dans les voies liées à l'épigénétique et la synthèse de molécules méthylées. Nous avons évalué les conséquences d'un régime alimentaire déficient donneur de méthyle, dans le myocarde des ratons au moment du sevrage, soumis à une carence durant la gestation et la lactation. Le régime carencé augmente l'homocystéine plasmatique et S-adénosylhomocystéine myocardique. Les résultats mettent en évidence une cardiomyopathie hypertrophique et un déficit global de l'oxydation des acides gras avec acylcarnitines plasmatiques. Les liens entre le métabolisme des mono-carbones, l'oxydation mitochondriale des acides gras et de cardiomyopathie ont été constatées par des corrélations entre l'homocystéine et les acylcarnitines et le peptide natriurétique de type B. La carence en donneurs de méthyl peut être une condition aggravante de la cardiomyopathie en altérant l'oxydation des acides gras à travers une expression modifiée de PPAR[alpha] et ERR[alpha] et un déséquilibre de l'acétylation / méthylation de PGC1[alpha]. Nous avons montré que l'Hcy et Apo A-I ont été deux facteurs métaboliques déterminants de l'ABI dans une population ambulatoire de volontaires âgés d'une région rurale de la Sicile. L'influence négative de l'Hcy sur Apo A-I et sur le métabolisme des HDL ouvre des nouvelles perspectives sur l'implication de l'Hcy dans la physiopathologie de l'athérothromboseThe deficiency in methyl donors is prevalent in the perinatal period of life and in aging. Dietary methyl donors, folate and vitamin B12, influence the cellular content in Sadenosylmethionine and S-adenosylhomocysteine and increases homocysteine. The link between methyl donors and energy metabolism is not known, despite their role in pathways related to epigenetics and synthesis of methylated molecules. We evaluated the consequences of a diet lacking methyl donors, in myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. The deficient diet increased plasma homocysteine and myocardium Sadenosylhomocysteine. The results evidenced a hypertrophic cardiomyopathy with a global deficit in fatty acid oxidation with increased plasma acylcarnitines. The links between one-carbone metabolism, mitochondrial fatty acid oxidation and cardiomyopathy were ascertained by correlations between hyperhomocysteinemia, short-, medium- and long-chain acylcarnitines, and type-B natriuretic peptide. Methyl donor deficiency may be an aggravating condition of cardiomyopathy by impairing fatty acid oxidation through altered expression of PPAR[alpha] and ERR[alpha] and imbalanced acetylation/methylation of PGC1[alpha]. Finally, in a clinical study we sshowed that the Hcy and Apo A-I were two metabolic factors that influence the anckle brachial index in an ambulatory aged Sicilian population. The influence of homocysteine on Apo A-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosisNANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism

International audienceSirtuin1 (Sirt1) has a NAD (+) binding domain and modulates the acetylation status of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and Fork Head Box O1 transcription factor (Foxo1) according to the nutritional status. Sirt1 is decreased in obese patients and increased in weight loss. Its decreased expression explains part of the pathomechanisms of the metabolic syndrome, diabetes mellitus type 2 (DT2), cardiovascular diseases and nonalcoholic liver disease. Sirt1 plays an important role in the differentiation of adipocytes and in insulin signaling regulated by Foxo1 and phosphatidylinositol 3'-kinase (PI3K) signaling. Its overexpression attenuates inflammation and macrophage infiltration induced by a high fat diet. Its decreased expression plays a prominent role in the heart, liver and brain of rat as manifestations of fetal programming produced by deficit in vitamin B12 and folate during pregnancy and lactation through imbalanced methylation/acetylation of PGC1α and altered expression and methylation of nuclear receptors. The decreased expression of Sirt1 produced by impaired cellular availability of vitamin B12 results from endoplasmic reticulum stress through subcellular mislocalization of ELAVL1/HuR protein that shuttles Sirt1 mRNA between the nucleus and cytoplasm. Preclinical and clinical studies of Sirt1 agonists have produced contrasted results in the treatment of the metabolic syndrome. A preclinical study has produced promising results in the treatment of inherited disorders of vitamin B12 metabolism

Déterminants génétiques, nutritionnels et métaboliques de l'asthme professionnel

L'asthme professionnel (AP) est la maladie respiratoire d'origine professionnelle la plus fréquente dans les pays industrialisés. Il s'agit d'une pathologie complexe dite multifactorielle mettant en jeu un grand nombre de facteurs de risques génétiques, constitutionnels, comportementaux et environnementaux. Sur le plan génétique, l'asthme professionnel représente un bon modèle pour l'étude de l'asthme chez l'adulte et les mécanismes d'interactions gène-gène-environnement masquant ou modulant l'effet de la génétique restent encore à élucider. Aucune étude épidémiologique sur l'asthme professionnel n'a examiné le rôle des facteurs génétiques à un stade très précoce de l'exposition aux allergènes et aux irritants aéroportés. Nous avons donc cherché dans un premier temps à évaluer le rôle de certains polymorphismes génétiques en rapport avec l'inflammation et l'allergie, à savoir les IL4RA, IL13, TNFa, IL1A et IL5, sur le déclin de la fonction pulmonaire, l'apparition d'une obstruction ou d'une hyperréactivité bronchiques et l'évolution du monoxyde d'azote exhalé (FeNO) chez 441 apprentis boulangers/pâtissiers et coiffeurs (étude MIBAP). Dans cette première partie nous observons des interactions entre IL13 R130Q/IL4RA S478P et IL13 R130Q//IL4RA Q551R et la diminution du volume expiratoire forcé ou de la capacité vitale forcée. Le génotype GG du TNFA-G308A a été trouvé associé à l'hyperréactivité bronchique dans l'ensemble de la population et chez les sujets non atopiques ; nous avons aussi observé que certaines interactions gène-gène étaient associées à une modification du FeNO au cours des deux années d'apprentissage. Dans un deuxième temps, des déterminants nutritionnels de l'asthme ont été explorés dans une population de jeunes travailleurs engagés dans ces métiers à risque depuis 3 à 10 ans (étude ABCD). Les apports en vitamines, principalement les vitamines A, C, E D, et en acides gras polyinsaturés omégas 3 et 6 ont été étudiés par questionnaire de fréquence, le diagnostic d'asthme professionnel étant réalisé au moyen d'une batterie d'outils (examen clinique, spirométrie et test de réversibilité d'une obstruction bronchique, mesure du FeNO et examen des taux sériques d'IgE spécifiques). Les résultats portant sur 31 cas d'asthme professionnel et 196 témoins montrent une différence en fonction de la filière : chez les boulangers-pâtissiers, aucun facteur nutritionnel n'est objectivé, contrairement au groupe des coiffeuses chez qui les asthmatiques présentent des apports plus élevés des vitamines A et D. Un déficit en B12 semble être un facteur de risque de survenue d'asthme professionnel et ce indépendamment de la filière. En revanche, aucune corrélation n'est trouvée avec les taux sériques de l'homocystéine et la vitamine B9. A travers ces études au sein de ces jeunes populations à risque, il ressort que l'expression de certains facteurs de risque de l'asthme professionnel sont modulables en fonction du type d'exposition. Des comportements alimentaires à l'environnement de travail, l'émergence d'une maladie telle que l'asthme professionnel fait appel à des facteurs multiples dont la plupart peuvent être contrôlés et limités par des mesures de prévention efficacesOccupational asthma (OA) is the occupational respiratory disease most common in industrialized countries. It is a multifactorial disease involving a large number of risk factors genetic, constitutional, behavioral and environmental. At the genetic level, occupational asthma is a good model for the study of adult asthma and the mechanisms of interaction gene-gene-environment masking or modulating effect of genetic remain to be elucidated. None epidemiological studies on occupational asthma have examined the role of genetic factors in a very early exposure to allergens and airborne irritants. We initially assess the role of genetic polymorphisms related to inflammation and allergy, namely IL4RA, IL13, TNF, IL1A and IL5, on the decline of lung function, bronchial hyperresponsiveness and increasing of exhaled nitric oxide (FeNO) in 441 apprentice bakers / pastry-makers and hairdressers (MIBAP study). In this first part we observed interactions between IL13 and IL13 R130Q R130Q/IL4RA S478P / / IL4RA Q551R and decreased forced expiratory volume or forced vital capacity. The GG genotype of TNFA-G308A was found associated with bronchial hyperreactivity in the general population and in non-atopic subjects, we also observed that some gene-gene interactions were associated with a change in the FeNO after two years of training. In a second time, nutritionals determinants of asthma were investigated in a population of young workers employed in these occupations at risk from 3 to 10 years (ABCD study). Intake of vitamins, especially vitamins A, C, E,D, and polyunsaturated fatty acids omega 3 and 6 were studied by frequency questionnaire, the diagnosis of occupational asthma is achieved through a battery of tools (review clinical spirometry and reversibility of bronchial obstruction, FeNO measurement and examination of serum specific IgE). The results on 31 cases of occupational asthma and 196 controls showed a difference in terms of the sector: among bakers, no nutritional factor is objectified, unlike the hairdresser's asthmatics that have higher intakes vitamins A and D. B12 deficiency appears to be a risk factor for onset of occupational asthma regardless of the sector. In contrast, no correlation was found with serum levels of homocysteine and vitamin B9. Through studies in these young people at risk, it appears that the expression of certain risk factors of occupational asthma is flexible, depending on the type of exposure. The emergence of a disease such as occupational asthma involves multiple factors, most of which can be controlled and limited by effective preventive measuresMETZ-SCD (574632105) / SudocNANCY1-Bib. numérique (543959902) / SudocNANCY2-Bibliotheque electronique (543959901) / SudocNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall

International audienceHomocysteine (Hcy) is a non-protein forming amino acid which is the direct metabolic precursor of methionine. Increased concentration of serum Hcy is considered a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature. Serum Hcy is associated with atherosclerosis, hypertension and aneurysms of the aorta in humans, though the precise mechanisms by which Hcy contributes to these conditions remain elusive. Results from clinical trials that successfully lowered serum Hcy without reducing features of vascular disease in cardiovascular patients have cast doubt on whether or not Hcy directly impacts the vasculature. However, studies in animals and in cell culture suggest that Hcy has a vast array of toxic effects on the vasculature, with demonstrated roles in endothelial dysfunction, medial remodeling and adventitial inflammation. It is hypothesized that rather than serum Hcy, tissue-bound Hcy and the incorporation of Hcy into proteins could underlie the toxic effects of Hcy on the vasculature. In this review, we present evidence for Hcy-associated vascular disease in humans, and we critically examine the possible mechanisms by which Hcy specifically impacts the endothelial, medial and adventitial layers of the arterial wall. Deciphering the mechanisms by which Hcy interacts with proteins in the arterial wall will allow for a better understanding of the pathomechanisms of hyperhomocysteinemia and will help to define a better means of prevention at the appropriate window of life

Prevalence of IgE against neuromuscular blocking agents in hairdressers and bakers

International audienceBackgroundAllergic IgE-mediated reactions to neuromuscular blocking agents (NMBAs) are the main cause of immediate hypersensitivity reactions in anaesthesia; their predominant occurrence in the absence of previous exposure to NMBAs suggests a risk related to environmental exposure.ObjectiveTo investigate the prevalence of specific IgE to quaternary ammonium ions in two populations professionally exposed to quaternary ammonium compounds, in the north-eastern France.MethodsThe study had a retrospective follow-up design whereby apprentices were assessed after their 2-year training period as apprentices. The professionally exposed hairdresser populations (n = 128) were compared with baker/pastry makers (n = 108) and ‘non-exposed’ matched control subjects (n = 379).ResultsWe observed a 4.6-fold higher frequency of positive IgE against quaternary ammonium ions in hairdressers (HD), compared with baker/pastry makers (BP) and control (C) groups. The competitive inhibition of quaternary ammonium Sepharose radioimmunoassay (QAS-IgE RIA) with succinylcholine was significantly higher in HD, compared with BP and C groups, with inhibition percentage of 66.2 ± 7.4, 39.7 ± 6.0 and 43.8 ± 9.9, respectively (P 100 kU/L were the two significant predictors of IgE-sensitization against quaternary ammonium ions in the multivariate analysis of a model that included age, sex, professional exposure, increased concentration of total IgE (IgE > 100 kU/L) and positive IgE against prevalent allergens (Phadiatop®; P = 0.019 and P = 0.001, respectively).Conclusion and Clinical RelevanceThe exposure to hairdressing professional occupational factors increases IgE-sensitization to NMBAs and quaternary ammonium ion compounds used in hairdressing. Besides the pholcodine hypothesis, our study suggests that repetitive exposure to quaternary ammonium compounds used in hairdressing is a risk factor for NMBAs sensitization

Myocardium proteome remodelling after nutritional deprivation of methyl donors

Methyl donor (MD: folate, vitamin B12 and choline) deficiency causes hyperhomocysteinemia, a risk factor for cardiovascular diseases. However, the mechanisms of the association between MD deficiency, hyperhomocysteinemia, and cardiomyopathy remain unclear. Therefore, we performed a proteomic analysis of myocardium of pups from rat dams fed a MD-depleted diet to understand the impact of MD deficiency on heart at the protein level. Two-dimension gel electrophoresis and mass spectrometry-based analyses allowed us to identify 39 proteins with significantly altered abundance in MD-deficient myocardium. Ingenuity Pathway Analysis showed that 87% of them fitted to a single protein network associated with developmental disorder, cellular compromise and lipid metabolism. Concurrently increased protein carbonylation, the major oxidative post-translational protein modification, could contribute to the decreased abundance of many myocardial proteins after MD deficiency. To decipher the effect of MD deficiency on the abundance of specific proteins identified in vivo, we developed an in vitro model using the cardiomyoblast cell line H9c2. After a 4-day exposure to a MD-deprived (vs. complete) medium, cells were deficient of folate and vitamin B12, and released abnormal amounts of homocysteine. Western blot analyses of pup myocardium and H9c2 cells yielded similar findings for several proteins. Of specific interest is the result showing increased and decreased abundances of prohibitin and a-crystallin B, respectively, which underlines mitochondrial injury and endoplasmic reticulum stress within MD deficiency. The in vitro findings validate the MD-deficient H9c2 cells as a relevant model for studying mechanisms of the early metabolic changes occurring in cardiac cells after MD deprivation

Medium term post-bariatric surgery deficit of vitamin B12 is predicted by deficit at time of surgery

International audienceBackgroundPatients with morbid obesity have a high risk of deficits in micronutrients, after bariatric surgery. The reasons why systematic use of multivitamin and trace element supplements cannot prevent all deficits are complex and should deserve more attention. Little is known about the influence of micronutrient deficits at surgery.AimThis present study aimed to explore the deficit in vitamin B12 vs other micronutrients during the follow-up of a French cohort of cases with bariatric surgery under systematic multivitamin/trace elements supplementation and to determine whether it was influenced by clinical, metabolic characteristics at surgery.MethodsWe prospectively enrolled obese patients with bariatric surgery (laparoscopic gastric bypass or laparoscopic sleeve gastrectomy) between 2013 and 2018 (OBESEPI/ALDEPI Cohort, NCT02663388). They received a daily multivitamin/micronutrients supplement. Follow-up data at 4 visits, 2, 12, 18 and 24 months after surgery, were collected.ResultsThe highest rate of deficits was observed at visit 1 for vitamin D (35.7%), iron (21.9%) and folate (10.2%). Except B12, the deficits of all micronutrients decreased in later visits. In contrast, cases with vitamin B12 deficit decreased from 13.5% at surgery to 2.0% at visit 1, and increased in later visits, with a maximum of 12.0% at visit 3. Vitamin B12 concentration at surgery was the single predictor of B12 deficit at visit 3. It was also associated with age, and APRI score, an index of nonalcoholic fatty liver disease (NAFLD), in multivariate analysis.ConclusionsThe failure of systematic supplementation with multivitamin/trace elements tablets to prevent specific deficits illustrates the need for adapted specific supplementations, in some cases. The worsening of B12 deficit rate in the 18–24 months follow-up depends in part to low B12 at time of surgery. A special consideration should be devoted to this subset of patients.The cohort study was registered at clinicaltrials.gov as NCT02663388