Polluants organiques persistants et risque de diabète de type 2

Des études épidémiologiques transversales et quelques études prospectives en population générale semblent généralement mettre en évidence des associations entre polluants organiques persistants (POP) et diabète, mais le niveau de preuve est encore discuté, en raison de l’ampleur incertaine du risque et d’un mécanisme d’action qui reste à clarifier

Association between genetic obesity susceptibility and mother-reported eating behaviour in children up to 5 years.

BACKGROUND: Many genetic polymorphisms identified by genome-wide association studies for adult body mass index (BMI) have been suggested to regulate food intake. OBJECTIVE: The objective was to study the associations between a genetic obesity risk score, appetitive traits, and growth of children up to age 5 years, with a longitudinal design. METHODS: In 1142 children from the Etude des Déterminants pre et post natals de la santé de l'ENfant (EDEN) birth cohort, a combined obesity risk-allele score (BMI genetic risk score [GRS]) was related to appetitive traits (energy intake up to 12 mo, a single item on appetite from 4 mo to 3 y, a validated appetite score at 5 y) using Poisson regressions with robust standard errors. The potential mediation of appetitive traits on the association between BMI-GRS and growth was assessed by the Sobel test. RESULTS: Children with a high BMI-GRS were more likely to have high energy intake at 1 year and high appetite at 2 and 5 years. High energy intake in infancy and high appetite from 1 year were related to higher subsequent BMI. High 2-year appetite seemed to partially mediate the associations between BMI-GRS and BMI from 2 to 5 years (all P ≤ 0.05). CONCLUSIONS: Genetic susceptibility to childhood obesity seems to be partially explained by appetitive traits in infancy, followed by an early childhood rise in BMI.The EDEN study is supported by Fondation pour la Recherche Médicale (FRM), French Ministry of Research: Federative Research Institutes and Cohort Program, INSERM Human Nutrition National Research Program, and Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients [AFD]), French Ministry of Health, French Agency for Environment Security (AFSSET), French National Institute for Population Health Surveillance (InVS), Paris‐Sud University, French National Institute for Health Education (INPES), Nestlé, Mutuelle Générale de l'Education Nationale (MGEN), French‐speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM), National Agency for Research (ANR non‐thematic programme), and National Institute for Research in Public Health (IRESP: TGIR 2008 cohort in health programme). The genotyping was funded by a Collaborative Research Grant from the European Society for Paediatric Endocrinology. K.K.O. is supported by the Medical Research Council (unit program: MC_UU_12015/2)

A modified self‐controlled case series method for event‐dependent exposures and high event‐related mortality, with application to COVID‐19 vaccine safety

We propose a modified self‐controlled case series (SCCS) method to handle both event‐dependent exposures and high event‐related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID‐19 vaccines. Event‐dependence of vaccinations, and high event‐related mortality, are likely to arise in other SCCS studies of COVID‐19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death

Prenatal and postnatal exposure to persistent organic pollutants and Infant growth: A pooled analysis of seven european birth cohorts

Background: Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results: We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion: To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels

Croissances staturale et pondérale jusqu'à cinq ans : relations avec la composition corporelle et les paramètres cardiométaboliques à l’adolescence. Étude Fleurbaix Laventie Ville Santé II

Background: Obesity is considered as a major public health problem, because it is associated with many complications, its prevalence is increasing and it progressively affects younger subjects. Low birth weight has been consistently associated with increasing risk of cardiovascular diseases, but this association might be due to a rapid postnatal catch-up growth.Objective: To study associations between early height and weight growth velocity and cardiometabolic risk factors in adolescence, and the relationship between parental Body Mass Index (BMI) or height and their offspring’s weight or height growth velocity.Population and methods: Five hundred and twelve children aged 8 to 17 years included in the FLVS II study in 1999. Anthropometric, clinical and biological parameters were measured and weight and height measurements during infancy and childhood have been collected. It allowed us to model weight and height growth bet- ween birth and twelve years. Using Structural Equation Model multiple relationships between birth, infancy, childhood and adolescent variables were estimated.Results: 1. Prevalence of cardiometabolic risk factors were relatively low in this general population. However, their relationship between abdominal adiposity was very significant, especially in girls. 2. We have shown critical periods during infancy and early childhood associated with adolescent overweight and with increased fat mass: the first six months of life and a period beginning at about three years. 3. A low ponderal index at birth was associated with an higher blood pressure in adolescence, even after an adjustment for adolescent fat mass. In girls, a low weight growth velocity during the first months of life was associated with modification in lipids metabolism consistent with increased insulin resistance. 4. Weight and height growth velocities were associated to parental anthropometric parameters, with different contributions along infancy and childhood ; in particular, three month weight growth was preferentially associated with paternal BMI.Conclusion: These results, in the light of the literature, show the first years of life as an important period for fat mass and cardiometabolic risk development, but some periods of growth are probably more critical. Research should be focalise on genetic, environmental and behavioral determinants of these periods in the perspective of early prevention.Contexte: L’obésité est une pathologie qui préoccupe beaucoup actuellement, de part les nombreuses complications qui lui sont associées, le nombre de personnes qu’elle concerne et le fait qu’elle touche des populations de plus en plus jeunes. Naître avec un faible poids à la naissance est associé à une susceptibilité accrue aux maladies cardiovasculaires, un rattrapage pondéral postnatal rapide pourrait être responsable de cette association.Objectif: Étudier les relations entre la vitesse de croissance staturale et pondérale précoce et la présence de facteurs de risque cardiométabolique à l’adolescence, ainsi que le rôle de l’Indice de Masse Corporelle (IMC) et de la taille des parents sur la croissance staturo-pondérale de leur enfant.Population et méthodes: Cinq cent douze enfants âgés de 8 – 17 ans à l’entrée dans l’étude FLVS II, en 1999. Des paramètres anthropométriques et clinicobiologiques ont été mesurés et les données longitudinales de poids et de taille ont été relevées à partir des carnets de santé et d’une première phase de l’étude (FLVS I). L’évolution de leur croissance a ainsi pu être modélisée, et les vitesses de croissance estimées. L’utilisation de modèles à équations structurelles a permis l’étude des multiples associations entre les variables de naissance, d’enfance et d’adolescence.Résultats: 1. Les prévalences de facteurs de risque cardiométabolique étaient relativement modestes dans cette population générale. Toutefois, l’association de ces facteurs avec une répartition abdominale des graisses était très significative, en particulier chez les filles. 2. Il semble exister des périodes de susceptibilité durant l’enfance durant lesquelles le risque de surpoids — particulièrement par une augmentation de masse grasse — serait augmenté : les six premiers mois de vie et la période après trois ans. 3. Une faible corpulence à la naissance était associée, chez les garçons, à une augmentation de la pression artérielle à l’adolescence, même après prise en compte de la masse grasse à cet âge. Chez les filles, une faible croissance dans les premiers mois de vie était associée à une modification du métabolisme lipidique en faveur d’une insulinorésistance. 4. Les croissances du poids et de la taille étaient associées aux paramètres anthropométriques des parents, avec des contributions différentes au cours du temps ; en particulier, la croissance pondérale à trois mois était davantage associée à l’IMC paternel.Conclusion: Ces résultats, associés à ceux de la littérature, soulignent l’importance des premières années de vie dans le développement de la masse grasse et du risque cardiométabolique, avec toutefois l’existence de périodes de susceptibilité. La recherche doit maintenant se focaliser sur les d ́eterminants génétiques, environnementaux et comportementaux de ces différentes périodes

Relations entre la croissance dans la petite enfance et la survenue de surpoids et la répartition adipeuse à l'adolescence (résultats et hypothèses biologiques)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Croissances staturale et pondérale jusqu'à cinq ans (relations avec la composition corporelle et les paramètres cardiométaboliques à l'adolescence. Etude Fleurbaix Laventie Ville Santé II)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Perturbateurs endocriniens et croissance des enfants

According to the "environmental obesogen hypothesis", early-life (including in utero) exposure to endocrine disrupting chemicals (EDCs) may disturb the mechanisms involved in adipogenesis or energy storage, and thus may increase the susceptibility to overweight and obesity. Animal models have shown that exposure to several of these chemicals could induce adipogenesis and mechanisms have been described. Epidemiological studies are crucial to know whether this effect could also be observed in humans. We aimed at summarizing the literature in epidemiology on the relationship between EDCs exposure and child's growth. Overall, epidemiological studies suggest that pre- and/or early postnatal exposure to some EDCs may increase the risk of overweight or obesity during childhood. In that review, we present some limitations of these studies, mainly in exposure assessment, that currently prevent to conclude about causality. Recent advances in epidemiology should bring further knowledge.Selon l’hypothèse de l’existence d’obésogènes environnementaux, des expositions à des perturbateurs endocriniens (PE) pendant la périodeprécoce de vie (incluant la période intra-utérine) pourraient perturber les mécanismes impliqués dans l’adipogenèse et le stockage énergétique etainsi, augmenter la susceptibilité au surpoids et à l’obésité. Des modèles animaux ont montré que des expositions à plusieurs de ces chimiquespouvaient stimuler l’adipogenèse et des mécanismes ont été décrits. Les études épidémiologiques sont essentielles pour savoir si cet effet estégalement observé chez l’homme. Nous avions pour objectif de résumer la littérature en épidémiologie sur la relation entre l’exposition à des PE etla croissance des enfants. Globalement, les études épidémiologiques suggèrent que certaines expositions pré- ou postnatales pourraient augmenterlerisque de surpoids ou d’obésité durant l’enfance. Dans cette revue, nous présentons également des limites de ces études, principalement concernantl’évaluation de l’exposition, qui empêchent pour le moment de conclure à la causalité de ces associations. Des avancées récentes en épidémiologiedevraient permettre d’améliorer la connaissance dans ce domain

Environmental contaminants and child’s growth

Experimental data have suggested that some contaminants in the environment may increase the risk of obesity. Infants can be exposed to chemicals either prenatally, by trans-placental passage of chemicals, or postnatally by their own diet and by other external pathways (air inhalation, dust, hand-to-mouth exposure) after birth. In order to provide a review of epidemiological evidence on the association between prenatal exposure to chemicals and prenatal and postnatal growth, we present the literature from systematic review articles and international meta-analyses, when available, or recent research articles when summarising articles were not available. The most studied contaminants in this field were persistent organic pollutants (e.g. organochlorinated pesticides, polychlorinated biphenyls, PCBs), non-persistent pollutants (e.g. phthalates, BPA), toxic heavy metals (i.e. cadmium, lead and mercury), arsenic, mycotoxins and acrylamide. Mounting evidence suggests that child’s growth may be associated with prenatal or postnatal exposures to environmental contaminants. Improving exposure assessment and studying the contaminants as mixtures should allow to gain knowledge about the environmental determinants of growth and obesity

N-nitrosodimethylamine-Contaminated Valsartan and Risk of Cancer: A Nationwide Study of 1.4 Million Valsartan Users

International audienceBACKGROUND: Since July 2018, numerous lots of valsartan have been found to be contaminated with N-nitrosodimethylamine (NDMA). We aimed to assess the association between exposure to valsartan products contaminated with NDMA and the risk of cancer. METHODS AND RESULTS: This study was based on data from the Système National des Données de Santé, which is a national database that includes all French residents’ health-related expenses. The target population was consumers of valsartan between January 1, 2013 and December 31, 2017, aged between 40 and 80 years old. The association of exposure to contaminated valsartan with the occurrence of any malignancy and cancer by location was evaluated by fitting Cox proportional hazards models weighted by the inverse probability of treatment. A total of 1.4 million subjects without any history of cancer were included. A total of 986 126 and 670 388 patients were exposed to NDMA-contaminated and uncontaminated valsartan, respectively. The use of the NDMA-contaminated valsartan did not increase the overall risk of cancer (adjusted hazard ratio [aHR], 0.99 [95% CI, 0.98–1.0]). However, exposed patients had a higher risk of liver cancer (aHR, 1.12 [95% CI, 1.04–1.22]) and melanoma (aHR, 1.10 [95% CI, 1.03–1.18]). We estimated a mean of 3.7 and 5.8 extra cases per year per 100 000 person-years of liver cancer and melanoma, respectively. CONCLUSIONS: Our study was the largest to date to examine cancer risks associated with exposure to NDMA-contaminated valsartan. Our findings suggest a slight increased risk of liver cancer and melanoma in patients exposed to NDMA in regularly taken medications