<p>  To improve cardiometabolic health, omnivores are often recommended to simultaneously adopt a healthy dietary pattern with an emphasis on increasing intakes of plant-based proteins and decreasing intakes of red and processed meats. However, the totality of observational and experimental results inconsistently supports relations between red meat intake and risks of cardiometabolic diseases such as cardiovascular disease and type 2 diabetes mellitus. Red meat is often not clearly or consistently defined within nutrition and health research and is consumed within healthy and unhealthy dietary patterns. These issues contribute to the conflicting findings. Observational data, which assess red meat (both unprocessed and processed) within an unrestricted Western-style dietary pattern, typically support positive associations with cardiometabolic disease incidence and mortality outcomes. Whereas experimental randomized controlled trial data consistently show that consuming healthy dietary patterns with or without the inclusion of lean unprocessed red meat, improve cardiometabolic disease risk factors. These discordant findings have left laymen, researchers,and policymakers alike to question whether a high intake of red meat is causally related to cardiometabolic disease outcomes. The results of the single blinded crossover randomized controlled feeding trial (Study 1, Chapter 3) support that consuming a U.S.-style healthy dietary pattern that included two 3oz servings/day of lean unprocessed beef did not adversely affect cardiometabolic disease risk factors. Based on observational and experimental research, the umbrella systematic review described in Chapter4, led to the inference that red and processed meats are not causally related with cardiovascular disease. However, relations between processed meat and mixed unprocessed and processed meat and type 2 diabetes were inferred to be potentially causal. Overall, the results described in this dissertation support that lean and unprocessed red meats consumed within healthy dietary patterns do not adversely affect cardiometabolic health</p>

Background: Physical activity (PA) is an important component of a healthy pregnancy and has consistently been associated with improved weight management and a reduced risk of pregnancy complications. While the percentage of pregnant women meeting PA guidelines internationally is alarmingly low, no such data exists for the Canadian population. PA in pregnancy may also be a useful intervention for preventing and managing cardiometabolic dysfunction, but research in pregnancy is limited. Objectives: 1) To describe the PA and exercise habits of women in early pregnancy and assess the percentage of women meeting SOGC/CSEP guidelines for exercise in pregnancy; 2) To determine the association of PA with maternal cardiometabolic health in early pregnancy. Study Design: Maternal blood samples, and PA, dietary, and adiposity measures were collected from a subset of women in early pregnancy (12 – 17 wk gestation) upon enrollment in the Be Healthy in Pregnancy RCT. Fasted blood samples were analyzed for glucose, triglycerides, insulin, leptin, adiponectin and C-reactive protein (CRP). Self-reported and objectively measured PA were assessed using the PARmed-X for Pregnancy and an accelerometer. PA was quantified by three parameters: daily step count, energy expenditure (kcal/day) and meeting the SOGC/CSEP recommendations. Results: For the 198 participants of age 31 ± 4 years; BMI 25.4 ± 4.7kg/m2; at 13 ± 2 wk gestation (mean ± SD), 19.2% reported not exercising in early pregnancy. Approximately half of participants met the minimum SOGC/CSEP recommendation (15 min, 3x/wk), but only 14.2% met the preferred SOGC/CSEP recommendation (30 min, 4x/wk). Meeting the preferred recommendation was associated with lower CRP. Daily step count and energy expenditure (kcal/day) were not significantly associated with glucose, triglycerides, insulin, leptin, adiponectin or CRP. Percent body fat and a higher diet quality were associated with some of the cardiometabolic biomarkers. Conclusion: In a healthy pregnant cohort, while the majority had PA below recommendations, measured PA was not associated with most cardiometabolic biomarkers thus cardiometabolic risk in early pregnancy was low. / Thesis / Master of Science (MSc)

Je tiens à remercier les bourses des IRSC en collaboration avec le programme COPSE, les Bourses du Programme de Sciences biomédicales 2014-2015 et les Bourses d’excellence de la Faculté des études supérieures et post-doctorales Hydro-Québec (2015- 2016) pour leur contribution. / Introduction. Avec l’optimisation des traitements, le taux de guérison de la leucémie lymphoblastique aigüe (LLA) de l’enfant approche 90%. Cependant, 60% des survivants devront faire face à des complications à long-terme en lien avec les traitements. Ces patients ont un risque accru de complications cardiométaboliques telles que l’obésité, la résistance à l’insuline, la dyslipidémie et l’hypertension artérielle. Alors qu’il est reconnu que des facteurs génétiques contribuent au développement de ces complications, peu d’études ont observé l’impact de ces déterminants chez les survivants. Le but de cette étude est d’évaluer les associations entre les variantes rares et communes et le développement des complications cardiométaboliques chez les survivants de la LLA. Méthodes. La caractérisation du profil cardiométabolique et le séquençage de l’exome ont été réalisés dans une cohorte de 209 survivants de la LLA pédiatrique. Les variantes associées avec les complications cardiométaboliques ont été identifiées avec PLINK (commune) ou SKAT (rare et commune) et une régression logistique a été utilisée pour évaluer leur impact dans des modèles multivariés. Résultats. Nos analyses ont démontré que des variantes rares et communes dans les gènes BAD et FCRL3 sont associées au risque de présenter un phénotype dit extrême, soit trois facteurs de risque cardiométabolique et plus. Les variantes communes dans OGFOD3 et APOB et les variantes rares et communes dans BAD ont été associées à la dyslipidémie. Les variantes communes dans BAD et SERPINA6 ont été associées respectivement à l’obésité et la résistance à l’insuline. Conclusion. Notre étude a révélé une susceptibilité génétique au développement des complications cardiométaboliques chez les survivants de la LLA pédiatrique. Ces biomarqueurs pourront être utilisés pour la détection précoce et l’intervention chez cette population à haut risque. / Background. While cure rates for childhood acute lymphoblastic leukemia (cALL) now exceed 80%, over 60% of survivors will face treatment-related long-term sequelae, including cardiometabolic complications such as obesity, insulin resistance, dyslipidemia and hypertension. Although genetic susceptibility contributes to the development of these problems, there are very few studies that have so far addressed this issue in a cALL survivorship context. In this study, we aimed at evaluating the associations between common and rare genetic variants and long-term cardiometabolic complications in survivors of cALL. Method. We examined the cardiometabolic profile and performed whole-exome sequencing in 209 cALL survivors from the PETALE cohort. Variants associated with cardiometabolic outcomes were identified using PLINK (common) or SKAT (common and rare) and a logistic regression was used to evaluate their impact in multivariate models. Results. Our results showed that rare and common variants in the BAD and FCRL3 genes were associated (p<0.05) with an extreme cardiometabolic phenotype (3 or more cardiometabolic risk factors). Common variants in OGFOD3 and APOB as well as rare and common BAD variants were significantly (p<0.05) associated with dyslipidemia. Common BAD and SERPINA6 variants were associated (p<0.05) with obesity and insulin resistance, respectively. Conclusion. In summary, we identified genetic susceptibility loci as contributing factors to the development of late treatment-related cardiometabolic complications in cALL survivors. These biomarkers could be used as early detection strategies to identify susceptible individuals and implement appropriate measures and follow-up to prevent the development of risk factors in this high-risk population.

Le risque cardiométabolique (RCM) représente l’ensemble de tous les facteurs de risque pour les maladies cardiovasculaires et le diabète de type 2, incluant les facteurs de risque traditionnels et ceux émergents. Les évidences indiquent que la résistance à l’insuline, l’inflammation et le stress oxydant jouent un rôle clé dans le RCM, bien que l’acteur initiateur des altérations métaboliques caractéristiques du RCM reste encore à définir. Les femmes post-ménopausées constituent un sous-groupe important de la population puisque le risque de complications cardiométaboliques augmente après la ménopause. Les facteurs de RCM peuvent être modulés par l’alimentation, l’activité physique et la perte de poids. Alors que l’étude de nutriments / aliments spécifiques a permis de mieux comprendre l’implication de l’alimentation dans le RCM, celle de la qualité de l’alimentation est prometteuse. L’activité physique a des effets bénéfiques sur le RCM bien démontrés chez des personnes actives. Cependant, la relation entre la dépense énergétique et le RCM chez des individus sédentaires a été moins investiguée. De même, peu ou pas de données existent quant à une interaction synergique possible entre l’alimentation et l’activité physique sur le RCM. L’objectif de la présente thèse est d’investiguer les relations entre l’alimentation, l’activité physique, le stress oxydant et le RCM chez des femmes post-ménopausées en surpoids ou obèses, sédentaires et sans autres complications métaboliques. Les résultats montrent que d’une part, chez ces femmes sédentaires, une dépense énergétique active (DÉAP) élevée est associée à un meilleur profil inflammatoire, indépendamment de l’adiposité. D’autre part, il existe une relation synergique entre la qualité alimentaire et la DÉAP associée à un meilleur RCM. Une qualité alimentaire élevée combinée à une DÉAP élevée est associée à un meilleur profil lipidique et lipoprotéique et à une inflammation sub-clinique moindre, indépendamment de l’adiposité. Par ailleurs, dans une étude pilote, seuls des effets indépendants des changements de la qualité alimentaire et de la DÉAP sur les changements dans les facteurs de RCM ont été observés suite à cette diète hypocalorique de 6 mois, indépendamment du changement de l’adiposité encouru. En effet, au-delà de la réduction de l’adiposité et de l’amélioration du profil lipoprotéique induites par l’intervention, l’amélioration de la qualité alimentaire et de la DÉAP est associée, indépendamment l’une de l’autre, à une meilleure pression artérielle et un meilleur profil lipidique. Par ailleurs, une modification du système glutathion, un des systèmes antioxydants les plus communs de l’organisme, est associée à un RCM élevé. Une activité élevée de la glutathion peroxydase est associée à une résistance à l’insuline et à une épaisseur plus importante de l’intima-media de la carotide. Ces relations pourraient être médiées par un stress réducteur. En conclusion, l’adoption d’une saine alimentation et la pratique d’activités physiques doivent être encouragées dans les interventions visant à contrer l’obésité et ses complications, même en absence d’un changement d’adiposité. D’autre part, l’activité de la glutathion peroxydase pourrait être un paramètre impliqué dans le développement de désordres cardiométaboliques sub-cliniques et asymptomatiques chez des femmes obèses. D’autres investigations sont requises pour confirmer ces observations et élucider les mécanismes d’action impliqués. / The cardiometabolic risk represents all risk factors for cardiovascular diseases and type 2 diabetes, including the traditional and the emerging risk factors. Accumulating evidences indicate that insulin resistance, inflammation and oxidative stress are key players in the cardiometabolic risk, although the main cause initiating the metabolic alterations associated with the cardiometabolic risk has to be identified. Postmenopausal women are an important sub-group of the general population because the risk of developing cardiometabolic complications increases after menopause. The cardiometabolic risk factors can be modulated by dietary intake, physical activity and weight loss. Despite the fact that the study of specific nutrients or foods provided a better understanding of the implication of nutrition in the cardiometabolic risk, the relationship between diet quality and cardiometabolic risk has been less studied. Beneficial effects of physical activity on the cardiometabolic risk have been demonstrated in physically active individuals. However, the relationship between energy expenditure and the cardiometabolic risk in sedentary individuals has been less investigated. Similarly, it is unknown whether dietary intake interacts with physical activity in order to have greater beneficial effects on the cardiometabolic risk. The objective of this thesis is to determine the relationships between diet quality, physical activity and oxidative stress on the cardiometabolic risk in sedentary postmenopausal overweight and obese women without cardiometabolic complications. The results showed that, in these sedentary women, physical activity energy expenditure is associated with reduced inflammation, independently of adiposity. Moreover, there is a synergistic relationship between quality and physical activity energy expenditure (PAEE) which is associated with a reduced cardiometabolic risk compared to their separate effects. Indeed, high diet quality combined to high PAEE levels is associated with a better lipid and lipoprotein profile and a lower inflammatory status, independently of adiposity. However, in a pilot study, only independent effects of changes in diet quality and PAEE on the changes in cardiometabolic risk factors was observed following a 6-month hypocaloric diet. Indeed, beyond the reduction of adiposity and improvement of the lipoprotein profile induced by this diet, improved diet quality and increased PAEE are associated with beneficial changes in blood pressure and lipid profile. On the other hand, modification in the glutathione system, which is one of the most common antioxidant systems in the body, is associated with a higher cardiometabolic risk. Greater glutathione peroxidase activity is associated with insulin resistance and greater intima-media thickness of blood vessels. These relationships may be mediated through a reductive stress. In conclusion, a healthy diet and physical activity should be emphasized in interventions aimed to reduce obesity and its related complications, even in absence of change in adiposity. Moreover, glutathione peroxidase activity may be a parameter contributing to the development of sub-clinical but clinically relevant asymptomatic cardiometabolic abnormalities in obese women. Further investigations are needed to confirm these results and to elucidate the underlying mechanisms.

INTRODUCTION: Il existe peu d’évidences sur l’association entre le taux de chômage dans le milieu résidentiel (CR) et le risque de maladies cardiovasculaires parmi les résidents de milieux urbains. De plus, on ne sait pas si ce lien diffère entre les deux sexes. Cette thèse a pour objectif de déterminer la direction et la taille de l’association entre le CR et le risque de maladies cardiovasculaires, et d’examiner si cette association varie en fonction du sexe. MÉTHODES: Un sous-échantillon de 342 participants de l’Étude sur les habitudes de vie et la santé dans les quartiers montréalais a rapporté ses habitudes de vie et sa situation socio-économique. Des mesures biologiques et anthropométriques ont été recueillies par une infirmière. Le CR a été opérationnalisé en fonction d’une zone-tampon d’un rayon de 250 m centrée sur la résidence de chacun des participants à l’aide d’un Système d’Information Géographique (SIG). Des équations d’estimation généralisées ont été utilisées afin d’estimer l’association entre le CR et l’Indice de Masse Corporelle (IMC) et un score cumulatif de Risque Cardio-métabolique (RC) représentant la présence de valeurs élevées de cholestérol total, de triglycérides, de lipoprotéines de haute densité et d’hémoglobine glyquée. RÉSULTATS: Après ajustement pour l’âge, le sexe, le tabagisme, les comportements de santé et le statut socio-économique, le fait de vivre dans un endroit classé dans le 3e ou 4e quartile de CR était associé avec un IMC plus élevé (beta pour Q4 = 2.1 kg/m2, IC 95%: 1.02-3.20; beta pour Q3 = 1.5 kg/m2, IC 95%: 0.55-2.47) et un taux plus élevé de risque cardiovasculaires Risque Relatif [RR pour Q4 = 1.82 (IC 95 %: 1.35-2.44); RR pour Q3 = 1.66 (IC 95%: 1.33-2.06)] par rapport au 1er quartile. L'interaction entre le sexe et le CR révèle une différence absolue d’IMC de 1.99 kg/m2 (IC 95%: 0.00-4.01) et un risque supérieur (RR=1.39; IC 95%: 1.06-1.81) chez les femmes par rapport aux hommes. CONCLUSIONS: Le taux de chômage dans le milieux résidentiel est associé à un plus grand risque de maladies cardiovasculaires, mais cette association est plus prononcée chez les femmes. / INTRODUCTION: Little is known about whether area-level unemployment is independently associated with individual-level Cardiovascular Disease (CVD) in an urban setting. Furthermore, it is unclear whether this relationship differs by sex. This thesis examined the direction and magnitude of the association between area-level unemployment (ALU) and Body Mass Index (BMI) and a marker for CVD risk, and whether this association differs by sex. METHODS: A sample of 342 individuals from the Montreal Neighbourhood Survey of Lifestyle and Health (MNSLH) self-reported behavioural and socioeconomic information. A registered nurse collected biochemical and anthropometric data. ALU was operationalised within a 250 m radius buffer centered on individual residence using a Geographic Information System (GIS). Generalized Estimating Equations were used to determine if body mass index (BMI), and a cumulative score for total cardiometabolic risk (TCR) representing elevated values for total cholesterol, triglycerides, high-density lipoprotein cholesterol, and glycosylated hemoglobin, were associated with ALU. RESULTS: After adjustment for age, gender, smoking status, behavioural, and socioeconomic covariates, living in an area in the upper ALU quartiles was associated with an elevated BMI [Q4 beta = 2.1 kg/m2 (95% CI: 1.02-3.20)] and greater TCR [Q4 RR = 1.82 (95 % CI: 1.35-2.44); Q3 RR = 1.66 (95% CI: 1.33-2.06)] relative to the 1st quartile. Sex-by-ALU interaction revealed a 1.99 kg/m2 (95% CI: 0.00-4.01) difference in BMI and 1.39-fold (95% CI: 1.06-1.81) greater TCR Score for women compared to men. CONCLUSIONS: Area-level unemployment is associated with greater CVD risk in men and women but associations are stronger among women.

Ce travail financé par l'ACDI a été réalisé au Laboratoire TRANSNUT de l'Université de Montréal (Canada)en collaboration avec le Laboratoire National de Santé Publique (Burkina Faso) et HKI-Burkina Faso. / L’objectif de l’étude conduite à Ouagadougou était d’évaluer l’état nutritionnel et les habitudes de vie des écoliers ainsi que leurs pratiques alimentaires et certains déterminants, afin d’orienter puis plus tard d’évaluer une intervention nutritionnelle. L’étude a inclus 799 écoliers du cours moyen (âge moyen : 11,7 ± 1,4a) fréquentant 12 écoles privées ou publiques, urbaines ou péri-urbaines. Le poids, la taille, la tension artérielle et l’hémoglobine ont été mesurés et la thyroïde évaluée par palpation. Les lipides sanguins, la glycémie et le rétinol sérique ont été mesurés dans un sous-échantillon (N=208). Un questionnaire complété en classe portait sur la fréquence de consommation d’aliments « santé » (fruits, légumes, viande, poisson, légumineuses) et «superflus » (gâteaux, biscuits, bonbons, glaces, soda), les déterminants du comportement alimentaire ainsi que les pratiques d’hygiène et d’activité physique. Les signes carentiels étaient : une faible rétinolémie, l’anémie, la maigreur, le retard de croissance et le goitre. Les facteurs de risque cardio-métabolique (RCM) consistaient en une tension artérielle élevée, le surpoids/obésité, l’hyperglycémie et la dyslipidémie. Au moins une carence était présente chez 57% des participants. L’anémie (40,4%) et la carence en vitamine A (CVA) (38,7%) étaient fortement prévalentes. Le retard de croissance touchait 8,8% et la maigreur 13,7% des enfants. L’anémie (p=0,001) et la CVA (p<0.001) étaient significativement plus élevées dans les écoles publiques que privées. Aucun cas de goitre n’a été détecté. Le surpoids/obésité était rare (2,3%) . La maigreur et le retard de croissance étaient significativement plus élevés en milieu périurbain. Au moins un facteur de RCM était présent chez 36% des écoliers dont le principal était un taux de cholestérol-HDL-(HDL-C) bas (19,3%), suivi du cholestérol total et du LDL-C élevés (11,6% chacun) et la pression systolique élevée (9,7%). Le sexe féminin était indépendamment et positivement associé aux taux de lipides sanguins dont paradoxalement le HDL-C. L’IMC était indépendamment associé à une tension élevée. On observait que le double fardeau de la malnutrition (DFM) affectait 27,5% des participants. Le score de fréquence de consommation des aliments superflus était plus élevé que celui des aliments santé (p=0,001). Pendant la semaine précédant l’étude, 25 % des enfants n’avaient pas consommé de fruits, 20% pas de viande, 20% pas de légumineuses alors que 18,3% consommaient des glaces tous les jours. Les écoliers du privé consommaient plus fréquemment autant les aliments santé que superflus que ceux des écoles publiques. Les écoliers du milieu urbain avaient un score plus élevé de consommation des aliments superflus que ceux du milieu péri-urbain. La consommation des aliments santé ou superflus était essentiellement expliquée par le contrôle perçu, la disponibilité des produits ainsi que l’influence de la mère pour les aliments santé et l’influence des pairs pour les aliments superflus parmi les explications explorées. Cette étude a montré que les signes de carence nutritionnelle sont répandus et prédominent encore chez les écoliers du milieu urbain, mais aussi que la fréquence des marqueurs de risque cardiométabolique n’est pas négligeable. Des mesures préventives devraient être entreprises pour contrer tant les problèmes de carences que de surcharge. / The aim of this study carried out in Ouagadougou was to assess the nutritional status of schoolchildren and to assess their lifestyle practices as well as their food habits and determinants, for the guidance and evaluation of a nutrition intervention. The cross-sectional survey included 799 schoolchildren in 5th grade (mean age 11.7 ± 1.4y) attending 12 private or public, urban or peri-urban schools. Weight, height, blood pressure and haemoglobin were measured and thyroid palpation was performed. Fasting serum lipids, glycaemia and serum retinol were measured in a sub-sample (N=208). A questionnaire was filled in classroom to assess consumption frequency of ‘healthy’ foods (fruits, vegetables, meat, fish, legumes) and ‘unhealthy’ items (cakes, cookies, candies, ice, soda) and underlying factors as well as hygiene and physical activity practices. Deficiencies signs were: low serum retinol, anaemia, thinness, stunting and goitre whereas cardiometabolic risk factors (CRF) signs consisted of elevated blood pressure (BP), overweight/obesity, hyperglycaemia, and dysglyceamia. At least one malnutrition sign was found in 57% pupils. Anaemia (40.4 %) and vitamin A deficiency (VAD) (38.7 %) were highly prevalent. Stunting affected 8.8% of children while thinness affected 13.7 % of them. Anaemia (p = 0.001) and DVA (p < 0.001) were significantly higher in public than private schools. Goitre was not detected. Overweight/obesity was rare (2.3 %). Thinness and stunting were significantly higher in peri-urban compared to urban schools. At least one CRF was found in 36% schoolchildren. The main risk factors were low HDL-cholesterol (HDL-C) (19.3%) followed by high total cholesterol, high LDL-cholesterol (11.6% each) and elevated systolic blood pressure (9.7%). Being a girl was independently associated with increased serum lipids including HDL-C paradoxically. Body Mass Index was independently associated with increased BP. It was found that the double burden of malnutrition (DBM) affected 27.5% children. Consumption scores of unhealthy food were significantly higher than healthy foods’ (p= 0.001). During the week prior to the survey, 25% of children had eaten no fruit, 20% no meat, 20% no legume, while 18.3% ate ice pop every day. Compared to public-school pupils, those from private schools consumed both healthy and unhealthy items more frequently. Urban school children had significantly higher unhealthy food scores compared to peri-urban schools. Children’s healthy and unhealthy food consumption was primarily explained by perceived control and availability for both types of foods, and maternal reinforcement for healthy foods and peers’ reinforcement for consumption of unhealthy items among the investigated explanations. This study showed that malnutrition is widely prevalent in schoolchildren in cities, concurrently with a sizeable prevalence of cardiometabolic risk factors. Preventive measures should be tailored to prevent both dietary inadequacies and excess.

L’obésité est un problème de santé publique reconnu. Dans la dernière décennie l’obésité abdominale (OA) a été considérée comme une maladie métabolique qui contribue davantage au risque de diabète et de maladies cardiovasculaires que l’obésité générale définie par l’indice de masse corporelle. Toutefois, dans les populations d’origine africaine, la relation entre l’OA et les autres biomarqueurs de risque cardiométabolique (RCM) demeure obscure à cause du manque d’études chez ces populations et de l’absence de valeurs-seuils spécifiques pour juger d’une OA. Cette étude visait à comparer la prévalence des biomarqueurs de RCM (OA, hypertension artérielle, hyperglycémie, dyslipidémie, résistance à l'insuline et inflammation pré-clinique) chez les Béninois de Cotonou et les Haïtiens de Port-au-Prince (PAP), à étudier l’association de l’OA avec les autres biomarqueurs de RCM, à documenter le rôle du niveau socio-économique (NSE) et du mode de vie dans cette association et à ’identifier les indicateurs anthropométriques de l’OA -tour de taille (TT) et le ratio TT/hauteur (TT/H)- et les seuils qui prédisent le mieux le RCM à Cotonou et à PAP. Il s’est agi d’une analyse de données transversales chez 452 adultes (52 % hommes) apparemment en bonne santé, âgés de 25 à 60 ans, avec 200 sujets vivant à Cotonou (Bénin) et 252 sujets à PAP (Haïti). Les biomarqueurs de RCM considérés étaient : le syndrome métabolique (SMet) d’après les critères harmonisés de 2009 et ses composantes individuelles - une OA à partir d’un TT ≥ 94cm chez les hommes et ≥ 80cm chez les femmes, une hypertension, une dyslipidémie et une hyperglycémie; la résistance à l’insuline définie chez l’ensemble des sujets de l’étude à partir du 75e centile de l’Homeostasis Model Assessment (HOMA-IR); un ratio d’athérogénicité élevé (Cholestérol sérique total/HDL-Cholestérol); et l’inflammation pré-clinique mesurée à partir d’un niveau de protéine C-réactive ultrasensible (PCRus) entre 3 et 10 mg/l. Le ratio TT/H était aussi considéré pour définir l’OA à partir d’un seuil de 0,5. Les données sur les habitudes alimentaires, la consommation d’alcool, le tabagisme, les caractéristiques sociodémographiques et les conditions socio-économiques incluant le niveau d’éducation et un proxy du revenu (basé sur l’analyse par composante principale des biens et des possessions) ont été recueillies au moyen d’un questionnaire. Sur la base de données de fréquence de consommation d’aliments occidentaux, urbains et traditionnels, des schémas alimentaires des sujets de chaque ville ont été identifiés par analyse typologique. La validité et les valeurs-seuils de TT et du ratio TT/H prédictives du RCM ont été définies à partir des courbes ROC (Receiver Operating Characteristics). Le SMet était présent chez 21,5 % et 16,1 % des participants, respectivement à Cotonou et à PAP. La prévalence d’OA était élevée à Cotonou (52,5 %) qu’à PAP (36%), avec une prévalence plus élevée chez les femmes que chez les hommes. Le profil lipidique sérique était plus athérogène à PAP avec 89,3 % d’HDL-c bas à PAP contre 79,7 % à Cotonou et un ratio CT/HDL-c élevé de 73,4 % à PAP contre 42 % à Cotonou. Les valeurs-seuils spécifiques de TT et du TT/H étaient respectivement 94 cm et 0,59 chez les femmes et 80 cm et 0,50 chez les hommes. Les analyses multivariées de l’OA avec les biomarqueurs de RCM les plus fortement prévalents dans ces deux populations montraient que l’OA était associée à un risque accru de résistance à l’insuline, d’athérogénicité et de tension artérielle élevée et ceci, indépendamment des facteurs socio-économiques et du mode de vie. Deux schémas alimentaires ont émergé, transitionnel et traditionnel, dans chaque ville, mais ceux-ci ne se révélaient pas associés aux biomarqueurs de RCM bien qu’ils soient en lien avec les variables socio-économiques. La présente étude confirme la présence de plusieurs biomarqueurs de RCM chez des sujets apparemment sains. En outre, l’OA est un élément clé du RCM dans ces deux populations. Les seuils actuels de TT devraient être reconsidérés éventuellement à la lumière d’études de plus grande envergure, afin de mieux définir l’OA chez les Noirs africains ou d’origine africaine, ce qui permettra une surveillance épidémiologique plus adéquate des biomarqueurs de RCM. / Obesity is recognized as a major public health problem. In the last decade abdominal obesity (AO) was considered as a metabolic disorder which further contributes to the risk of diabetes and cardiovascular disease than the general obesity defined by body mass index. However, in African origin population groups, the relationship between AO and other cardiometabolic risk (CMR) biomarkers remained unclear because of the lack of studies in these population groups and the lack of specific cut-off values to define AO. This study aimed to compare the prevalence of CMR biomarkers (OA, hypertension, hyperglycemia, dyslipidemia, insulin resistance and subclinical inflammation) in Beninese from Cotonou and Haitians from Port-au-Prince (PAP), to assess the association between AO and other CMR biomarkers in relation to Cotonou and PAP participants’ socioeconomic and lifestyle parameters and to define anthropometric indicators of AO -waist circumference (WC) and waist-to-height ratio (WHtR)- and specific thresholds that best predict the CMR in both Cotonou and PAP. The cross-sectional study included 452 apparently healthy adults (52 % men), aged 25-60 years, 200 subjects from Cotonou (Benin) and 252 subjects from PAP (Haiti). The CMR biomarkers were: the metabolic syndrome (MetS) according to the harmonized criteria of 2009, its individual components - AO defined by a WC ≥ 94cm in men and ≥ 80 cm in women, hypertension, dyslipidemia and hyperglycemia - Insulin resistance was set at the 75th centile of Homeostasis Model Assessment (HOMA-IR) for the whole sample of subjects. High atherogenicity index (total serum cholesterol/HDL-Cholesterol), subclinical inflammation according to high-sensitivity C-reactive protein (hsCRP) concentration between 3 to 10 mg/L was also assessed. WHtR from a cut-off point of 0.5 was also considered to assess AO. Data on dietary habits, alcohol consumption, tobacco, sociodemographic and socioeconomic status, including education level and a proxy of income (based on principal component analysis of property and possessions) were documented by a questionnaire. Dietary patterns were generated from Western, urban and traditional food frequency in each city by cluster analysis. Receiver Operating Characteristic (ROC) curves were used to assess the performance of specific WC and WHtR cut-offs to predict the CMR. MetS was present in 21.5 % and 16.1 % of participants in Cotonou and PAP respectively. AO was higher in Cotonou (52.5 %) than in PAP (36 %) with higher prevalence in women than in men. The serum lipid profile was more atherogenic in PAP with 89.3 % of low HDL-C in PAP comparing to 79.7 % in Cotonou and high seum TC / HDL-C ratio of 73.4 % in PAP versus 42 % in Cotonou. The specific WC and WHtR cut-off values were respectively 94 cm and 0.59 in women and 80cm and 0.50 in men. Multivariate analysis of AO with the most prevalent CMR biomarkers in these two population groups showed that AO was associated with increased risk of insulin resistance, high atherogenic index and high blood pressure, irrespective of socioeconomic and lifestyle factors. Two dietary patterns were defined: transitional and traditional in each city, but these were not associated with the CMR biomarkers although they were related to socioeconomic variables. This study confirms the presence of several CMR biomarkers in apparently healthy subjects. Additionally, AO was a key element of the CMR in both population groups. However, current WC thresholds should be reconsidered in light of larger studies to better define AO among Black African groups, which will improve the epidemiological surveillance of the CMR biomarkers.

Introdução: Mudanças na alimentação e atividade física das populações elevaram a incidência de doenças crônicas não-transmissíveis associadas à adiposidade corporal. Este quadro contribui para mortalidade cardiovascular, motivando iniciativas em saúde pública visando à prevenção. Há evidências de que populações que consomem a dieta mediterrânea apresentam menor mortalidade por todas as causas, inclusive cardiovasculares. Os benefícios desta dieta, rica em fibras, gorduras insaturadas e polifenóis, parecem decorrer da atenuação da inflamação, envolvida na gênese de doenças cardiometabólicas. Objetivo: Este estudo investigou os efeitos da modificação de uma refeição diária, o desjejum, de forma a incluir alimentos mediterrâneos, sobre o metabolismo lipídico, glicídico, inflamação subclínica e expressão de genes inflamatórios. Métodos: Foi um ensaio clínico cruzado com duração total de 10 semanas, incluindo 80 adultos com excesso de peso, não-diabéticos. Os participantes passaram por 2 intervenções de 4 semanas no desjejum, com wash-out de 2 semanas entre elas. Os desjejuns, brasileiro e modificado, foram isocalóricos, diferindo quanto ao conteúdo de fibras e tipos de ácidos graxos. Antes e após cada intervenção foi realizado teste de sobrecarga de gorduras (FTT) com refeição rica em gorduras (saturadas e insaturadas MUFA e PUFA, dependendo da intervenção) e coletas sanguíneas seriadas até 240 minutos para determinação de glicose, insulina, lípides e marcadores inflamatórios. Foram também analisadas as expressões de genes inflamatórios, antes e após cada intervenção. Para comparar as respostas às intervenções foram usados teste t de Student ou os correspondentes não-paramétricos e ANOVA para medidas repetidas. Para as expressões dos genes foi utilizado o método delta ct e a expressão relativa calculada tendo como base valores de jejum e pré-intervenção. Valor de p <0,05 foi considerado significante. Resultados: No Artigo 1 (Modification in a single meal is sufficient to provoke benefits in inflammatory responses of individuals at low-tomoderate cardiometabolic risk), o FTT com desjejum brasileiro comparada ao modificado provocou maiores concentrações de IL-6 e IL-8, e esta resposta se acentuou após intervenção. As concentrações de selectina E, TNF-, IFN-, IL-10 e IL-17 se elevaram apenas após intervenção brasileira. No Artigo 2 (Inflammatory and metabolic response to dietary intervention differs among individuals at distinct cardiometabolic risk levels), a intervenção com desjejum modificado reduziu (p<0.05) a circunferência da cintura e pressão arterial e aumentou as concentrações de HDL. Indivíduos com síndrome metabólica melhoraram fatores clássicos (pressão arterial e glicemia, além de apolipoproteína B) após desjejum modificado, enquanto aqueles sem a síndrome melhoraram marcadores inflamatórios. O Artigo 3 (Comparison of inflammatory genes expression and their circulating products after short-term fatty acids interventions in humans) mostrou que o FTT com desjejum rico em gordura saturada induziu maior expressão pós-prandial de IL-1 quando comparado ao rico em insaturadas, antes e após as intervenções. Houve tendência à maior expressão de IFN- e IL-6 após intervenção com desjejum brasileiro. Na metanálise do Artigo 4 (Impact of the content of fatty acids of oral fat tolerance tests on postprandial triglyceridemia: systematic review and meta-analysis) foram incluídos 18 estudos buscando comparar as respostas dos triglicérides a ácidos graxos saturados e insaturados. Verificou-se que após 8 horas de refeição rica em MUFA há menor trigliceridemia. As menores concentrações observadas após ingestão de PUFA em relação à de saturados não atingiu significância. Conclusões: Pequenas modificações na dieta podem, em período relativamente curto, promover benefícios ao perfil de risco cardiometabólico. Tais benefícios foram evidentes em parâmetros clínicos habituais e reforçados pelos efeitos na expressão de genes inflamatórios e em marcadores circulantes. Vislumbra-se potencial de aceitação da introdução de componentes da dieta mediterrânea em população não-mediterrânea como a brasileira, o que poderia melhorar o perfil de risco cardiometabólico no longo prazo. / Introduction: Changes in dietary pattern and physical activity of populations have elevated the incidence of chronic non-communicable diseases associated with increased adiposity. Evidence has shown that populations consuming Mediterranean diets have lower mortality from all causes, including cardiovascular diseases. The benefits of this diet rich in fiber and unsaturated fats, derived in part on the effects of these nutrients on inflammatory condition that triggers cardiometabolic diseases. Objective: This study investigated the effects of changing a meal of Brazilian menu, the breakfast, in order to approximate it to the Mediterranean pattern on lipid and glucose metabolism, subclinical inflammation and also on the expression of inflammatory genes. Methods: This study was a crossover trial lasting a total of 10 weeks, including 80 overweight adults, nondiabetic without drug treatment for dyslipidemia. Participants who met the inclusion criteria underwent two 4-week interventions in breakfast, with wash-out of two weeks between them. The breakfasts (Brazilian and modified) were isocaloric, differing according to fiber and types of fatty acids contents. Before and after each intervention, fat tolerance tests with meals rich in fat (saturated and unsaturated depending on the intervention) were perfomed, with blood sample collections for glucose, insulin, lipids and inflammatory markers up to 240 minutes. Also, expression of inflammatory genes before and after each intervention was analyzed. To compare the acute and sub-acute responses to interventions were used Student t test or the corresponding nonparametric test and ANOVA for repeated measures. For expression of the genes, delta CT method was used and the relative expression calculated based on fasting and pre-intervention values. P value <0.05 was considered significant. Results: In Article 1 (Modification in a single meal is sufficient to provoke benefits in inflammatory responses of Individuals at low-to-moderate cardiometabolic risk), we observed higher IL-6 and IL- 8 concentrations after ingestion of the Brazilian FTT compared with the modified one, whose elevations were even more pronounced after the intervention period. Higher concentrations of E-selectin, TNF-, IFN-, IL-10 and IL-17 were found at fasting and in postprandial state only after the Brazilian intervention. In Article 2 (Inflammatory and metabolic response to dietary intervention Differs Among Individuals at distinct cardiometabolic risk levels), the intervention with the modified breakfast decreased waist circumference and blood pressure and increased the concentrations HDL (p <0.05). Participants with metabolic syndrome showed improvements in traditional risk factors (blood pressure and plasma glucose and apolipoprotein B) whit the modified breakfast, while those without the syndrome improved inflammatory markers. Article 3 (Comparison of inflammatory gene expression and their circulating products after short-term interventions fatty acids in humans) showed that the Brazilian FTT induced higher expression of IL-1 compared to the modified one, before and after the interventions. A tendency for higher postprandial expression of IFN- and increased IL-6 expression after intervention with Brazilian breakfast were also detected. In the meta-analysis of Article 4 (Impact of the content of fatty acids in oral fat tolerance tests on postprandial triglyceridemia: systematic review and metaanalysis) a total of 18 studies were included. When comparing the triglycerides responses to saturated and unsaturated fatty acids, lower areas under the curve with the meals rich in MUFA were observed. Postprandial triglyceridemia after PUFA was lower, but not significantly different from meals rich in saturated fat. Conclusions: Small changes in diet are able to induce benefits in cardiometabolic risk profile in a relatively short period. Such benefits are seen in routine clinical parameters, which are compatible with the favorable effects on the expression of inflammatory genes and circulating biomarkers. There is a potential acceptance of introducing components of the Mediterranean diet in non-Mediterranean populations like Brazil, which could improve the cardiometabolic risk profile in the long term.

O Diâmetro Abdominal Sagital (DAS) é uma medida antropométrica relacionada com a gordura visceral e empregada para avaliar a obesidade abdominal, uma variável associada à síndrome metabólica. Sua utilização é indicada na prática clínica para avaliação de risco cardiometabólico em adolescentes obesos. OBJETIVO: Verificar a concordância entre o DAS e a circunferência abdominal (CA) na avaliação da obesidade central e sua associação com os critérios da Síndrome Metabólica e HOMA-IR em adolescentes obesos. CASUÍSTICA E MÉTODOS: Estudo de corte transversal constituído por 83 adolescentes obesos entre 14 e 18 anos, (46 do sexo feminino e 37 do sexo masculino) matriculados no Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, nos ambulatórios das Unidades de Endocrinologia Pediátrica e de Adolescentes. Foram submetidos a avaliações antropométricas (IMC, Escore Z do IMC, percentual de gordura corporal, circunferência abdominal, diâmetro abdominal sagital), laboratoriais (HDL-c, triglicérides (TG), glicemia (GLIS) e insulina para o cálculo do HOMA-IR) e de pressão arterial sistólica (PAS) e diastólica (PAD), utilizadas para classificação dos critérios da SM. RESULTADOS: Todos os adolescentes apresentaram valores elevados de IMC (36,9±6,7 kg/m2), Z-IMC (+3,27±0,94) e 91,6% da casuística tiveram valores alterados no percentual de gordura corporal (41,4% para o grupo feminino e 36% para o grupo masculino), confirmando a obesidade grave do grupo. Considerando o percentil >=90 do Center for Disease Control and Prevention (CDC), no National Health and Nutrition Examination Survey (NHANES 2011-2014), 85,5% dos adolescentes apresentaram valores elevados de CA (117,7 ± 14,7) e 89,2% valores alterados no DAS (26,9±3,7). Quanto às variáveis laboratoriais, 32,5% dos pacientes apresentaram diminuição de HDL-c e níveis aumentados de: TG (10,8%); GLIS (3,6%); PAS (32,5%,); PAD (21,7%) e HOMA-IR (79,5%), considerando toda a amostra. De acordo com os critérios utilizados pelo International Diabetes Federation, 27,7% da casuística apresentou SM. O DAS demonstrou estar significantemente correlacionado com as variáveis PAS (r=0,489 p < 0,001), PAD(r=0,277 p 0,011) e HOMA-IR (r=0,462 p < 0,001) nos grupos geral, feminino, masculino, com e sem SM. A correlação encontrada entre as medidas do DAS e CA no grupo geral e feminino foi de r = 0,91 (p 0,000) e, no grupo masculino, de r = 0,93 (p 0,000). A concordância entre a CA e o DAS é significante (Kappa k = 0.511; p < 0,001). Nos grupos geral, feminino e masculino com SM, a concordância é mais expressiva (Kappa k = 1,00; p < 0,001.). Esses resultados mostram que os adolescentes apresentavam risco cardiometabólico aumentado e expressiva obesidade central, identificada pelo DAS e CA, apesar de 73,5% deles estarem medicados. O DAS oferece vantagem metodológica na sua mensuração. CONCLUSÕES: Nas condições deste estudo, conclui-se que: as medidas antropométricas CA e DAS se equivalem para o grupo de adolescentes avaliados na classificação da SM; O DAS é preditor de PAS, PAD e HOMA-IR e forte indicador de risco cardiometabólico em adolescentes obesos / The sagittal abdominal diameter (SAD) is an anthropometric measure related to visceral fat and used to evaluate abdominal obesity, a variable associated with the metabolic syndrome. Studies have suggested its employment in the clinical practice for estimating cardiometabolic risk of obese adolescents. OBJECTIVE: To verify the concordance between SAD and abdominal circumference in the assessment of central obesity and its association with the Metabolic Syndrome cluster and with HOMA-IR in obese adolescents. CASUISTICS AND METHODS: In a cross-sectional study, 83 obese adolescents between 14 and 18 years (46 females and 37males) with body mass index (BMI) of 36.9 ± 6.7 kg/m2, followed at the Pediatric Endocrinology Unit and at the Adolescent Unit of the Children\'s Institute, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo were submitted to anthropometric (BMI, BMI Z Score, body fat percentage, abdominal circumference, sagittal abdominal diameter), laboratory (HDL-c, triglycerides, glycemia and insulin for calculating HOMA-IR) and systolic and diastolic blood pressure assessments aimed for classification of metabolic syndrome. Previous consentment was given by all patients and their families. RESULTS: All adolescents presented elevated BMI and Z-BMI, and high body fat percentage was displayed by 91.6% of the patients (41.4% for the female group and 36% for the male group), confirming severe obesity. Considering the >= 90 percentile cut-off values as provided by the Anthropometric Reference Data for Children and Adults: United States 2011-2014 for abdominal circumference and SAD, 85.5% of the patients presented high abdominal circumference values (117.7±14.7) and 89.2% presented elevated values of SAD (26.9±3.7). With regard to laboratory variables, 32.5% of the patients displayed decreased HDL-c and increased values of: triglycerides (10.8%); glycemia (3.6%); systolic blood pressure (32.5%); diastolic blood pressure (21.7%) and HOMA-IR (79.5%). According to the criteria of the International Diabetes Federation (IDF), 27.7% of patients presented metabolic syndrome. SAD was significantly correlated with systolic (r=0.489 p < 0.001) and diastolic (r=0.277 p 0.011) blood pressures and HOMA-IR (r=0.462 p < 0.001) in the general, female and male groups, with and without metabolic syndrome. The correlation between SAD and abdominal circumference in the general and female groups was r = 0.91(p 0.000) and in the male group was r = 0.93 (p 0.000). The concordance between SAD and abdominal circumference was significant (Kappa coefficient k = 0.511; p < 0.001). In the general, male and female groups with metabolic syndrome, the concordance was more expressive (Kappa coefficient; k = 1.00 and p < 0.001). These results show that the adolescents presented increased cardiometabolic risk and significant central obesity identified by SAD and abdominal circumference although 73.5% of the studied patients were maintained under medication for clinical metabolic syndrome symptoms. SAD displayed methodological advantages concerning its measurement. CONCLUSIONS: Under the conditions of this study, it is concluded that: the anthropometric measurements of SAD and abdominal circumference are equivalent for metabolic syndrome classification of the studied adolescents; that SAD is a predictor of systolic and diastolic blood pressures and HOMA-IR and is a strong indicator of cardiometabolic risk in obese adolescents

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