Introdução: Baixo nível de atividade física (AF) associado ao alto consumo energético contribuíram para transição nutricional no Brasil. Estilo de vida saudável reverte em benefícios cardiometabólicos. Considerando que estado inflamatório subclínico media os danos ao sistema cardiovascular, é possível que hábitos de vida saudáveis melhorem os fatores de risco, via atenuação da inflamação. Instrumentos padronizados para medir qualidade da dieta e AF estão disponíveis, mas não estudos locais avaliando a relação destes fatores entre si com base nestes instrumentos, ou examinando suas associações com estado inflamatório e perfil lipídico. Objetivos: Este estudo avaliou a associação entre a versão brasileira do Healthy Eating Index (B-HEI) e nível de AF e destes com marcadores inflamatórios, índice de resistência à insulina e variáveis lipídicas em indivíduos com alto risco cardiometabólico. Métodos: Nesta análise transversal foram incluídos 204 participantes (64,7 por cento mulheres; média de idade de 54,1 anos) de Estudo de Prevenção de Diabetes do CSEscola da FSP-USP, com pré-diabetes ou de síndrome metabólica sem diabetes. Foram realizados questionários e coletas de sangue. Foram utilizados três recordatórios alimentares de 24h para obtenção do B-HEI. O nível de AF foi medido pela versão longa do IPAQ, sendo determinada a AF no lazer, na locomoção, AF total e tempo de TV. Coeficiente de Spearman foi empregado para testar correlações. Para avaliar a relação entre o B-HEI e AF e dos tercis destas variáveis com marcadores inflamatórios e HOMA-IR foi usada ANOVA. Para avaliar associações independentes do B-HEI, tendo como variáveis dependentes parâmetros lipídicos, inflamatórios ou HOMA-IR, usou-se regressão linear múltipla e, para associações independentes da AF como as mesmas variáveis, usou-se regressão logística, sendo obtidos odds ratios (OR) e p de tendência. Resultados: Nos tercis do B-HEI, o nível de AF não diferiu; à medida que melhorava a qualidade da dieta houve tendência à redução do tempo de TV (21,4±11,6; 20,5±11,5; 16,8±10,4 h/sem; p=0,09). Na regressão linear, a circunferência abdominal associou-se inversamente aos escores de B-HEI, mantendo-se marginalmente significante após ajuste para idade e sexo. No mesmo modelo, proteína C reativa associou-se negativamente ao índice (p=0.02). Concentrações de adiponectina apresentaram significância marginal na análise sem ajustes (p=0.06). Estratificando-se indivíduos segundo a duração de AF na locomoção, lazer e total, indivíduos mais ativos (150 min/ sem) apresentaram menores medidas antropométricas, mas apenas para AF no lazer a tendência de redução foi significante. O perfil lipídico melhorou à medida que aumentou o nível de AF. Concentrações de interleucina-6 diminuíram com o aumento das durações de AF no lazer e total (p de tendência = 0,02 e 0,03, respectivamente), enquanto as de adiponectina tenderam a aumentar nos estratos mais ativos apenas para AF no lazer (p de tendência = 0,03). A tendência de hipercolesterolemia aumentou significantemente à medida que reduziu a duração de AF no lazer. Valores elevados da razão Apo B/Apo A foram inversamente associados com AF na locomoção, lazer e total. Foi observado aumento significante da OR de resistência à insulina entre categorias de AF no lazer (p de tendência = 0,04). Não foram observadas associações de qualquer domínio de AF com proteína C-reativa. Conclusões: Nossos dados não apoiam a hipótese de que boa qualidade da dieta e prática de AF estejam associadas. Reforçou-se a esperada associação de perfil cardiometabólico mais favorável com a prática de AF, mas não a da dieta de melhor qualidade medida pelo B-HEI / Background: Low physical activity (PA) level and high energy intake contributed to nutrition transition in Brazil. A healthy lifestyle reverts in cardiometabolic benefits. Considering that subclinical inflammatory status mediates damages to the cardiovascular system, healthy life habits may improve risk factors via attenuation of inflammation. Standardized tools to measure quality of diet and PA are available but not local studies assessing the relationship of these factors based on those tools, or examining their associations with inflammatory status and lipid profile. Objectives: This study evaluated the association between the Brazilian version of the Healthy Eating Index (B-HEI) and total, leisure and transportation PA level, and between those with inflammatory markers, insulin resistance index and lipids in individuals at high cardiometabolic risk. Methods: In this cross-sectional analysis, 204 participants (64.7 per cent women; mean age of 54.1 years) of the Study on Prevention of Diabetes from the FSP-USP School Health Center, with prediabetes or metabolic syndrome without diabetes were included. They were submitted to questionnaires and blood sample collections. 24-h food recalls were used to assess the B-HEI and PA was measured by the long version of the IPAQ. Spearman coefficient was employed to test correlations and ANOVA to analyze the association between the B-HEI and PA, and between the tertiles of these variables with inflammatory markers and HOMA-IR. Multiple linear regression was used to test independent associations of B-HEI, taking lipids, inflammatory markers and HOMA-IR as dependent variables. Logistic regression was used to test independent associations of PA with the same variables, and odds ratios (OR) and p for trend were obtained. Results: Across the B-HEI tertiles PA did not differ. However, as the quality of diet improves TV time decreases (21.4±11.6, 20.5±11.5, 16.8±10.4 h/week p=0.09). In linear regression analysis, abdominal circumference was inversely associated with BHEI, maintaining borderline significance after adjustment for age and sex. Creactive protein was shown to be inversely associated with the index (p=0.02). Adiponectin concentrations had borderline significance with B-HEI in crude analysis but not after adjustments (p=0.06). Stratifying according to the duration of transportation, leisure-time and total PA, the most active subset (150 min/week) showed lower anthropometric measurements, but only for leisure PA the tendency to decreasing values was significant. Lipid profile improved as PA levels increased. Interleukin-6 concentrations decreased as total and leisure PA increased (p for trend = 0.02 and 0.03, respectively), while adiponectin tended to increase in more active subsets only for PA at leisure time (p for trend = 0.03). Tendency for hypercholesterolemia increased significantly as leisure PA duration decreased. High Apo B/Apo A ratio was inversely associated with transportation, leisure and total PA. Significant increase in adjusted OR for insulin resistance from the category of highest to the lowest leisure PA was found (p for trend = 0.04) but statistical significance disappeared when adjusted for BMI. For increased C-reactive protein concentration, no significant association with any PA domain was observed. Conclusion: Our data do not support the hypothesis that good diet quality and PA practice were associated. The expected association of more favorable cardiometabolic profile with PA practice but not with better quality of diet was reinforced

Les antidépresseurs figurent parmi les médicaments les plus prescrits dans les pays industrialisés, incluant la France. L’utilisation croissante de ces médicaments dans la population générale suscite de multiples préoccupations quant à leurs effets indésirables sur la santé des populations. Plusieurs travaux de recherche se sont récemment intéressés à l’impact de l’utilisation prolongée de ces médicaments sur le risque cardiométabolique. Toutefois, les résultats produits sont contradictoires, limitées et ne concernaient pas la population Française. L’objectif général de ce travail de thèse consiste donc à étudier, à partir des données de deux grandes cohortes françaises (E3N et D.E.S.I.R.), l’association entre l’utilisation de médicaments antidépresseurs et le risque cardiométabolique, en essayant d’en comprendre les mécanismes sous-jacents. La première étude a montré que l’utilisation d’antidépresseurs était associée à un risque accru de diabète de type II. Cependant, l’association était évidente uniquement chez les femmes qui avaient plus de consultations médicales au cours des douze derniers mois. Les résultats de la seconde étude n’ont montré aucune association entre l’utilisation d’antidépresseurs et les marqueurs physio-biologiques qui caractérisent le diabète tels que : la glycémie à jeun, l’hémoglobine glyquée, la fonction des cellules β et la sensibilité à l’insuline. Enfin la troisième étude de ce travail de thèse a mis en évidence un risque accru de syndrome métabolique chez les utilisateurs d’antidépresseurs même si l’effet semblait se potentialiser chez les hommes uniquement. Les résultats de ces études apportent des éléments en faveur de l’hypothèse d’un biais de détection pour expliquer l’association observée entre utilisation d’antidépresseurs et diabète. Ce travail de thèse a permis de clarifier l’association entre l’utilisation d’antidépresseurs chez l’adulte et le risque cardiométabolique. Les implications scientifiques, cliniques et de santé publique sont discutées. / Antidepressants are among the most frequently prescribed medications in industrialized countries, including France. The increasing use of antidepressants in the general population has led to concerns about their adverse effects on health. Recently, important research work has focused on the impact of the prolonged use of antidepressants on cardiometabolic risk. However, the results produced were conflicting, limited and were not based on French population. The general objective of this thesis is therefore to study, based on data from two large French cohorts (E3N and D.E.S.I.R.), the association between the use of antidepressant drugs and cardiometabolic risk, with the ambition to understand the underlying mechanisms. The first study showed antidepressant medication use to be associated with an increased risk of type II diabetes. However, this association was evident only in women with more medical visits in the last twelve months. The results of the second study shows no association between antidepressant medication use and physio-biological markers that characterize diabetes such as fasting plasma glucose, glycated haemoglobin, β-cell function and insulin sensitivity. Finally, the third study showed an increased risk of metabolic syndrome among users of antidepressants, although the effect was apparent in men only. The results of these studies provide evidence supporting the hypothesis of a detection bias to explain the observed association between antidepressants use and diabetes. This work has helped to clarify the association between the use of antidepressants in adults and cardiometabolic risk. The scientific, clinical and public health implications are discussed.

No description available.

Gestational diabetes mellitus (GDM), a pregnancy-induced metabolic disorder that affects 2-10% of pregnancies poses future risk for diabetes mellitus (DM) and cardiovascular disease in mother and child. However, few prospective studies have examined the effect of GDM on altered maternal and cord blood lipids, specifically HDL, LDL, triglycerides, and total cholesterol, both during and after pregnancy. We have evaluated the association between GDM and lipid metabolism in pregnant mothers and their infants using data from a prospective cohort study conducted at Baystate Medical Center’s Wesson Women and Infant’s Unit. GDM was assessed prenatally by 3-hr GTT blood samples and was confirmed by obstetrician review. Lipids were assessed via fasting and non-fasting blood samples obtained during 3-hr GTTs performed at 24-28 weeks of gestation and 6-8 weeks post-partum. Data for covariates were collected via an interview form administered at the time of recruitment. We used multivariable linear regression to evaluate the association between GDM status and maternal lipids during and after pregnancy as well as cord lipids. These study results inform future research on GDM as a risk factor for future metabolic disorders in mother and child.

Background: A diet rich in vegetables, fruits, grains, fat-free or low-fat dairy, and proteins is known to have multiple beneficial health effects. However, a very limited number of studies have characterized food group intake and its association with cardiometabolic risk factors in Hispanic children. Objectives: The objectives of this study were to 1) assess food group intake in a sample of Hispanic children; and 2) examine the association between food group intake and overweight and elevated blood pressure in the same population. Methods: Data came from a pilot study of metabolic syndrome in Hispanic children. The study sample consisted of 116 2-to-10-year-old children receiving well-child care at a community health center in Johnson City, TN, from June 2015 to June 2016. Blood pressure, height and weight were measured using standard protocols. Food group intake was ascertained using the Block Kids Food Screener, a validated instrument. Child’s age, sex, and mother’s educational attainment were included as covariates. Binomial test of proportions was used to compare the study sample with the National Health and Nutrition Examination Survey (NHANES) gender-age group proportions not meeting recommended daily food group intake. Two sample t-test was used to examine differences in mean food intake by outcome variables of elevated blood pressure (>=90th percentile for age and sex) and being overweight (>85th percentile of the 2000 CDC growth charts). Multiple logistic regression was used to examine the association between food group intake and elevated blood pressure and being overweight while accounting for child's sex, age, and mother's educational attainment. Results: Hispanic children exceeded minimum fruit and legume national recommendations. Compared with the corresponding NHANES gender-age groups, a larger proportion of the sample met legume recommendations. However, similar proportions met fruit, vegetable, wholegrain, fiber and dairy recommendations. Children with elevated blood pressure ate less fruits, vegetables, and legumes than children with normal blood pressure. Legume intake (OR: 0.052, 95% CI: 0.04-0.64), dairy intake (OR: 0.61, 95% CI: 0.37-0.99), and fiber intake (OR: 0.88, 95% CI: 0.81-0.96) were protective against elevated blood pressure. In contrast, only fruit intake was protective against overweight (OR: 0.93, 95% CI: 0.87-0.99). Conclusion: Public health nutrition programs aimed at reducing the prevalence of overweight and elevated blood pressure in Hispanic children should consider supporting the intake of legumes, dairy, and fiber (for decreasing elevated blood pressure), and fruits (for reducing overweight).

Maternal obesity, physical inactivity, and negative perceptions of neighborhoods have been identified as obesogenic factors in older children; however, no study has explored this relationship in young Hispanic children. Furthermore, the relation between obesogenic maternal factors and blood pressure in Hispanic children has not been examined. Objectives: This study aimed to assess the association between Hispanic mother’s physical activity (PA) levels, body mass index (BMI), and PA-related perceptions of neighborhoods and their children’s PA, TV screen time, blood pressure (BP), and BMI. Methods: Data of 118 mother-child dyads enrolled in a cross-sectional study of metabolic syndrome in Hispanic children at a community health center in Johnson City, TN were used. Parent and child questionnaires were used to ascertain mother’s BMI, PA, perception of the safety and availability of PA amenities in their children’s neighborhoods, satisfaction with their children’s neighborhoods as a place to bring up children, and children’s PA and TV screen time. Children’s height, weight, and BP were measured. Multiple logistic regression was used to examine the association between child and maternal variables, adjusting for mother’s education and the child’s sex and age. Results: Children of obese mothers were more likely than children of mothers with normal BMI to engage in less than three days of at least 60 minutes of vigorous PA per week (OR: 6.47: 95% CI: 1.61-26.0). Children whose mothers did not engage in moderate PA were more likely to engage in less than three days of at least 60 minutes of vigorous PA per week (OR: 2.92, CI: 1.18-7.24); and have elevated BP (OR: 2.50, 95% CI: 1.02-4.53) than children whose mothers engaged in moderate PA. Conclusion: Our results suggest the need for interventions to help Hispanic mothers model physical activity and achieve and maintain healthy weight; if successful, these strategies could potentially influence their children’s blood pressure and physical activity levels.

<p>Diet is the number one leading modifiable cause of poor health globally, with poor diets accounting for 10.9 million (22%) of all deaths among adults in 2017. In addition, one of our generation’s forthcoming challenges is the rapid expansion of the population aged 60 years and older. Although people are living longer, there is an associated increase in the prevalence of aged-related chronic diseases and functional impairment, such as cardiometabolic diseases and sarcopenia. As such, dietary components can play a role in positively or negatively influencing the prevention and treatment of chronic cardiometabolic diseases and sarcopenia. One such dietary component is dietary protein, which is essential throughout the life course, from gestation through old age. Evidence supports dietary protein playing an important role in reducing the risk of developing age-related chronic diseases such as sarcopenia and cardiometabolic diseases. </p> <p><em><strong>     Study 1, Chapter 2:</strong></em> The Dietary Guidelines for Americans (DGA) recommends consuming a variety of “Protein Foods” based on “ounce equivalent” (oz-eq) portions. In addition, the 2020-2030 Strategic Plan for NIH Nutrition Research includes to “define the role of nutrition across the lifespan” with an objective to “assess the role of nutrition in older adults to promote healthy aging.” However, there is a paucity of primary research that directly compares EAAs bioavailability between young and older adults consuming the same oz-eq portions of varied Protein Foods. No study has assessed the same oz-eq portions of animal- versus plant-based Protein Foods on essential amino acids (EAAs) bioavailability for protein anabolism in young and older adults. Therefore, we conducted two sequential randomized, investigator-blinded, crossover, acute feeding trials with the same study design; first in a cohort of young adults and second in a cohort of older adults. The primary objective of this project was to assess the effect of consuming two oz-eq portions of animal-based (unprocessed lean pork or whole eggs) vs. plant-based (black beans or sliced almonds) Protein Foods as part of a mixed whole foods meal on plasma EAAs bioavailability for protein anabolism. Consistent with our hypotheses, participant age did not affect postprandial EAAs bioavailability, and consuming a meal with two oz-eq of unprocessed lean pork or whole eggs resulted in greater postprandial EAAs bioavailability compared to a meal with two oz-eq of black beans or raw sliced almonds in 1) young adults; 2) older adults; and 3) young and older adults combined. These findings show on the same oz-eq basis, consuming these animal- vs. plant-based Protein Foods more effectively provide bioavailable EAAs for protein anabolism. </p> <p><em><strong>     Study 2, Chapter 3:</strong></em> Poultry meat is the most consumed type of meat worldwide and in the US. Poultry is generally considered to be a “healthy” meat as it is a high-quality protein source and provides other essential nutrients. However, research assessing poultry and its effects on and relations with chronic diseases in humans is sparse, and the forms of poultry typically consumed in the US, are not necessarily in line with recommendations provided by the DGA. Therefore, we conducted a scoping review to systematically search and chronicle scientific literature pertinent to poultry intake and human health. Main findings from this project were 1) historically, little research, especially randomized diet-controlled feeding trials, has been conducted to understand associations between and effects of consuming poultry products on human health; 2) the majority of research is from observational studies assessing relationships between poultry intake and risks of morbidity and mortality from various types of cancer; 3) a paucity of research exists to support chicken as a health-promoting food in children; and 4) research taking into account poultry product processing and cooking methods is needed. Science and health professionals, the poultry industry, and the public will benefit from new observational and experimental research to address cutting-edge scientific, public policy, and consumer topics pertinent to poultry intake and human health. </p> <p><em><strong>     Study 3, Chapter 4:</strong></em> Emerging research on whey protein supplementation suggests it may be a potential modifier of type 2 diabetes mellitus (T2DM) risk factors, including glucose control. As systematic reviews and/or meta-analyses of randomized controlled trials are gaining importance in nutrition literature, we conducted an umbrella systematic review to search for and chronicle published systematic reviews and/or meta-analyses of randomized controlled trials pertinent to whey protein supplementation and T2DM modifiable risk factors (study 3, Chapter 4). Among the 13 systematic reviews, including 12 meta-analyses critically assessed for this umbrella review, no reviews reported any adverse effects of whey protein on any reported T2DM-related risk factor. Collectively, a preponderance of evidence indicates whey protein supplementation improves multiple clinical indicators of glucose control in apparently healthy adults and those at increased risk for type 2 diabetes mellitus. </p>

No description available.

Peripheral blood biomarkers can inform clinical care and drug development. Establishing causality between biomarker and disease is often critical for such applications, but epidemiological studies are limited due to biases from confounding and reverse causation. Mendelian randomization analysis leverages random inheritance of genetic variants at conception to mimic properties of randomized studies and estimate unconfounded effects between biomarker and disease, or vice-versa. This thesis demonstrates the utility of Mendelian randomization as a complementary tool to elucidate observational studies, predict drug safety and repurposing opportunities, and improve diagnostic biomarkers for cardiometabolic diseases. First, we characterized the hypothesized relationship between lipoprotein(a) and atrial fibrillation. We demonstrated both observed and genetically predicted lipoprotein(a) levels were associated with higher risk of atrial fibrillation across multiple independent cohorts. Importantly, risk was partly mediated independent of atherosclerotic cardiovascular disease, a known consequence of elevated lipoprotein(a) and itself a risk factor for atrial fibrillation. Next, we explored the lifelong effects of endogenous testosterone across a comprehensive set of 461 health outcomes in 161,268 males from the UK Biobank cohort. Using Mendelian randomization analysis, we found higher testosterone had beneficial effects on body composition and bone mineral density but adverse effects on prostate cancer, androgenic alopecia, spinal stenosis, and hypertension. Finally, we applied Mendelian randomization with the intention of discovering biomarkers caused by disease, which are expected to represent markers of early disease. As a proof-of-concept, we applied this framework to identify biomarkers associated with genetic predisposition to kidney function among 238 biomarkers measured in the ORIGIN trial. We discovered reduced kidney function caused increased trefoil factor 3 and showed its addition to models with known risk factors improved discrimination of incident early-stage chronic kidney disease. Taken together, Mendelian randomization identified biomarkers that warrant further study, with promising implications for screening, prevention, and treatment of different cardiometabolic diseases. / Thesis / Doctor of Philosophy (PhD) / Biological markers associated with disease can inform novel therapeutics or diagnostics but distinguishing causation from correlation is challenging. Mendelian randomization – a technique that leverages random inheritance of genetic variation to infer causality – was used to examine the role of biomarkers in cardiometabolic diseases. First, we implicated lipoprotein(a) as a risk factor for atrial fibrillation that acts independent of atherosclerotic cardiovascular disease. Second, we comprehensively characterized the lifelong effects of testosterone on health outcomes in males, where we found evidence of both beneficial and adverse effects on disease. Finally, we discovered trefoil factor 3 as a diagnostic marker for early-stage chronic kidney disease. Altogether, this thesis demonstrated different applications of Mendelian randomization that showcase its utility as a complementary tool to reveal causal biomarkers, and served to identify biomarkers for cardiometabolic diseases that merit further studies to evaluate their potential benefit on patient care.

<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>