Role of fitness on health during aging

Introducción: Durante el envejecimiento concurren una serie de cambios bioquímicos y físicos afectando las principales funciones del cuerpo humano. Existe suficiente evidencia científica de que la inactividad física agrava el aumento de peso, tejido graso y la pérdida de masa muscular y que esto a su vez empeora la salud de los adultos mayores y por ende las funciones en la vida diaria. Sin embargo, se desconoce cuál es el papel que juega la condición física entre las comorbilidades comunes de los adultos mayores. Los trabajos presentados en esta Tesis Doctoral se basan en resultados obtenidos del análisis de la base de datos del Estudio Nacional de Salud, Bienestar y Envejecimiento, SABE Colombia 2015 Estudio 1: el objetivo fue conocer la prevalencia de probable sarcopenia de acuerdo a las actualizaciones del European Working Group on Sarcopenia in Older People 2 así como explorar los factores asociados. En los análisis se incluyeron 5237 hombres y mujerescolombianos de 60 años o más de edad. La prevalencia de probable sarcopenia fue de 46,5% (95% IC: 45,1 ─ 47,8). La inactividad física (OR = 1,35, 95% IC = 1,14 ─ 1,59), diabetes(OR = 1,32, 95% IC = 1,11 ─ 1,56) y artritis (OR = 1,44, 95% IC = 1,25 ─ 1,67), estaban estrechamente relacionadas con la probable sarcopenia. Estudio 2:el objetivo consistió en determinar si la velocidad de la marcha moderaba la asociación entre obesidad y dependencia funcional. Además, es examinó los umbrales de moderación de acuerdo con la técnica estadística de Johnson-Neyman. Participaron un total de 20,507 de adultos mayores colombianos. Los resultados indicaron que la velocidad de la marcha moderaba (β=0.081; 95% IC: 0,045 ─ 0,117) la asociación entre obesidad y dependencia funcional. Los umbrales por debajo del cual la velocidad de la marcha moderaba negativamente la asociación era de 1,06 m/s.Estudio 3:el objetivo fue determinar si el exceso de adiposidad central se relacionada con la dependencia funcional y también si esta asociación es moderada por la fuerza de prensión manual. Participaron en este estudio 4169 individuos mayores de 59 años. Los resultados destacaron el rol mediador de la fuerza de prensión manual sobre la relación Doctorado en Ciencias de la Salud Autor: Miguel Ángel Pérez Sousa 11 inversa exceso de adiposidad y dependencia funcional. Los umbrales arrojados por la técnica de Johnson-Neyman fueron de 0,35 kg/kg2 y de 0,62 kg/kg2. Estudio 4: el estudio tenía como objetivo conocer si la pérdida de fuerza muscular asociada al exceso de adiposidad central podría ser mediado por el nivel de glucosa en sangre. Participaron en el estudio un total de 1571 adultos mayores colombianos. Los resultados indicaron que la glucosa en sangre mediaba el efecto perjudicial de un exceso de adiposidad central sobre la fuerza muscular(β = -0.069, 95%IC = -0.082 − -0.057). Estudio 5: el objetivo de este estudio fue conocer si la velocidad de la marcha y la fuerza de prensión manual se asociaban con el deterioro cognitivo. Además, se examinó el posible rol mediador de la velocidad de la marcha y la fuerza de prensión manual sobre el deterioro cognitivo asociado al envejecimiento.Participaron 4416 colombianos con una edad igual o mayor a 60 años. Los resultados destacaron la estrecha relación entre la velocidad de la marcha y fuerza muscular sobre la cognición. También, los análisis de mediación arrojaron que estos dos componentes de la condición física mediaban el deterioro cognitivo asociado al envejecimiento.Introduction: During aging, a series of biochemical and physical changes occur, affecting the main functions of the human body. There is sufficient scientific evidence that physical inactivity aggravates weight gain, fat tissue, and muscle mass loss. So, physical inactivity worsens older adults' health and, therefore, the functions in daily life. However, the role that physical fitness plays among common comorbidities in older adults is unknown. The papers presented in this Doctoral Thesis are based on results obtained from the analysis of the database of the National Study of Health, Well-being and Aging, SABE Colombia 2015 Study 1: The aim was to know the prevalence of probable sarcopenia according to the European Working Group's updates on Sarcopenia in Older People 2 and explore the associated factors. The analysis included 5237 Colombian men and women aged 60 years or older. The prevalence of probable sarcopenia was 46.5% (95% CI: 45.1 ─ 47.8). Physical inactivity (OR = 1.35, 95% CI = 1.14 ─ 1.59), diabetes (OR = 1.32, 95% CI = 1.11 ─ 1.56) and arthritis (OR = 1, 44, 95% CI = 1.25 ─ 1.67), were closely related to probable sarcopenia. Study 2: This study aimed to determine if the speed of the gait moderated the association between obesity and functional dependence. Also, the thresholds for moderation were examined according to the Johnson-Neyman statistical technique. A total of 20,507 Colombian older adults participated. The results indicated that gait speed moderated (β = 0.081; 95% CI: 0.045 ─ 0.117) the association between obesity and functional dependence. The thresholds below which the gait speed negatively moderated the association were 1. 06 m / s.Study 3: The aim was to determine whether excess central adiposity is related to functional dependence and whether this association was moderated by handgrip strength. Four thousand one hundred sixty-nine individuals older than 59 years participated in this study. The results highlighted the mediating role of manual grip strength on the inverse relationship between excess adiposity and functional dependence. The thresholds obtained by the Johnson-Neyman technique were 0.35 kg / kg2 and 0.62 kg / kg2. Doctorado en Ciencias de la Salud Autor: Miguel Ángel Pérez Sousa 13 Study 4: The study aimed to know if the loss of muscle strength associated with excess central adiposity could be mediated by glucose level in the blood. A total of 1571 Colombian older adults participated in the study. The results indicated that blood glucose mediated the detrimental effect of excess central adiposity on muscle strength (β = -0.069, 95% CI = -0.082 - -0.057). Study 5: This study's objective was to find out if gait speed and handgrip strength were associated with cognitive impairment. Besides, the possible mediating role of gait speed and handgrip strength on cognitive impairment associated with aging was examined. 4416 Colombians with age equal to or greater than 60 years participated. The results highlighted the close relationship between gait speed and muscle strength on cognition. Also, the mediation analyzes showed that these two components of physical condition mediated the cognitive deterioration associated with aging

Body composition, lung function, blood pressure, and muscular strength: a comparative study

Background: The loss of balance between components of body composition is significantly linked to a wide range of adverse clinical outcomes. Whilst the sharp rise in the rate of adiposity-based chronic diseases has caused substantial health concerns across the globe, sarcopenia has emerged as an important risk factor for increased morbidity and mortality among the aging population. Therefore, assessment of body composition phenotypes using the conceptual model of metabolic capacity and metabolic load enables an insightful evaluation of metabolic homeostasis association with health outcomes. Nevertheless, the evidence on such associations in the adult population is still lacking. Objectives: To examine the relationship of anthropometric measures with total and segmental adiposity and muscularity; to investigate variations of blood pressure across body composition phenotypes; to explore the interaction effect of fatness and leanness on lung function, and to evaluate bidirectional association of lung function and blood pressure. Study design and subjects: This project was a cross-sectional study of fifty healthy adults (22 men, 28 women) aged 19-65 years old. Anthropometric, body composition (Tanita MC980 and InBody 720 segmental multifrequency bioelectric impedance analysers, and the BODPOD air displacement plethysmography system), blood pressure (OMRON M7 automated oscillometric monitor), grip strength (Takei 5001 analogue dynamometer) and spirometric (COSMED Quark PFT) measurements were carried out in Nutrition Physiology Laboratory at London Metropolitan University from 2016 to 2018. Statistical analysis: Moderation analyses of the associations between body composition, blood pressure and lung function were conducted by the PROCESS modelling tool for SPSS. Results: None of the anthropometric measures were exclusively related to muscle mass. Neck circumference (NC) and upper arm circumference (AC) were the strongest and a body shape index (ABSI) was the only negative predictor of total and segmental muscularity in the entire population. Also, waist to height ratio (WHtR), waist circumference (WC), waist to hip ratio (WHR) and body mass index (BMI) were all strong correlates of total, truncal, visceral and upper arm fatness. None of the anthropometric measurements showed moderate or strong correlations with lower limb fatness. Fat mass (FM) to fat-free mass (FFM) ratio was only significantly associated with diastolic pressure (DBP) (ꞵ=17.6, p<0.001) whereas truncal FM (TFM) to appendicular skeletal muscle mass (ASM) ratio was associated significantly with systolic pressure (SBP) (ꞵ=15.94, p<0.01), DBP (ꞵ=27.47, p<0.001) and pulse pressure (ꞵ=-11.38, p<0.01). Stature-normalised truncal and appendicular adiposity (TFMI, AFMI) impaired lung function (FEV1, FVC and FEF25-75%) respectively at high levels of truncal and appendicular muscularity (TSMI, ASMI). The negative impact of whole-body (high FM/FFM) and segmental (high TFM/ASM) metabolic overload on expiratory flow rate (FEV1) was respectively conditioned on low DBP and high SBP (ꞵ=- .104, p<0.01, ꞵ=-.163; p<0.001). Negative effect of increased FM/FFM and TFM/ASM on FEV1 and FVC was also operable at high levels of grip strength. There was a bidirectional association between lung function and systemic blood pressure. SBP and DBP were independently and negatively associated with FEV1 (ꞵ=-.011 and -.019; p<0.001) and FVC (ꞵ=-.011 and -.022; p<0.001). FEV1 and FVC demonstrated inverse associations with SBP (standardised ꞵ=-.38 and -.30; p<0.001) and DBP (standardised ꞵ=-.35 and -.40; p<0.001). Notably, the effect of FEV1 and FVC on SBP was operated at higher levels of visceral adiposity whilst their influence on DBP was conditioned on higher levels of FFMI. Conclusion: Whole-body and segmental metabolic homeostasis, pulmonary function and systemic blood pressure are complexly cross-linked. Therefore, phenotyping the individuals with or at risk of respiratory diseases and/or cardiometabolic disorders by their total and regional body composition, spirometric, and haemodynamic characteristics may result in more accurate risk stratification, personalised care and effective management strategies, leading to improved clinical outcomes, survival and quality of life

Aptidão física, biomarcadores inflamatórios e metabólicos em adolescentes

A presente tese tem dois objetivos principais; 1) verificar as associações entre vários biomarcadores inflamatórios e metabólicos com o risco cardiometabólico, em adolescentes e 2) verificar as associações entre a aptidão cardiorrespiratória e aptidão muscular e biomarcadores inflamatórios e metabólicos, no risco cardiometabólico, em adolescentes. Para esse efeito, esta tese que faz uso do modelo Escandinavo de tese e apresenta 7 artigos originais, sendo os dois primeiros para responder ao primeiro objetivo e outros 5 artigos para ao segundo objetivo. Este estudo transversal contou com uma amostra de 529 adolescentes entre 12 e 18 anos da região Norte de Portugal que participaram do LabMed Physical Activity Study, em 2011. Procedimentos estandardizados foram utilizados para medir e estimar indicadores da aptidão cardiorrespiratória (teste de vai e vem), aptidão muscular (prensa manual e salto de impulsão horizontal), adiposidade, estagio maturacional, estatuto socioeconómico e adesão à dieta Mediterrânea. Foram avaliados também vários biomarcadores inflamatórios e metabólicos. Os resultados principais deste estudo indicam: i) o potencial de vários fatores de risco não tradicionais (proteína C reativa, C3, C4, leptina, fibrinogénio e a razão adiponectina/leptina) em identificar um risco cardiometabólico mais elevado, bem como a potencial habilidade discriminatória da utilização de um clustered score de biomarcadores inflamatórios (InflaScore); ii) a adiponectina associa-se de forma inversa com a aptidão cardiorrespiratória e a aptidão muscular; iii) os níveis de aptidão muscular e de aptidão cardiorrespiratória estão inversamente associados com o InflaScore; a combinação de um alto perfil inflamatório e baixa aptidão muscular ou cardiorrespiratória aparentam potencializar os efeitos deletérios da saúde metabólica. Os estudos apresentados nessa tese reforçam e sublinham a importância da prevenção e monitorização precoce dos fatores de risco cardiometabólicos. Continuam a ser necessários esforços futuros para identificar características clínicas em crianças e adolescentes que poderiam ser utilizadas em triagem para prevenção de risco de DCV na idade adulta. No entanto, do ponto de vista da saúde pública, a promoção de um estilo de vida saudável continua a ser o foco prioritário. Apesar das limitações impostas pelo desenho transversal deste estudo, as consequências deletérias atribuídas ao processo de inflamação de baixo grau parecem poder ser contrariadas, até certo ponto, pela manutenção dos níveis adequados da aptidão cardiorrespiratória e aptidão muscular. Além disso, a aptidão muscular parece associar-se ao perfil inflamatório e cardiometabólico, independentemente da aptidão cardiorrespiratória e de outros confundidoresThis thesis has two main aims: 1) to verify the associations between several inflammatory and metabolic biomarkers with cardiometabolic risk, in adolescents and 2) to investigate the associations between cardiorespiratory fitness and muscular fitness and inflammatory and metabolic biomarkers on cardiometabolic risk, in adolescents. For this purpose, this thesis makes use of the Scandinavian thesis model and presents 7 original articles, being the first two to respond to the first aim and another 5 articles for the second aim. This cross-sectional study included a sample of 529 adolescents aged between 12 and 18 years, from the Northern region of Portugal, who participated in the LabMed Physical activity study in 2011. Standardized procedures were used to measure and estimate indicators of cardiorespiratory fitness (shuttle-run-test) muscular fitness (handgrip and standing long jump), adiposity, pubertal stage, socioeconomic status, and adherence to the Mediterranean diet. Several inflammatory and metabolic biomarkers were also assessed. In this study, 3 mains results were verified; i) the potential of several nontraditional risk factors (C-reactive protein, C3, C4, leptin, fibrinogen and the adiponectin/leptin ratio) to identify a higher cardiometabolic risk, as well as the potential discriminatory ability of using a clustered score of biomarkers inflammatory (InflaScore); ii) adiponectin is inversely associated with cardiorespiratory fitness and muscular fitness; iii) higher levels of muscular fitness and cardiorespiratory fitness are inversely associated with InflaScore; the combination of a high inflammatory profile and low muscular or cardiorespiratory fitness seems to potentiate the deleterious effects of metabolic health. The results presented in this thesis reinforce and underline the importance of early prevention and cardiometabolic risk factors monitoring. Further efforts are needed to identify clinical features in children and adolescents that could be used in screening to prevent CVD risk in adulthood. However, from the point of view of public health, the promotion of healthy lifestyles should remain the priority focus. Despite the limitations imposed by the cross-sectional design of this study, the deleterious consequences attributed to the process of low-grade inflammation seem to be counteracted to some extent by maintaining adequate levels of cardiorespiratory fitness and muscular fitness. In addition, muscular fitness seems to influence the inflammatory profile and cardiometabolic health, independently of cardiorespiratory fitness and other confounder

Investigating the Relationship between Markers of Ageing and Cardiometabolic Disease

Human ageing is accompanied by characteristic metabolic and endocrine changes, including altered hormone profiles, insulin resistance and deterioration of skeletal muscle. Obesity and diabetes may themselves drive an accelerated ageing phenotype. Untangling the causal web between ageing, obesity and diabetes is a priority in order to understand their aetiology and improve prevention and management. The role of biological ageing in determining the risk of obesity and associated conditions has often been examined using mean leukocyte telomere length (LTL), a marker of replicative fatigue and senescence. However, considering phenotypes which represent different domains of biological and functional ageing as exposures for obesity and related traits could allow the elucidation of new understudied phenotypes relevant to cardio-metabolic risk in the wider population. This PhD considers the causal role of (1) hand grip strength (HGS), a marker of overall strength and physical functioning, and (2) resting energy expenditure, an indicator of overall energy metabolism and the major component of daily energy expenditure, in cardio-metabolic risk. I also characterise a new and readily-quantifiable marker of age-related genomic instability, mosaic loss of the Y chromosome (mLOY). Observational evidence implicates each of these phenotypes in cardio-metabolic conditions and intermediate phenotypes. However, it is not possible to infer causality from these observational associations due to confounding and reverse-causality. Mendelian randomisation offers a solution to these limitations and can allow the causal nature of these relationships to be investigated. Using population-based data including UK Biobank, this thesis presents the first large-scale genetic discovery effort for each trait and provides new biological insight into their shared and separate aetiology. I used identified variants to investigate the bidirectional causal associations of each trait with cardio-metabolic outcomes, intermediate phenotypes and other related traits such as frailty and mortality. In total I identified 16 loci for hand grip strength, 19 for mLOY, and one signal for REE. I have shown that HGS is likely to be causally linked to fracture risk, and I have identified the important shared genetic architecture between mLOY, glycaemic traits and cancer. I have also demonstrated that at least one known genetic variant contributing to obesity risk acts partially via reduced REE. Overall the findings of my PhD contribute to our wider understanding of the aetiological role of ageing processes in metabolic dysfunction, and have implications for both basic science and translational applications.This doctoral thesis was supported by a UK Medical Research Council (MRC) PhD Studentship to D Wright, under a Doctoral Training Partnership (DTP) Award to the MRC Epidemiology Unit

Physical Activity, Wellness and Health: Challenges, Benefits and Strategies

Regular physical activity (PA) is both a preventive measure and a cure for non-communicable diseases. Moreover, PA improves mental health, quality of life, and well-being. Conversely, physical inactivity and sedentary lifestyles have negative impacts on individuals, families, and society, as evidenced in particular by the spread of the obesity epidemic. PA has proven to be a low-cost alternative for the treatment and prevention of disease. Therefore, interventions to prevent avoidable diseases by increasing the proportion of physically active people are fundamental. The Special Issue “Physical Activity, Wellness and Health: Challenges, Benefits and Strategies” was collected research articles on anthropometric determinants of health and performance, PA and healthy habits, exercise and diet, exercise and body composition, interventions to promote PA for people of all ages, strategies for the implementation of an active life, and the beneficial effects of exercise on metabolic syndrome. A total of 20 articles were published, falling mainly into the following three areas: anthropometry, health, and sport; health benefits of exercise; population studies and strategies for an active life. All of the studies support strategies to promote PA and reduce sedentary behavior among adolescents, adults and the elderly. There is no doubt that regular exercise is beneficial to health, but the general population should be encouraged to engage in more of it

Effects of exercise training on adolescent cardiometabolic health and performance

The studies described in this thesis were undertaken to examine the effect of physical fitness, adiposity and acute bouts of ecologically valid exercise on risk factors for cardiometabolic diseases in adolescents. Specifically, the relationship between physical fitness (measured as performance on the multi-stage fitness test (MSFT), the blood lactate response to submaximal exercise and V̇ O2 peak) and adiposity with traditional (insulin sensitivity and blood pressure) and novel (pro- and anti-inflammatory cytokine concentration) risk factors for cardiometabolic diseases during adolescence was examined. In addition, a series of studies was undertaken to examine the inflammatory, glycaemic and insulinaemic responses to acute bouts of games-based activity (60 min of basketball) and high intensity intermittent exercise in adolescents. The effect of differing exercise durations (30 vs. 60 min) on the glycaemic and insulinaemic responses to intermittent activity was also examined (Chapter VI). Finally, the effect of continuous training versus remaining inactive on performance on physical capacity tests, V̇ O2 peak, adiposity and risk factors for cardiometabolic diseases was examined in adolescents across a 2-year follow-up. Throughout the present thesis a comprehensive panel of inflammatory cytokines (including IL1β, IL-6, IL-10, TNF-α) and C-reactive protein was measured alongside blood glucose and plasma insulin concentration. For the epidemiological studies presented in Chapters Ⅳ and ⅤII the inflammatory cytokines measured were an indication of low-grade chronic inflammation in the adolescents, whilst the blood glucose and plasma insulin concentrations were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). In contrast, in Chapters V and Ⅵ, the measurement of pro-inflammatory (IL-1β, TNF-α and CRP) and antiinflammatory (IL-6 and IL-10) cytokines, blood glucose and plasma insulin concentrations were used to examine the inflammatory, glycaemic and insulinaemic responses to acute bouts of games-based and high intensity intermittent activity. The first experimental study (Chapter Ⅳ) examined the effect of performance on the MSFT, V̇ O2 peak and adiposity on risk factors for cardiometabolic diseases in adolescents. Following ethical approval, 121 adolescents (10 - 12 years) were recruited from local secondary schools and sports clubs. Risk factors for cardiometabolic disease (inflammatory cytokines, blood glucose and plasma insulin concentrations) were determined from a fasted capillary blood sample. Participants were separated into quartiles based upon distance run during the MSFT, the blood lactate response to submaximal exercise, V̇ O2 peak, and sum of four skinfolds. Data were analysed using two-way between-subjects ANCOVA and multiple linear regression. Participants with the lowest performance on the MSFT had higher blood concentrations of IL6 (3.25 ± 0.25 pg.mL-1 ) and IL-1β (4.78 ± 0.54 pg.mL-1) and lower concentrations of IL-10 (1.80 ± 0.27 pg.mL-1) when compared with all other quartiles (all p 0.05). Adiposity was the only predictor of plasma insulin concentration (β = 0.515; p < 0.001) and blood pressure (diastolic β = 0.259; p = 0.042; mean arterial pressure β = 0.322; p = 0.011). In conclusion, performance on the MSFT, but not V̇ O2 peak, was associated with a favourable inflammatory profile in adolescents; whilst adiposity was adversely associated plasma insulin, diastolic and mean arterial blood pressure. These findings demonstrate that enhanced performance on the MSFT and maintenance of a healthy body composition attenuate the presence of risk factors for cardiometabolic diseases in adolescents. The second experimental chapter (Ⅴ) aimed to investigate the inflammatory, glycaemic and insulinaemic responses to an acute bout of ecologically valid games-based activity in adolescents. Thirty-nine school children aged 11 - 13 years were recruited to the present study and completed exercise (E) and rested (R) trial in a counterbalanced, randomised crossover design. Following a standardised breakfast, participants completed 1 h games‐based activity (basketball). Capillary blood samples were taken at baseline, immediately and 1 h post‐exercise and 30, 60 and 120 min following a standardised lunch. A final fasted capillary blood sample was taken the next morning. Data were analysed using repeated measures ANOVA. IL‐6 concentration was higher on day one of the exercise trial (E 3.4 ± 0.4: R 2.7 ± 0.4 pg.mL−1; p = 0.006), as was the anti‐inflammatory IL‐6: TNF‐α ratio (E 5.53 ± 0.93: R 3.75 ± 0.45; p = 0.027). Anti‐inflammatory cytokine IL‐10 increased on day two of the exercise trial (E 2.11 ± 0.23: R 1.66 ± 0.16 pg.mL−1; p = 0.032). Insulin sensitivity was also enhanced on the exercise trial with a reduction in postprandial plasma insulin iAUC (E 2310 ± 834: R 3122 ± 1443 mU.L −1 x120 min; p < 0.001). Such findings suggest that games‐based activity is an ecologically valid mode of exercise to elicit beneficial effects on risk factors for cardiometabolic diseases in adolescents. The third experimental chapter (Ⅵ) examined the effects of differing durations (30 min vs. 60 min) of high intensity intermittent activity on postprandial glycaemic and insulinaemic responses in adolescents. Thirty-one participants (13.6 ± 0.49 years) were recruited and completed a 30 min exercise trial, 60 min exercise trial and rested control trial in a randomised, counter-balanced order. The Loughborough Intermittent Shuttle Test was the chosen mode of high intensity intermittent exercise. Capillary blood samples were taken at baseline, immediately and 1 h post‐exercise and 30, 60 and 120 min following a standardised lunch. On day two of the study following the consumption of a standardised breakfast further blood samples were taken at 30 min, 60 min and 120 min to observe the postprandial glycaemic and insulinaemic responses. Data were analysed using a three-way repeated measures ANOVA (trial*time*sex). The pattern of change in blood glucose concentration differed across trials (p = 0.001) as postprandial blood glucose concentration was lower 1 h post-exercise during the 30 min (3.8 ± 0.6 mmol.L -1; p = 0.022) and 60 min trials (3.8 ± 0.6 mmol.L -1; p = 0.017) compared to the rested control trial (4.2 ± 0.9 mmol.L -1 ). Furthermore, postprandial plasma insulin concentration was lower 1 h following the standardised lunch during the 60 min LIST trial when compared with the rested control trial (60 min LIST: 199.1 ± 125.9 pmol.L -1: rested trial 259.4 ± 193.7 pmol.L -1; p = 0.015). There was no difference in blood glucose concentration, plasma insulin concentration and HOMA-IR across trials on day two of the study. The present study suggests that 60 min high intensity intermittent running is an ecologically valid mode of exercise that enhances the regulation of blood glucose and insulin sensitivity in adolescents. Furthermore, a shorter bout of high intensity intermittent exercise (30 min) was also as effective in improving the regulation of blood glucose concentration as 60 min of exercise in adolescents. Such findings support the government physical activity guidelines that suggest young people should participate in 60 min of moderate-to-vigorous physical activity per day. The final experimental study (Chapter Ⅶ) longitudinally examined (during a 2-year followup) the effect of continued training in comparison to remaining recreationally active during childhood and adolescence on traditional and novel risk factors for cardiometabolic diseases and performance on physical capacity tests. In addition, change in performance and V̇ O2 peak and change in risk factors for cardiometabolic diseases were examined to identify whether a relationship existed between training and adolescent health during puberty. From the original cross-sectional sample, 61 adolescents (12 – 14 years) agreed to complete the study. In conjunction with the methods employed in Chapter Ⅳ, low-grade chronic inflammation, blood glucose and plasma insulin concentrations were determined from a fasted capillary blood sample. Participants completed a MSFT and a V̇ O2 peak test, whilst body composition was assessed as the sum of four skinfolds and waist circumference. Data were analysed via a mixed methods ANOVA (training group*time*sex). Overall, the trained group had lower concentrations of pro-inflammatory cytokines IL-6 (trained 3.52 ± 1.54 pg.mL-1: untrained 4.49 ± 1.81 pg.mL-1 ; p = 0.005) and IL-1β (trained 3.52 ± 2.11 pg.mL-1: untrained 5.46 ± 3.95 pg.mL1; p = 0.007) than the untrained group, yet had higher concentrations of anti-inflammatory cytokine IL-10 (trained 3.31 ± 2.81 pg.mL-1: untrained 2.37 ± 1.36 pg.mL-1; p = 0.008). Overall, the trained group had a lower HOMA-IR than the untrained group (trained 1.4 ± 1.6: untrained 2.7 ± 3.5; p = 0.019). Finally, change in distance run on the MSFT was inversely associated with change in plasma insulin concentration (r (46) = -0.28; p = 0.062) and change in blood lactate concentration during submaximal exercise was negatively correlated with change in HOMA-IR (r (21) = -0.42; p = 0.055); whereas, V̇ O2 peak was not related to any of the risk factors for cardiometabolic diseases. The findings of the present study suggest that continued training from childhood into adolescence improves cardiometabolic health, as evidenced by a favourable inflammatory profile and enhanced insulin sensitivity. Furthermore, as the change in performance on distance run on the MSFT and the blood lactate response to submaximal exercise (which are both indicators of training status) was inversely associated with change in risk factors for metabolic health there is further support of a causal relationship between physical fitness and cardiometabolic health in adolescents. Overall, the findings from the present thesis suggest that regular participation in exercise (of sufficient intensity to enhance performance on the MSFT or to reduce the blood lactate response to submaximal exercise) reduces the presence of both traditional and novel risk factors for cardiometabolic diseases in healthy, normal weight adolescents. Furthermore, intermittent activity (performed as games-based activity and high intensity intermittent running) is an ecologically valid mode of exercise that stimulated an inflammatory, glycaemic and insulinaemic response in adolescents that elicited protective effects for cardiometabolic health, including an anti-inflammatory cascade and enhanced insulin sensitivity. If repeated regularly such exercise has the potential to reduce cardiometabolic risk factors in young people, thus preventing the early development of chronic diseases such as cardiovascular disease and type 2 diabetes. Taken together, the findings of this thesis have important practical implications, emphasising that regular exercise optimises cardiometabolic health during adolescence, which should be considered by Government health policy makers when developing recommendations for lifelong health. In particular, the findings of this thesis suggest that adolescents should participate in intermittent activity on a daily basis, to enhance their cardiometabolic health

Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obesity-induced CKD. Methods: Groups of male C57Bl/6J mice (n = 99 in total) were fed a low (10% lard) or high (45% lard) fat diet for a maximum of 52 weeks. Mice were sacrificed after 24, 40 and 52 weeks. Whole blood samples, kidneys and adipose tissues were collected. The development of adipose and renal tissue inflammation was assessed on gene expression and protein level. Adipocytokine levels were measured in plasma samples. Results: A distinct inflammatory phenotype was observed in the adipose tissue of HFD mice prior to renal inflammation, which was associated with an early systemic elevation of TNF-α, leptin and SAA (1A-C). With aging, sclerotic lesions appeared in the kidney, the extent of which was severely aggravated by HFD feeding. Lesions exhibited typical amyloid characteristics (2A) and pathological severity positively correlated with bodyweight (2B). Interestingly, more SAA protein was detected in lesions of HFD mice. Conclusion: Our data suggest a causal link between obesity induced chronic inflammation and AA amyloidosis in C57Bl/6J mice. Though future studies are necessary to prove this causal link and to determine its relevance for the human situation, obesity may hence be considered a risk factor for the development and progression of renal AA amyloidosis in the course of CKD. (Figure Presented)

A Systematic Review and Meta-Analysis of the Incidence of Injury in Professional Female Soccer

The epidemiology of injury in male professional football is well documented and has been used as a basis to monitor injury trends and implement injury prevention strategies. There are no systematic reviews that have investigated injury incidence in women’s professional football. Therefore, the extent of injury burden in women’s professional football remains unknown. PURPOSE: The primary aim of this study was to calculate an overall incidence rate of injury in senior female professional soccer. The secondary aims were to provide an incidence rate for training and match play. METHODS: PubMed, Discover, EBSCO, Embase and ScienceDirect electronic databases were searched from inception to September 2018. Two reviewers independently assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement using a 22-item STROBE checklist. Seven prospective studies (n=1137 professional players) were combined in a pooled analysis of injury incidence using a mixed effects model. Heterogeneity was evaluated using the Cochrane Q statistic and I2. RESULTS: The epidemiological incidence proportion over one season was 0.62 (95% CI 0.59 - 0.64). Mean total incidence of injury was 3.15 (95% CI 1.54 - 4.75) injuries per 1000 hours. The mean incidence of injury during match play was 10.72 (95% CI 9.11 - 12.33) and during training was 2.21 (95% CI 0.96 - 3.45). Data analysis found a significant level of heterogeneity (total Incidence, X2 = 16.57 P < 0.05; I2 = 63.8%) and during subsequent sub group analyses in those studies reviewed (match incidence, X2 = 76.4 (d.f. = 7), P <0.05; I2 = 90.8%, training incidence, X2 = 16.97 (d.f. = 7), P < 0.05; I2 = 58.8%). Appraisal of the study methodologies revealed inconsistency in the use of injury terminology, data collection procedures and calculation of exposure by researchers. Such inconsistencies likely contribute to the large variance in the incidence and prevalence of injury reported. CONCLUSIONS: The estimated risk of sustaining at least one injury over one football season is 62%. Continued reporting of heterogeneous results in population samples limits meaningful comparison of studies. Standardising the criteria used to attribute injury and activity coupled with more accurate methods of calculating exposure will overcome such limitations

Nutrition in Chronic Conditions

The effects of nutrition on chronic conditions, such as diabetes, cardiovascular disease, dementia and stroke, continue to generate interest among researchers. This is based on the fact that diet is a modifiable risk factor for these diseases, which manifest either as single entities or in co-morbid states in individuals and populations around the world. In particular, the prevalence of diabetes and cardiovascular disease is on the increase, especially in developed countries, but also in developing economies, partly due to lifestyle changes, including diet. For example, ischaemic heart disease is the leading cause of death globally. When combined with stroke, they accounted for 15 million deaths in 2015 and are the world’s greatest killers (WHO, 2017). Furthermore, WHO (2016) reported that there were an estimated 422 million adults living with diabetes in 2014. This is significantly higher than the 108 million in 1980, representing a rise in worldwide diabetes prevalence from 4.7% in 1980 to 8.5% in 2014 among the adult population. These chronic conditions and their associated complications have significant implications for morbidity and mortality, not to mention huge costs to the health services around the world. The composition of the diet, the proportion and types of macronutrients and micronutrients present in the diet are major contributors to these diseases. In addition, the beneficial effects of nutritional interventions have been well documented although differences remain among researchers with respect to their overall impact. The evaluation of the role of nutrition in chronic conditions draws on its effect on body weight and body composition, glycaemic and insulin excursions and vascular remodelling. The effect of the diet in modulating gut microbiota dysbiosis is also an evolving area of research. Therefore, this Special Issue Book on “Nutrition and Chronic Conditions” is aimed at examining the effect of nutrition in the development, care and management of chronic conditions