There is considerable evidence to show that obesity is associated with the development of heart failure independent of traditional risk factors. However, clarity is required on the process involved in the transition from obesity-associated left ventricular hypertrophy (LVH) to LV dysfunction. In the present thesis I evaluated the extent to which central obesity explains variations in LV diastolic function at a community level independent of LV mass (LVM), LV remodelling or haemodynamic factors; whether obesity-related increases in LVM exceeding that predicted by workload (inappropriate LVM [LVMinappr] or alternative haemodynamic factors explains variations in LV ejection fraction (EF) at a community level; whether regression of LVMinappr is more closely associated with improvements in EF than LVM or LVM index (LVMI); and whether obesity-associated insulin resistance may explain decreases in LV diastolic function and variations in LVMinappr. Data were obtained in either 626 or 478 participants whom were representative of a randomly selected community sample and in 168 mild to moderate hypertensives treated for 4 months. In 626 randomly selected participants over 16 years of age from a community sample with a high prevalence of excess adiposity (~24% overweight and ~43% obese) after adjustments for a number of confounders including age, sex, pulse rate, conventional diastolic (or systolic) blood pressure (BP), antihypertensive treatment, LVMI and the presence of diabetes mellitus or an HbA1c>6.1%; waist circumference (p=0.0012) was independently and inversely associated with a reduced early-ro-late transmitral velocity (E/A), with similar findings noted for e’/a’ in a subset of 212 participants with tissue Doppler measurements. Waist circumference-E/A relationships persisted even after adjustments for other adiposity indices including body mass index (BMI) (p<0.05-0.005). No independent relationships between adiposity indices and E/e’ were noted (n=212). In contrast to the effects on diastolic function, waist circumference was not correlated with EF (p=0.83). The independent relationship between waist circumference and E/A was second only to age and similar to BP in the magnitude of the independent effect on E/A. The inclusion of relative wall thickness rather than LVMI in the regression equation produced similar outcomes. The inclusion of carotid-femoral pulse wave velocity (PWV), or 24-hour BP as confounders, failed to modify the relationship between waist circumference and E/A. Thus, waist circumference is second only to age in the impact of the independent association with E/A in a community sample with a high prevalence of excess adiposity. This effect was not accounted for by left ventricular hypertrophy or remodelling, 24-hour BP or arterial stiffness. In 478 randomly selected participants from a community sample, waist circumference, but not BMI was independently associated with the homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR was inversely correlated with E/A (p<0.0001) and in a multivariate model with adjustments for waist circumference, age, sex, conventional diastolic or systolic BP, diabetes mellitus or an HbA1c>6.1%, regular tobacco use, regular alcohol intake, pulse rate, treatment for hypertension and either LVMI or LV relative wall thickness in the model, the relationship betwreen HOMA-IR and E/A persisted (partial r=-0.13 to 0.14, p<0.005). With further adjustments for either 24-hour systolic or diastolic BP (partial r=-0.11, p<0.05, n=351) or for aortic PWV (partial r=-0.11, p<0.02, n=410), the independent relationship between HOMA-IR and E/A also remained. Therefore, the relationship between indices of an excess adiposity and abnormalities in LV diastolic function may be explained in-part by insulin resistance beyond haemodynamic factors. In 626 randomly selected adult participants from a community sample with a high prevalence of obesity, the strongest independent predictor of LVMinappr was BMI (p<0.0001). With adjustments for LV stress and other confounders there was a strong inverse relationship between LVMinappr and EF (partial r=-0.41, p<0.0001), whilst only modest inverse relations between LVM or LVMI and EF were noted (partial r=-0.07 to -0.09, p<0.05-0.09)(p<0.0001, comparison of partial r values). The independent relationship between LVMinappr and EF persisted with further adjustments for LVM or LVMI (partial r=-0.52, p<0.0001). LVMinappr and LV midwall fractional shortening were similarly inversely related (p<0.0001) and these relations were also stronger than and independent of LVM or LVMI. In conclusion, in a community sample with a high prevalence of obesity, inappropriate LVM is strongly and inversely related to variations in EF independent of and more closely than LVM or LVMI and BMI was the strongest independent determinant of inappropriate LVH. Therefore LVH is a compensatory response to workload, but when exceeding that predicted by workload, as may occur in obesity, is associated with LV systolic chamber decompensation. In 168 mild-to-moderate hypertensives treated for 4 months, although in patients with an LVMI>51g/m2.7 (n=112)(change in LVMI=-13.7±14.0 g/m2.7, p<0.0001), but not in patients with an LVMI≤51g/m2.7(n=56)(change in LVMI=1.3±9.3 g/m2.7) LVMI decreased with treatment; treatment failed to increase EF in either group (1.2±10.8% and 2.7±10.7% respectively). In contrast, in patients with inappropriate LVH (LVMinappr>150%, n=33) LVMinappr decreased (-32±27%, p<0.0001) and EF increased (5.0±10.3%, p<0.0001) after treatment, whilst in patients with a LVMinappr≤150% (n=135), neither LVMinappr (-0.5±23%), nor EF (0.9±10.3%) changed with therapy. With adjustments for circumferential LV wall stress and other confounders, whilst on-treatment decreases in LVM or LVMI were weakly related to an attenuated EF (partial r=0.17, p<0.05), on-treatment decreases in LVMinappr were strongly related to increases in EF even after further adjustments for LVM or LVMI (partial r=-0.63, confidence interval=-0.71 to -0.52, p<0.0001). In conclusion, decreases in LVMinappr are strongly related to on-treatment increases in EF beyond changes in LVM and LVMI. LVH can therefore be viewed as a compensatory change that preserves EF, but when in excess of that predicted by stroke work, as a pathophysiological process accounting for a reduced EF. In 478 participants of a randomly selected community sample with adjustments for waist circumference, age, sex, conventional systolic BP, diabetes mellitus or an HbA1c>6.1%, regular tobacco use, regular alcohol intake, pulse rate, and treatment for hypertension, an independent relationship between HOMA-IR and LVMinappr was noted (partial r=0.14, p<0.002). With further adjustments for either 24-hour systolic BP (partial r=0.11, p<0.05, n=351), aortic PWV (partial r=0.13, p<0.02, n=410), or circumferential LV wall stress (partial r=0.12, p<0.02, n=478) the independent relationship between HOMA-IR and LVMinappr also remained. Thus, the relationship between indices of an excess adiposity and LVM beyond haemodynamic factors may be explained in-part by insulin resistance. In conclusion, the results of the present thesis provide clarity on the process involved in the transition from obesity-associated LVH to LV dysfunction. In the present thesis I demonstrated that an index of central obesity explains a considerable proportion of the variation in LV diastolic function at a community level independent of LVM, LV remodelling and haemodynamic factors; that obesity-related increases in LVM exceeding that predicted by workload (LVMinappr) or alternative haemodynamic factors explains a marked proportion of variations in EF at a community level; that regression of LVMinappr is more closely associated with improvements in EF than LVM or LVM index (LVMI); and that obesity-associated insulin resistance may explain decreases in LV diastolic function and variations in LVMinappr and hence EF. Therefore, studies are warranted to evaluate the impact of interventions that improve insulin sensitivity on obesity-related decreases in LV diastolic function and increases in LVMinappr.

published_or_final_version / Pharmacology and Pharmacy / Master / Master of Philosophy

by Patricia Jane Anderson. / "June 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 300-328). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Obesity is closely related to many medical complications such as type 2 diabetes, hypertension and heart failure. Obesity and other factors, including elevated blood glucose levels, hypertension, and dyslipidemia, constitute a constellation of symptoms known as the metabolic syndrome, which are the risk factors for coronary artery disease. Lipocalin-2 is a pro-inflammatory adipokine causally involved in the development of obesity-associated metabolic and cardiovascular diseases. Recent clinical and experimental evidences demonstrate an association between augmented circulating lipocalin-2 and cardiac dysfunction. However, little is known about the detailed roles of lipocalin-2 in regulating pathophysiological functions of the heart. The present study was designed to compare the heart functions of mice with normal (WT) or deficient lipocalin-2 (Lcn2-KO) expression and to examine the molecular mechanisms underlying lipocalin-2-mediated deteriorated effects in hearts. Echocardiographic analysis revealed that the myocardial contractile function was significantly improved in hearts of Lcn2-KO mice, under both standard chow and high fat diet conditions. The heart function before and after I/R injury (20-min of global ischemia followed by 60-min of reperfusion) was assessed using the Langendorff perfusion system. Compared with WT littermates, hearts from Lcn2-KO mice showed improved functional recovery and reduced infarct size following I/R. These phenomena can be observed in mice under both standard chow and high fat feeding conditions. Under baseline condition, the mitochondrial function of hearts from Lcn2-KO mice was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity, markers of biogenesis and oxidative stress, as well as electron microscopic investigation of the mitochondrial ultrastructure. Acute or chronic administration of lipocalin-2 impaired cardiac functional recovery to I/R and dampened the mitochondrial function in hearts of Lcn2-KO mice. These effects were associated with an extensive modification of the fatty acyl chain compositions of intracellular phospholipids. In particular, lipocalin-2 facilitated the redistribution of linoleic acid (C18:2) among different types of phospholipid, including cardiolipin, which is exclusively located in the mitochondria inner membrane. The direct effects of lipocalin-2 on both H9c2 and NCM cells were also examined. TUNEL assay and flow cytometry analysis demonstrated that lipocalin-2 treatment promoted apoptosis in cardiomyocytes. Lipocalin-2 induced an early phase of phosphatidylserine exposure, followed by Bax-translocation and caspase-3 cleavage. The results collectively suggested that lipocalin-2 initiated the intrinsic mitochondria-mediated apoptotic pathway. In the hearts of Lcn2-KO mice, significantly reduced number of apoptotic cells was observed after I/R injury. In conclusion, lacking of lipocalin-2 improved heart function recovery during I/R injury via mitochondrial function restoration, phospholipids remodeling, and inhibition of cardiomyocytes apoptosis. / published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

Fang Yujing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 148-182). / Abstracts in English and Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview of the study --- p.1 / Chapter 1.2 --- Overview of Hypertension --- p.4 / Chapter 1.3 --- Overview of Obesity-Related Hypertension --- p.9 / Chapter 1.3.1 --- Body fat distribution --- p.11 / Chapter 1.3.2 --- Insulin resistance and Hyperinsulinaemia --- p.12 / Chapter 1.3.3 --- Sympathetic nervous system activity --- p.13 / Chapter 1.3.4 --- Genetics of Obesity --- p.15 / Chapter 1.3.4.1 --- Brown adipose tissue (BAT) --- p.15 / Chapter 1.3.4.2 --- Uncoupling protein --- p.16 / Chapter 1.3.4.3 --- Uncoupling Protein 1 Gene --- p.17 / Chapter 1.3.4.4 --- Association of the UCP1 Polymorphism and Weight Gain in Obesity --- p.18 / Chapter 1.4 --- Overview of Genetics of Hypertension --- p.19 / Chapter 1.4.1 --- The Renin-Angiotensin System --- p.19 / Chapter 1.4.1.1 --- Functions of Renin-Angiotensin System --- p.20 / Chapter 1.4.1.2 --- The Renin-Angiotensin System and Hypertension --- p.21 / Chapter 1.4.2 --- Renin --- p.22 / Chapter 1.4.3 --- Angiotensinogen --- p.25 / Chapter 1.4.4 --- Angiotensin-Converting Enzyme (ACE) --- p.29 / Chapter 1.4.4.1 --- Angiotensin-Converting Enzyme Gene --- p.29 / Chapter 1.4.4.2 --- Association of the ACE I/D Polymorphism with Hypertension --- p.30 / Chapter 1.4.4.3 --- Association of the ACE I/D Polymorphism with Other disease --- p.32 / Chapter 1.4.5 --- The Angiotensin II Receptor --- p.35 / Chapter 1.4.5.1 --- Type 1 Angiotensin II Receptor --- p.35 / Chapter 1.4.5.2 --- The Type 1 Angiotensin Receptor Gene --- p.36 / Chapter 1.4.6 --- Dopamine --- p.39 / Chapter 1.4.6.1 --- Dopamine Receptors --- p.42 / Chapter 1.4.6.2 --- The Dopamine D2 Receptor Gene --- p.45 / Chapter 2 --- Aims --- p.47 / Chapter 3 --- Materials and methodology --- p.48 / Chapter 3.1 --- Patient recruitment protocol --- p.48 / Chapter 3.2 --- Subjects --- p.49 / Chapter 3.2.1 --- Classification of Hypertension --- p.50 / Chapter 3.2.2 --- Definition of Dyslipidaemia --- p.51 / Chapter 3.2.3 --- Classification of Diabetes Mellitus --- p.52 / Chapter 3.2.4 --- Definition of Obesity --- p.53 / Chapter 3.2.5 --- Exclusion Criteria --- p.54 / Chapter 3.3 --- Routine Assessment --- p.54 / Chapter 3.3.1 --- Blood Pressure --- p.54 / Chapter 3.3.2 --- Measurements of obesity --- p.55 / Chapter 3.3.2.1 --- Body mass index --- p.55 / Chapter 3.3.2.2 --- Waist to hip ratio --- p.55 / Chapter 3.3.2.3 --- Skin-Fold Thickness --- p.55 / Chapter 3.3.2.4 --- Skinfold Percentage Fat --- p.56 / Chapter 3.3.3 --- Biochemical measurements --- p.56 / Chapter 3.3.3.1 --- Assays measuring biochemical factors from plasma --- p.57 / Chapter 3.3.3.1.1 --- Plasma electrolytes --- p.57 / Chapter 3.3.3.1.2 --- Plasma urate --- p.57 / Chapter 3.3.3.1.3 --- Plasma creatinine --- p.57 / Chapter 3.3.3.1.4 --- Fasting plasma glucose --- p.57 / Chapter 3.3.3.1.5 --- Fasting plasma cholesterol --- p.57 / Chapter 3.3.3.1.6 --- Fasting plasma triglyceride --- p.58 / Chapter 3.3.3.2 --- Assays measuring biochemical factors from urine --- p.58 / Chapter 3.3.3.2.1 --- Urinary electrolytes --- p.58 / Chapter 3.3.3.2.2 --- Urinary creatinine --- p.58 / Chapter 3.3.3.2.3 --- Urinary albumin concentration --- p.58 / Chapter 3.4 --- Extraction of DNA from blood specimen --- p.59 / Chapter 3.5 --- Polymerase Chain Amplification protocols --- p.60 / Chapter 3.5.1 --- Uncoupling protein 1 gene polymorphism --- p.60 / Chapter 3.5.2 --- Angiotensin-Converting Enzyme insertion-deletion polymorphism --- p.62 / Chapter 3.5.3 --- Angiotensin type 1 receptor gene A1166C polymorphism --- p.64 / Chapter 3.5.4 --- Dopamine D2 receptor TaqI polymorphism --- p.66 / Chapter 3.5.5 --- Dopamine D2 receptor TaqI polymorphism --- p.66 / Chapter 3.6 --- Statistical analysis --- p.68 / Chapter 3.6.1 --- Paired sample T test --- p.68 / Chapter 3.6.2 --- Conditional Logistic Regression --- p.68 / Chapter 3.6.3 --- Linkage analysis --- p.69 / Chapter 3.6.3.1 --- Allelic frequency and genotypic distribution --- p.69 / Chapter 3.6.3.2 --- Hardy- Weinberg equilibrium --- p.69 / Chapter 3.6.3.3 --- Parametric analysis --- p.71 / Chapter 3.6.3.4 --- Nonparametric analysis --- p.71 / Chapter 3.6.3.4.1 --- The affected sib pair (ASP) method --- p.74 / Chapter 3.6.3.4.2 --- The affected pedigree member (APM) method of linkage analysis --- p.76 / Chapter 3.6.3.4.3 --- Quantitative traits linkage analysis --- p.79 / Chapter 4 --- Results --- p.81 / Chapter 4.1 --- Description of the characteristics of in siblings --- p.81 / Chapter 4.1.1 --- Siblings and sib-pairs --- p.81 / Chapter 4.1.2 --- Demographic characteristics --- p.81 / Chapter 4.1.3 --- Relationship to age and gender --- p.83 / Chapter 4.1.3.1 --- Hypertension versus age and gender --- p.83 / Chapter 4.1.3.2 --- Central obesity versus age and gender --- p.83 / Chapter 4.1.3.3 --- General obesity versus age and gender --- p.84 / Chapter 4.1.3.4 --- Hypertension-central obesity versus age and gender --- p.84 / Chapter 4.1.3.5 --- Hypertension- general obesity versus age and gender --- p.85 / Chapter 4.1.4 --- Relationship to anthropometric indices --- p.85 / Chapter 4.1.4.1 --- Large proportion of obesity --- p.85 / Chapter 4.1.4.2 --- Hypertension versus anthropometric indices --- p.86 / Chapter 4.1.5 --- Relationship to biochemistry indices --- p.87 / Chapter 4.1.5.1 --- Large proportion of dyslipidaemia --- p.87 / Chapter 4.2 --- Association between disease traits and covariates in discordant sib pairs --- p.87 / Chapter 4.2.1 --- Association between blood pressure and covariates in discordant sib-pairs --- p.87 / Chapter 4.2.2 --- Association between general obesity and covariates in discordant sib-pairs --- p.89 / Chapter 4.2.3 --- Association between obesity related hypertension and covariates in combined discordant sib-pairs --- p.91 / Chapter 4.3 --- Description of the analysis of the polymorphisms of 4 genes which might be related to hypertension and obesity --- p.93 / Chapter 4.3.1 --- The uncoupling protein 1 gene --- p.93 / Chapter 4.3.1.1 --- Comparison of A-G polymorphism in terms of hypertension or obesity --- p.94 / Chapter 4.3.1.2 --- Comparison of A-G polymorphism in terms of HT and obesity --- p.97 / Chapter 4.3.1.3 --- Comparison of characteristics among different genotypes --- p.99 / Chapter 4.3.2 --- The angiotensin-converting enzyme gene --- p.99 / Chapter 4.3.2.1 --- Comparison of the ACE I/D polymorphism in terms of HT --- p.100 / Chapter 4.3.2.2 --- Comparison of characteristics among different genotypes --- p.101 / Chapter 4.3.3 --- The angiotensin type 1 receptor gene --- p.104 / Chapter 4.3.3.1 --- Comparison of the A T1R A1166C polymorphism in terms of HT --- p.104 / Chapter 4.3.3.2 --- Comparison of characteristics among different genotypes --- p.105 / Chapter 4.3.4 --- The Dopamine D2 receptor gene --- p.105 / Chapter 4.3.4.1 --- Comparison of the DRD2 gene TaqI polymorphism in terms of HT --- p.106 / Chapter 4.3.4.2 --- Comparison of the DRD2 gene TaqI polymorphism in terms of general obesity or central obesity --- p.108 / Chapter 4.3.4.3 --- Comparison of the DRD2 gene TaqI polymorphism in terms of general obesity/central obesity and HT --- p.110 / Chapter 4.4 --- Sib pair linkage analysis --- p.113 / Chapter 4.4.1 --- Linkage between each gene and hypertension in our data --- p.114 / Chapter 4.4.1.1 --- Genetic linkage of the marker near the UCP1 gene locus to hypertension --- p.114 / Chapter 4.4.1.2 --- Genetic linkage of the angiotens in-converting enzyme gene locus to hypertension --- p.116 / Chapter 4.4.1.3 --- Genetic linkage of the angiotensin type 1 (AT1) receptor gene locus to hypertension --- p.117 / Chapter 4.4.1.4 --- Genetic linkage of the dopamine D2 receptor gene locus to hypertension --- p.118 / Chapter 4.4.2 --- Linkage between each gene locus and obesity in Hong Kong hypertensive Chinese families --- p.120 / Chapter 4.4.2.1 --- Genetic linkage of the uncoupling protein 1 gene locus to obesity with hypertensive family history --- p.120 / Chapter 4.4.2.2 --- Genetic linkage of the angiotens in-converting enzyme gene locus to obesity with hypertensive family history --- p.123 / Chapter 4.4.2.3 --- Genetic linkage of the angiotensin type 1 receptor gene locus to obesity with hypertensive family history --- p.124 / Chapter 4.4.2.4 --- Genetic linkage of the dopamine D2 gene locus to obesity --- p.127 / Chapter 5 --- Discussion --- p.129 / Chapter 5.1 --- Age-related anomalies --- p.129 / Chapter 5.2 --- Gender-related anomalies --- p.129 / Chapter 5.3 --- Obesity- related hypertension --- p.130 / Chapter 5.4 --- Abnormal biochemical parameters in hypertension --- p.131 / Chapter 5.5 --- Genetic parameters involved in the pathogenesis of hypertension and obesity. --- p.132 / Chapter 5.6 --- The uncoupling protein gene --- p.132 / Chapter 5.6.1 --- Higher frequency in central obese males --- p.132 / Chapter 5.6.2 --- Linkage of systolic blood pressure with G allele --- p.134 / Chapter 5.6.3 --- Metabolic link --- p.135 / Chapter 5.7 --- The angiotensin-converting enzyme gene --- p.137 / Chapter 5.7.1 --- The ACE D allele and hypertension in previous studies --- p.137 / Chapter 5.7.2 --- Positive role of the ACE DD genotype found in our data --- p.139 / Chapter 5.8 --- Angiotensin II type 1 receptor gene --- p.141 / Chapter 5.8.1 --- No linkage with HT --- p.141 / Chapter 5.9 --- Dopamine D2 gene --- p.143 / Chapter 5.9.1 --- Dopamine and obesity --- p.143 / Chapter 5.9.2 --- Linkage with obese and HT --- p.144 / Chapter 5.10 --- Summary of the study --- p.146 / Chapter 5.11 --- Possible further developments in this study --- p.146 / Chapter 6 --- References --- p.148

[Truncated abstract] Introduction: Childhood obesity is currently a serious worldwide public health issue associated with many medical and psychosocial complications. The increasing disease burden with the potential for the development of medical co-morbidities has implications for future health care provision. This thesis adds to the understanding of the medical complications of overweight and obesity in childhood. Design and Aims: Two different, but related, research studies are reported. The first study is a cross-sectional study, designed to quantify the medical complications of childhood obesity in primary school-aged children in Western Australia. This study aims to identify the medical complications of primary school children with overweight/obesity. The study also aims to compare the medical complications of obesity in a community sample who have never sought treatment with a clinical sample who are actively seeking treatment for overweight/obesity. Finally, this study also aims to examine the relationship between the medical complications of childhood obesity and a continuum of children's Body Mass Index z-scores, including those in the normal range. The second study is an exercise intervention study to investigate the effect of exercise on one specific medical complication of obesity, namely insulin resistance. This study aims to determine if a structured eight-week exercise program significantly changes insulin resistance in obese children, and to determine if this decrease in insulin resistance is associated with changes in body composition and inflammatory markers. ... Conclusion: The prevalence of the medical complications of overweight and obesity in primary school children indicates that all children should have body mass index regularly checked from a young age. Children who are overweight/obese should be screened for the presence of co-morbidities despite a young age. Parents and health professionals needs to be educated that childhood obesity is associated with medical co-morbidities and is not simply a social or cosmetic concern. The continuous nature of the BMI z-score/co-morbidities relationship suggests that public health and health education strategies should include adopting a populationbased approach to weight management. This continuous relationship means that even in the normal BMI spectrum, the risk of developing co-morbidities rises with increasing BMI. Such an approach would encourage maintenance of normal weight for all children, rather than targeting overweight/obese children only. Increased activity and decreased sedentary behaviours should be recommended for all children in line with the population-based public health approach suggested above. However, exercise has a specific role in weight management strategies for overweight/obese children, and in management strategies for adiposityrelated co-morbidities. Significant metabolic benefits of exercise occur in the absence of changes in body shape and weight. After an exercise program, simple blood investigations (such as lipid profiles, fasting insulin and OGTTs) are likely to miss important metabolic improvements and anthropometry (BMI calculation, waist circumference) may be more indicative of potential metabolic improvement and decreased co-morbidity risk.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Orientador: Mario Jose Abdalla Saad / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T14:59:49Z (GMT). No. of bitstreams: 1 Dertkigil_SergioSanJuan_M.pdf: 2116703 bytes, checksum: 70e0c18a251483a0c4be5861dc3adee8 (MD5) Previous issue date: 2006 / Resumo: Introdução A obesidade tem sido considerada uma das mais importantes doenças da atualidade, tanto pela sua crescente prevalência quanto pela sua alta relevância de morbi-mortalidade. A segmentação da gordura em seus diferentes compartimentos vem ganhando importância na tentativa de explicar e influir no prognóstico das alterações metabólicas envolvidas na obesidade. Objetivos Estudar os diferentes tipos de compartimentalização de gordura e correlacionar com suas alterações metabólicas mais freqüentes e relevantes. Material e Métodos Foram avaliados 64 pacientes obesos do ambulatório de obesidade do HC-UNICAMP, através de tomografia computadorizada, para medição das gorduras subcutânea, visceral, infiltração hepática, pancreática e muscular, e correlacionar esses achados da distribuição regional de gordura com os fatores metabólicos clássicos, entre os quais, glicemia de jejum, insulinemia de jejum, HOMA-IR, frações de colesterol, marcadores hepáticos (_GT) e medidas antropométricas. Resultados Foram analisados 64 pacientes, 30 homens e 34 mulheres, que demonstraram diferença estatística entre a área de gordura visceral, densidade hepática e muscular, e apresentaram alta correlação com fatores metabólicos clássicos (HOMA-IR, TG e TG/HDL). A área de gordura subcutânea e a densidade pancreática não apresentaram diferenças estatísticas entre os grupos ou com os fatores metabólicos. Os pacientes com baixa quantidade de gordura visceral e alta quantidade de gordura subcutânea, apresentaram fatores metabólicos de menor risco cardiovascular. Nesses pacientes com padrão subcutâneo a densidade muscular e não gordura visceral ou gordura hepática se correlacionou mais fortemente com esses fatores de risco metabólico. Dos fatores utilizados aquele com melhor correlação com a gordura visceral, gordura hepática e muscular foi o índice TG/HDL. Conclusão A deposição da gordura nos compartimentos visceral e hepático apresentam papel importante na gênese da síndrome metabólica em pacientes obesos viscerais, enquanto em pacientes com deposição subcutânea o depósito muscular apresenta a maior correlação com os fatores metabólicos / Abstract: Introdution During past decades obesity is being considered one of the most important disease, both for raising prevalence and high morbi-mortality. The regional distribution of adiposity into different compartments araises as an important marker for the earlier diagnostic of metabolic syndrome. It is well established a strong association between visceral adiposity and several metabolic abnormalities, including type 2 diabetes mellitus, lipid metabolism impairment, hypertension and impaired inflammatory factors that may contribute to increase the risk of cardiovascular disease. Objective. Study the different types of regional adipose depots and to correlate these depots and the metabolic risk factors. Material e Methods Subjects included sixty four obese volunteers who received medical examination (30 men and 34 women) between 2002 and 2005. Inclusion criteria required the subjects to be nonsmokers, BMI > 30 Kg/m2, age between 18 and 60 years. The subjects were evaluated with computed tomography for measurement of visceral adiposity area, subcutaneous area, hepatic density, pancreatic and muscle density, and correlate them with the metabolic risk factors ( fasting plasma glucose, fasting serum insulin, HOMA-IR, cholesterol fractions, hepatic marker (_GT) and anthropometric measurements. Results Visceral adiposity, hepatic density and muscle density were different in gender and showed high correlation with metabolic factors (HOMA-IR, TG e TG/HDL). Subcutaneous area and pancreatic density did not showed correlation with the metabolic factors. The patients with high subcutaneous depot showed lower metabolic risk factors. In those patients, the muscle depot and not the visceral or liver adiposity had strong correlation with metabolic factors. TG/HDL had the strongest relationship with visceral, liver and muscle depots. Conclusion In obese patients, the regional adiposity, in special visceral and liver depots play important roles in the genesis of metabolic syndrome. In subcutaneous obese patients, the muscle depot has the strongest correlation coefficient with metabolic syndrome / Mestrado / Medicina Experimental / Mestre em Fisiopatologia Médica

Abstract Obesity in School Children from the Point of View of a Nurse Working in a GP's Surgery The thesis focuses on the problems of nursing care of children with overweight and obesity. This issue is very urgent nowadays, not only in the Czech Republic, but it is a global problem. Our country holds one of the leading positions in children obesity. Children suffering from overweight and obesity have not only health problems resulting from obesity complications, but also problems in the field of psyche and social relations, particularly among their peers. This is why the right insight into the issue and finding an acceptable solution for the future is so important. The theoretical part deals with the problems of children obesity, the specifics of nursing care of these children within a surgery of a general paediatrician. It also focuses on the needs of children with normal weight and on the needs of overweight children. Four aims were set within the research. The first aim was to map the situation in obesity among school and pre-school children in Benešov District. The second aim was to map services (possibilities of further assistance, treatment) that parents and practitioners may use in treatment of children with overweight and obesity in Benešov District. The third aim was to compare success rate of obesity treatment in children that have already undergone obesity treatment under specialist supervision and success rate of weight reduction in children trying themselves. The fourth aim was to map the problems of cooperation of a nurse with parents and school in treatment of a child with obesity. We used a qualitative research method in the research part of the thesis. The questioning method by means of semi structured interview was applied. Three research samples were prepared for the research purposes. The first research sample consisted of 10 nurses working in paediatrician practitioner surgeries in Benešov District. The second research sample consisted of 10 persons intentionally chosen from among parents of children with obesity that are trying to reduce the weight of their children themselves or under assistance of an obesity specialist. The children were of school and pre-school age. The third research sample consisted of 10 paediatrician practitioners practicing in Benešov District. Open-coding technique paper and pencil method was applied on interview processing. A document analysis was used for the mapping of the services in Benešov District and the whole Central Bohemia Region. Six research questions were set: 1. What are the possibilities of specialist help to obese children? 2. Are parents willing to help their obese children with overweight reduction? 3. Do parents of obese children also have problems with overweight? 4. What experience do nurses from paediatrician practitioner surgeries have with care about obese children? 5. What does cooperation between parents and a nurse from a paediatrician practitioner surgery looks like? 6. How does a nurse working in a paediatrician practitioner's surgery cooperates with the school? The thesis conclusion shows that the problem of children obesity is not just the matter of Benešov District, but it is a global problem, it is urgent and has an increasing trend.

Indiana University-Purdue University Indianapolis (IUPUI) / Purpose: Obesity is a growing public health problem and the second most preventable cause of death in the US. Obesity has been linked as a risk factor for several cancers. However, there are limited studies that have examined the roles of metabolic syndrome (MetS) and C-reactive protein (CRP), as well as change in body composition from early adulthood to late adulthood on the risk of cancer. The overall objective of this dissertation was to determine the association of obesity and obesity-related markers with breast and colorectal cancer occurrence and mortality. Methods: Three datasets were used. The first study used 4,500 asymptomatic adults who were surveyed during a colorectal cancer screening study. The second study was based on the National Health and Nutrition Examination Survey (NHANES) 2005-2010. The dataset had 172 breast cancer survivors and 2,000 women without breast cancer. The last manuscript resulted from the NHANES follow-up study (NHANES III). A total of 120 cancer deaths from breast and colorectal deaths were identified from 10,103 women aged 18 years or older. Results: Overall, obesity and obesity related markers were associated with breast and colorectal cancer occurrence and mortality. BMI change and WC change were positively associated with increased risk of advanced colorectal neoplasia (AN). WC measures (both static and dynamic) were generally a better predictor of AN compared to BMI. In the second study involving breast cancer survivors, neither MetS nor CRP were associated with having a breast cancer diagnosis. Also, none of the individual components of MetS (WC, Triglycerides, HDL, fasting blood glucose and blood pressure) were associated with a breast cancer diagnosis. In the last study, MetS was associated with increased risk of mortality from obesity-related cancers. In addition, all components of MetS, except dyslipidemia, were associated with increased risk of mortality for the obesity-related cancers. Conclusion: Obesity expressed in terms of BMI and WC, or their change, MetS and CRP are important factors in regard to the occurrence, survivorship and mortality of breast and colorectal cancer. The results of this research underscore the importance of maintaining a healthy weight.