The overall aim of this thesis is to investigate if the somatic comorbidity and increased mortality among persons with psychiatric disability (residents in supported housing facilities) can be influenced. The thesis comprises four papers. Paper I describes the lived experience of health and body. Papers II and III examine the effects of a lifestyle programme on physiological markers (II) and on psychological and quality of life parameters (III). Paper (IV) illustrates the meaning of participating in a life style programme. The data in Papers I and IV comprises narrative interviews with residents (n=11). The studies in Papers II and III are focused on residents and were carried out with a randomized design. The randomization was performed on a group level (supported housing facility). The 12 month intervention consisted of study circles with a theoretical and practical application of dietary information and physical activity for two hours, on a twice weekly basis under the supervision of a study circle leader. The controls were offered an aesthetic study circle and met once a week. The data in Paper II comprises physiological quantitative data from both residents (n=41) and staff (n=41) and in Paper III questionnaires on symptoms and quality of life completed only by residents (n=41). The data was analysed with Qualitative description (I), Phenomenological-hermeneutics (IV), and for papers II and III relevant statistical calculations were used. Health is described in paper I as “having a life as others have” and discloses the losses of important life domains (family, work, security) and the experiences of being deviant and stigmatized. Health is described as “absence of psychological and physical problems” and its hampering effects on quality of life and self-esteem. Health is understood as a phenomenon that could “be influenced by one self”, and there is an insight that health is manageable. Participating in a life style intervention (paper II) meant a significant improvement in risk factors for metabolic syndrome among the residents in comparison with controls. No differences were seen on weight, BMI and improved physical capacity. In paper III a significant positive increase in the Sense of Coherence compared to controls was seen. However no effect was seen on quality of life, psychosocial function or on reduction of symptoms in comparison with controls. Participating in a lifestyle intervention can be understood as the gaining of insights that health can be improved and that the daily life is partly given a changed content (paper II). The participation is also described as meaning an increased sense of closeness and equality in relation to the staff and sometimes a painful insight of their life situation. Participating is also described as entailing a hope that one’s life situation can be affected. In summary this thesis shows that there is some possibility of influencing the physical health (reduced risk of metabolic syndrome) among persons with psychiatric disability by participating in a 12 month intervention programme. The intervention does not show any effects on measures such as quality of life, psychosocial function and presence of symptoms. However, the participants describe that the participation had a meaning in a number of respects. This is a finding that is confirmed by the positive change in sense of coherence. The need to develop preventive care for persons with psychiatric disability and the importance of monitoring the treatment with neuroleptics and its side effects on physical health is an important clinical implication. Furthermore the importance of the responsibility of the care staff is emphasized as well as the importance of supporting a change in lifestyle.

Insulin resistance is an early marker of Type II diabetes. Excessive lipid accumulation in muscle and liver leads to insulin resistance, and lowering tissue lipids causes an enhancement of insulin action. The enzyme AMP-activated protein kinase (AMPK) is activated when cellular energy levels are compromised, such as during exercise; this enhances fuel oxidation and inhibits energy consuming processes. The hypothesis in this thesis was that activating AMPK in a lipid-induced insulin resistant state leads to tissue lipid reduction and improved insulin sensitivity. Insulin resistant high-fat fed (HF-) rats were administered 5-aminoimidazole-4-carboxamide-1-??-D-ribofuranoside (AICAR), a specific AMPK activator. During an euglycaemic hyperinsulinaemic clamp performed 24h later, HF-rats showed increased whole body, muscle and liver insulin action, independent of changes in PKB-phosphorylation. The liver had reduced triglycerides, malonyl-CoA and increased IkB-a content. A lowering of muscle malonyl-CoA was consistent with conditions favouring increased lipid utilisation. Normal, chow-fed rats also showed improved insulin action post-AICAR. Further studies showed that basal glucose uptake was not increased 24h after AICAR, suggesting that AMPK activation had caused an increase in insulin sensitivity. Diacylglycerols and triglycerides, but not ceramides, were reduced in the liver of AICAR treated HF-rats, suggesting lipid reduction as a likely mediator of enhanced liver insulin action. These lipid species were not reduced in muscle. AICAR administration to HF-rats lowered plasma glucose and fatty acids (FA) acutely, probably due to increased muscle glucose uptake and FA oxidation. Glycogen was reduced in liver and increased in muscle, suggesting glucose mobilisation from liver to muscle. Adrenergic blockade excluded the sympathetic nervous system in the acute AICAR effects. AMPK was activated in white muscle and liver of HF-rats immediately after AICAR, the same tissues that exhibited later improved insulin sensitivity. Tracer technologies used to investigate glucose and lipid fluxes showed that AMPK activation in white muscle simultaneously increased both glucose and FA uptake and their metabolism, with glucose also being stored as glycogen. The liver showed lower lipid synthesis, consistent with reduced liver lipid accumulation observed 24h post-AICAR. In conclusion, these results suggest that activation of AMPK leads to selective tissue lipid reduction and improved insulin action, and is a potential target for the treatment of insulin resistance and type II diabetes.

No description available.

No description available.

Submitted by Claudete Queiroz (claudete.queiroz@icict.fiocruz.br) on 2015-10-19T13:11:29Z No. of bitstreams: 1 danielle_mattos_iff_dout_2014.pdf: 778720 bytes, checksum: 2f7d6d9a8edb3b26e86ea3c7462e9fbd (MD5) / Approved for entry into archive by Claudete Queiroz (claudete.queiroz@icict.fiocruz.br) on 2015-10-19T13:11:48Z (GMT) No. of bitstreams: 1 danielle_mattos_iff_dout_2014.pdf: 778720 bytes, checksum: 2f7d6d9a8edb3b26e86ea3c7462e9fbd (MD5) / Made available in DSpace on 2015-10-19T13:11:58Z (GMT). No. of bitstreams: 1 danielle_mattos_iff_dout_2014.pdf: 778720 bytes, checksum: 2f7d6d9a8edb3b26e86ea3c7462e9fbd (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil. / Considerando que a faixa etária de 5 a 9 anos corresponde a 11% do total de brasileiros, e o crescente aumento da obesidade na infância, há um número expressivo de indivíduos que, no futuro, estarão propensos a desenvolver alterações cardiometabólicas e, em última análise, sobrecarregar os serviços de saúde, comprometer a força de trabalho e elevar o custo da saúde pública no país. Assim, é de interesse para a saúde pública o estabelecimento de medidas simples para identificação precoce destes indivíduos. O objetivo do estudo foi verificar a associação entre medidas de localização da gordura abdominal e os fatores de risco cardiometabólicos em crianças de 6 a 9 anos em Vitória, ES. Avaliou-se a circunferência da cintura (CC), a relação cintura estatura (RCE), o índice de conicidade (IC) e a relação dobra cutânea subescapular e tricipital (RDC). Os componentes da SM foram os propostos pela International Diabetes Federation (IDF) com pontos de corte ajustados para a idade. Aplicou-se o modelo de regressão logística multinomial. A prevalência de SM foi 2% e de excesso de peso 38,4%. A presença de pelo menos um componente da SM foi detectada em 35,8%. O IC mostrou-se um preditor independente na identificação precoce de pelo menos um componente da SM, a CC foi preditora da presença de dois ou mais componentes da SM, independente do sexo. A avaliação de medidas antropométricas da gordura abdominal na população infantil podem sugerir o risco potencial da presença de alterações cardiometabólicas isoladas e simultâneas prevenindo as doenças cardiovasculares, que são a maior causa de morte no Brasil. / Considering that the age group 5-9 years old corresponded to 11% of Brazilians, and the increasing childhood obesity, there are a significant number of individuals in the future are likely to develop cardiometabolic alterations and ultimately , overburden health services, compromising the workforce and raise the cost of public health in the country. Thus, it is of interest to public health establishment of simple measures for early identification of these individuals. The aim of the study was to investigate the association between abdominal fat measures and cardiometabolic risk factors in children aged 6 to 9 years in Vitoria, ES. We evaluated the waist circumference (WC), waist to height (WH), the conicity index (CI) and the relationship subscapular and triceps skinfold (RDC). Metabolic Syndrome (MS) components were the International Diabetes Federation (IDF) proposed with cut-off points adjusted for age. We used the model of multinomial logistic regression. The prevalence of MS was 2% and 38.4% overweight. The presence of at least one component of the metabolic syndrome was detected in 35.8%. The IC was found to be an independent predictor of early identification of at least one component of MS and WC was predictive of the presence of two or more components of MS, regardless of sex. The evaluation of anthropometric measures of abdominal fat in children may suggest the potential risk of the cardiometabolic alterations preventing cardiovascular diseases, which are the leading cause of death in Brazil.

La séquence des événements moléculaires engendrés par des perturbations de signaux externes qui peuvent affecter les horloges circadiennes, et générer des pathologies restait peu connue. Durant ma thèse, j’ai démontré au niveau moléculaire, comment déplacer l’horaire de l'alimentation chez la souris de la phase active à la phase de repos, altère le métabolisme à la suite d’une hypoinsulinémie durant la phase active, ce qui provoque une activation de PPARα qui reprogramme le métabolisme et l'expression de RevErbα et qui de ce fait décale l’horloge de 12h dans les tissus périphériques. Notamment, l’absence de PPARα dans le noyau suprachiasmatique empêche le décalage de l’horloge centrale. Ainsi, les phases d’activité et de repos contrôlées par l’horloge centrale ne sont plus alignées avec l'expression des gènes contrôlée par les horloges périphériques. Ce non-alignement crée un syndrome métabolique similaire à celui observé chez des individus soumis à des horaires de travail décalés. / The sequence of molecular events through which alterations in externals cues may impinge on circadian clocks, and generate pathologies, was mostly unknown. During my thesis work, I have molecularly deciphered, how switching feeding in mice, from the “active” to the "rest" phase [Restricted Feeding (RF)] , alters the metabolism through hypoinsulinemia during the “active” phase, leading to increased PPARα activity, thereby reprograming both metabolism and RevErbα expression and leads to a 12h circadian clock-shift in peripheral tissues.Most notably, the lack of PPARα expression in the suprachiasmatic nuclei (SCN) prevents a shift of the central clock. Therefore, the “active” and “rest” phases controlled by the SCN clock and gene expression controlled by the peripheral circadian clocks are misaligned. Most interestingly, this misalignment generates a metabolic syndrome-like pathology, similar to that associated with shiftwork schedules.

No description available.

Introdução: As doenças cardiovasculares constituem a principal causa demorbimortalidade nacional. Nesse sentido realizou-se estudo com o objetivo de caracterizar o perfil para riscos cardiovasculares em motoristas profissionais de transporte de cargas que trafegam pela Br-116. Casuística e Método: Estudo transversal, descritivo e exploratório com 258 motoristas profissionais de transporte de cargas com obtenção de informações socioeconômicas; avaliações antropométricas: índice de massa corporal (IMC), circunferência abdominal e medida da pressão arterial; realização de exames laboratoriais: triglicérides, colesterol total e frações, proteína C reativa e creatinina. Analisou-se o risco para doenças cardiovasculares pelo Escore de Risco de Framingham, consumo de bebidas alcoólicas pelo Alcohol Use Disorders Identification-AUDIT, distúrbios psiquiátricos comuns pelo Self Report Questionnaire-SRQ-20, Síndrome Metabólica e angina pectoris pelo Teste de Rose. Os dados foram processados no sistema SPSS v.7.5. O nível de significância adotado foi p<0,05, utilizou-se análise univariada e multivariada. Resultados: A caracterização os motoristas estudados mostrou idade 37,5±10,1 anos, 91% de etnia branca, renda mensal 1.431,3±644,4 reais, 19% tabagistas, 55% referiram ingestão de bebidas alcoólicas, 74% não realizavam atividade físicas, 14% relataram uso de medicamentos inibidores do sono, tempo profissão de 14±10 anos e percorriam 782,9±229,6 km/dia, dirigiam 10 horas por dia e repousavam 06 horas diárias. Verificou-se pelos dados antropométricos que 46% tinham sobrepeso, 36% obesidade e 58% circunferência abdominal alterada (_94 cm). Os exames laboratoriais mostraram 33% com nível de colesterol total _ 200mg/dL, 10% LDL-c _ 160 mg/dL; HDL-c < 40 mg/dL 23%, triglicérides acima de 150 mg/dL 38%, glicemia _ 110mg/dL 7% e proteína C reativa > 0,5 mg/dL 19%, creatinina >1,5 mg/dL 1%. A prevalência da hipertensão arterial foi de 37% e da Síndrome metabólica 24%. O Questionnaire Rose foi positivo em 8,0% dos motoristas, Escore de Risco de Framingham médio/alto em 9%, presença de distúrbios psiquiátricos comuns em 33% e AUDIT 16% no escore que sugere intervenção e aconselhamento. A análise de regressão logística indicou associação independente para as seguintes variáveis (OD Odds ratio, IC intervalo de confiança a 95%): 1-Síndrome Metabólica: IMC (OR=1,40 IC 1,192-1,661); hábito de verificar o colesterol total (OR= 0,102 IC 0,017-0,589); e escore de risco de Framingham médio/alto (OR= 26,389 IC 2,520-276,374). 2-Hipertensão arterial: IMC (OR=1,183 IC 1,065-1,314); glicemia (OR=1,039 IC 1,004-1,076); e hábito de ingerir medicamento para inibir o sono (OR= 0,322 IC 0,129-0,801). 3- Colesterol Total (_ 200 mg/dL): LDL-c (OR=1,157 IC 1,100-1,216);triglicérides (OR=1,012 IC 1,004-1,021) 4- Glicemia (_ 110 mg/dL): IMC (OR=1,153 IC 1,024-1,298); maior tempo de profissão (OR=1,154 IC 1,057-1,259) 5-Proteína C reativa (>0,5 mg/dL): escore de risco de Framingham médio/alto (OR=4,692 IC 1,912-11,515). Conclusão: Verificou-se presença expressiva de fatores de risco cardiovasculares, nesse sentido os profissionais de saúde devem implementar estratégias para estimular mudanças de estilos de vida nos motoristas de transporte de cargas, visando a prevenção primária e secundária / Introduction: Cardiovascular diseases are the main cause of morbidity and mortality in Brazil. Therefore, a study aiming at characterizing the cardiovascular risk profile observed in professional truck drivers who work on Highway Br-116 was carried out. Population and Method: An exploring, descriptive and transversal study with 258 professional truck drivers, social economical information, both body mass index (BMI) and waist circumference evaluations, blood pressure measurement, as well as laboratory test performance: triglycerides, total and fraction cholesterol, and C reactive protein. The risk for cardiovascular diseases was assessed by Framingham scores; alcohol intake by Alcohol Use Disorders Identification-AUDIT; common psychiatric disorders by Self Report Questionnaire-SRQ-20; and angine pectoris by Rose´s test Data were processed in the SPSS system v.7.5, considering that the significance level adopted was 0,05, and univaried and multivaried analyses were used. Results: The characterization of the drivers studied revealed age of 37.5±10.1 years, 91% of them were white, monthly income 1.431,3 ± 644,4 reais (Brazilian currency), 19% were smokers, 55% referred alcohol intake, 74% did not make physical exercises, 14% referred using sleeping inhibitor drugs, professional time 14±10 years and used to drive 782,9±229,6 Km/day. It was observed that 46% of them were overweight and 36% were obese and 58% had altered waist circumference (_ 94 cm) by the anthropometric data. The lab tests showed 33% with total cholesterol level _200 mg/dL, 10% LDLc _160 mg/dL, HDL-c <40 mg/dL 23%, triglycerides over 150 mg/dL 38%, glycemy _110mg/dL 7%, and C reactive protein >0.5 mg/dL 19%. The prevalence of hypertension was 37% and of Metabolic Syndrome, 24%. Rose’s test was positive for 8% of the drivers, Medium/High Framingham scores for 9%, presence of common psychiatric disturbs in 33% and 16% with AUDIT score suggesting intervention and advisory. The logistical regression analysis indicated independent association for the following variables: (OR Odds ratio, CI confidence interval at 95%): 1- Metabolic Syndrome: BMI (OR=1,40 CI 1,192-1,661); the habit of checking the total cholesterol (0,102 IC 0,017-0,589); Medium/high Framingham score (OR=26,389 IC 2,520-276,374); 2-Hypertension: BMI (OR=1,183 IC 1,065-1,314); glycemy (OR=1,039 IC 1,004-1,076); the habit of taking sleeping pills (OR=0,322 IC 0,129-0,801). 3- Total Cholesterol (_ 200 mg/dL): LDL-c (OR=1,157 IC 1,100-1,216); triglycerides (OR=1,012 IC 1,004-1,021). 4- Glycemy (_ 110 mg/dL): BMI (OR=1,153 IC 1,024-1,298); professional time (OR=1,154 IC 1,057-1,259). 5- C reactive protein (>0,5 mg/dL): Medium/high Framingham score (OR=4,692 IC 1,912-11,515). Conclusion: It was observed an expressive presence of cardiovascular risk factors. Therefore health professionals should implement strategies to stimulate changes in truck drivers’ lifestyle, aiming at primary and secondary prevention

THESIS SUBMITED IN FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF THE DEGREE OF DOCTOR OF TECHNOLOGY OF BIOMEDICAL TECHNOLOGTY IN THE FACULTY OF HEALTH AND WELLNESS SCIENCES AT THE CAPE PENINSULA UNIVERSITY OF TECHNOLOGY SUPERVISORS: PROF T.E. MATSHA PROF R.T. ERASMUS DR A. ZEMLIN SUBMITED DECEMBER 2013 / Introduction: Cardiovascular diseases (CVD) have become the leading cause of morbidity and mortality amongst the global population. Originally thought to be a health burden of high income countries, the prevalence is rapidly increasing in developing countries. For example, in 2008, an estimated 17.3 million died from CVD, and 80% of these (13.8 mil) were from low to middle income countries. Epidemiological data on CVD in Africa is scanty and of poor quality and national vital registration is available in only 5% of Africa’s 53 countries. Furthermore, data on CVD risk amongst the South African population and specifically the mixed ancestry community is poorly described. The increasing global population of people with CVD has been largely attributed to increasing rates of determinants and risk factors which include obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (DM) and chronic kidney diseases (CKD). The prevalence of DM in South Africa is known to be on the rise with more affected communities being South African Asians followed by coloureds. Aims and objectives: The aim of this study was to determine the CVD risk profile of the Bellville South community during a baseline and three year follow-up study, by assessment of known risk factors, MetS, type 2 DM, obesity and CKD. Methods: Participants for this study were drawn from an urban community of the Bellville South suburb of Cape Town. At baseline (January 2008 and March 2009) 946 individuals aged 16 to 95 participated. All participants received a standardized interview and physical examination during which anthropometric measurements were performed three times and their average used for analysis: weight (kg), height (cm), waist (cm) and hip (cm) circumferences. Body Mass Index (BMI) was calculated as weight per square metre (kg/m2). A blood sample was obtained from all participants after an overnight fast for the determination of biochemical profiles: glucose, glycated haemoglobin, creatinine, total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides and low density lipoprotein cholesterol (LDL-C) which was calculated using Friedewald’s formula. Kidney function test was assessed through estimated glomerular filtration rate (eGFR) using the cockcroft-Gault and MDRD equations. Blood pressure was measured according to the World Health Organisation (WHO) guidelines. Participants with no history of doctor diagnosed DM underwent a 75 g oral glucose tolerance test as recommended by the WHO. Metabolic syndrome was determined using JIS, NCEP ATPIII and IDF criteria. The follow-up examination was conducted in 2011 (3 years from vii baseline) using similar procedures. A total of 198 participants formed the follow-up cohort whose measurements were compared to those of the baseline. Finally, the prediction and processes/progression of the risk factors were determined. Results: At both baseline and follow-up studies, females had a higher BMI compared to their male counterparts. The crude prevalence of type 2 DM, including the previously diagnosed type 2 DM was 28.59% (age-adjusted = 33.5%, 95%CI: 30.01 – 36.92), and that of undiagnosed type 2 DM was 17.8% (age-adjusted = 12.4%, 95%CI: 9.8 – 14.8). The overall prevalence of CKD was 28.7% (269) and was higher in females (31.4%) compared to 20.2% in males. MetS was present in 46.5% of the participants. Gender-specific prediction for CVD risk calculated using the 30-year CVD interactive risk calculator showed that high CVD risk was present in normoglycaemic and younger subjects (under 35 years). At follow-up, the cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of MetS. Between baseline and 3-year evaluation glomerular filtration rate (eGFR) increased by 8.7 ml/min (95% confidence interval: 6.9-10.7), reflecting variables trajectories across baseline strata of kidney functions. Conclusion: Given the findings of this study and the estimated increases in the determinants and risk factors of CVD in the mixed ancestry population of South Africa this trend may continue to worsen if current trajectories do not change.

Hypertension is a major risk factor for cardiovascular (CV) disease, and patients with primary aldosteronism (PA) - the most common endocrine cause of hypertension - have a higher incidence of CV complications. The aim of this study was to evaluate the incidence of metabolic differences and organ complications - kidney, heart and blood vessels damage in patients with essential hypertension (EH), PA and its most common forms - idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA). We found a higher incidence of metabolic syndrome and a higher incidence of metabolic abnormalities in IHA compared to APA - higher prevalence of metabolic syndrome, higher levels of triglycerides and lower levels of HDL cholesterol and thereby a higher cardiometabolic risk. Metabolic profile of patients with IHA is similar to EH in contrast to APA. Arterial stiffness was expressed as pulse wave velocity (PWV), in central arteries as carotid-femoral PWV and at peripheral level as femoral-ankle PWV. Patients with PA with comparable levels of blood pressure (BP) have higher stiffness of central elastic and peripheral muscular arteries than patients with EH. The main predictor of impaired peripheral arterial stiffness is the plasma aldosterone level. Patients with IHA have higher central arterial...