Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-20T13:14:40Z No. of bitstreams: 1 hussenmachado.pdf: 992962 bytes, checksum: 6f5d0b2997eefc4508c4d64ee629e6bc (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-02T11:21:23Z (GMT) No. of bitstreams: 1 hussenmachado.pdf: 992962 bytes, checksum: 6f5d0b2997eefc4508c4d64ee629e6bc (MD5) / Made available in DSpace on 2016-07-02T11:21:23Z (GMT). No. of bitstreams: 1 hussenmachado.pdf: 992962 bytes, checksum: 6f5d0b2997eefc4508c4d64ee629e6bc (MD5) Previous issue date: 2012-12-14 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Introdução: O tratamento da hipertensão arterial (HA) em indivíduos com síndrome metabólica (SM) é um desafio, uma vez que terapias não medicamentosas são de difícil implementação e o tratamento farmacológico ideal não está totalmente estabelecido.Objetivo: O presente trabalho objetivou avaliar o bloqueio do sistema renina angiotensina aldosterona (SRAA) na pressão arterial (PA), na função e na morfologia renais em modelo experimental de SM, induzida por dieta hiperlipídica.Material e métodos: Ratos Wistar receberam ração hiperlipídica a partir da quarta semana de vida, por 20 semanas. Os grupos tratados receberam Losartana (10mg/kg/dia), Espironolactona (40mg/Kg/dia) ou quercetina (10mg/kg/dia), por gavagem, a partir da oitava semana de vida. Avaliou-se semanalmente o peso corporal e a PA de cauda por pletismografia. Ao final do experimento, foram realizados testes orais de tolerância à glicose, perfil lipídico, clearance de creatinina, medida direta da PA e análise morfométrica de área e volume glomerular.Resultados: A administração de dieta hiperlipídica se associou ao desenvolvimento de SM, caracterizada por acúmulo central de gordura, hipertensão arterial, hiperglicemia e hipertrigliceridemia. Nesse modelo, não foram observadas alterações da histomorfometria glomerular. O bloqueio do receptor AT1 da angiotensina II preveniu o desenvolvimento da HA. O bloqueio mineralocorticóide não apresentou eficácia anti-hipertensiva, porém se associou à redução da gordura abdominal. A quercetina, por sua vez, não alterou de forma significante o perfil nutricional, metabólico e pressórico dos animais. Conclusão: Ratos Wistar alimentados com dieta hiperlipídica desenvolveram Síndrome Metabólica, porém não foram observadas alterações morfológicas e funcionais renais. / Introduction: The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. Objectives: The present study had as objective to evaluate the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. Material e methods: Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan (10mg/Kg/day), Spironolactone (40mg/Kg/day) or Quercetin (10mg/Kg/day) from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. Results: The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. Quercetin, in turn, does not significantly alter animals nutritional, pressure and metabolic profile. Conclusion: Wistar rats fed high fat diet developed metabolic syndrome but no changes were observed morphological and functional kidney.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-15T18:14:17Z No. of bitstreams: 1 alexamagalhaesdias.pdf: 604087 bytes, checksum: 8ea5c8f9051eac24c5b6b2dd4138c20c (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:20:56Z (GMT) No. of bitstreams: 1 alexamagalhaesdias.pdf: 604087 bytes, checksum: 8ea5c8f9051eac24c5b6b2dd4138c20c (MD5) / Made available in DSpace on 2016-09-26T20:20:56Z (GMT). No. of bitstreams: 1 alexamagalhaesdias.pdf: 604087 bytes, checksum: 8ea5c8f9051eac24c5b6b2dd4138c20c (MD5) Previous issue date: 2010-08-29 / Muitas evidências indicam que há uma relação entre a periodontite e a síndrome metabólica. Ao mesmo tempo, para muitos autores a doença periodontal pode contribuir para o desenvolvimento de doenças crônicas, dentre elas a obesidade, o diabetes e doenças cardiovasculares. Através de um estudo transversal de caso controle, procurou-se, avaliar as condições periodontais e os níveis séricos da interleucina-6 em indivíduos portadores de síndrome metabólica. Foram selecionados vinte pacientes com síndrome metabólica (caso) e dez pacientes saudáveis com doença periodontal (controle). Todos os indivíduos foram submetidos a uma avaliação periodontal e a coleta de sangue para pesquisa dos níveis de IL-6, triglicérides, HDL-C e glicemia. Foram realizadas aferições da pressão arterial e dos índices antropométricos. Verificou-se que as condições periodontais de indivíduos saudáveis foram sensivelmente piores no grupo controle. Houve uma prevalência de 100% de periodontite no grupo caso. Foi observado, no grupo portador de síndrome metabólica, correlações entre a perda de inserção clínica e a glicemia em jejum e, também entre a IL-6 e os níveis de HDL-C. No grupo controle não foram observadas correlações entre os parâmetros periodontais e os componentes da síndrome metabólica. Porém a IL-6 foi positivamente relacionada a perda de inserção periodontal. Os resultados sugerem que a perda de inserção clinica pode ter influência sobre os níveis glicêmicos de portadores de síndrome metabólica. Além disso, a alta prevalência de periodontite entre esses pacientes dão suporte a teoria da possível relação entre a doença periodontal e a síndrome metabólica. / Many evidences indicate that there is a relationship between periodontitis and metabolic syndrome. At the same time, many authors affirm that the periodontal disease can contribute for the development of systemic alterations as obesity, diabetes and heart diseases. Through a cross-sectional case control study, we sought to assess the periodontal condition and serum levels of interleukin-6 in individuals with metabolic syndrome. We selected twenty patients with metabolic syndrome (case) and ten healthy patients with periodontal disease (control). All participants underwent a clinical periodontal examination and venous blood samples were obtained for research in the levels of interlekin-6, tryglicerides, HDL-C and glucose. We performed measurements of pressure and anthropometric indices. It was found that the periodontal conditions in healthy subjects were feelingly worse in the control group. There was 100% prevalence of periodontitis in the case group. Was observed in the group with metabolic syndrome, correlations between clinical attachment loss and fasting glucose, and also between IL-6 levels and HDL-C. In the control group no correlation between periodontal parameters and components of metabolic syndrome. However, IL-6 was positively related to clinical attachment loss. Results suggest that clinical attachment loss may have influence on glucose levels in patients with metabolic syndrome. Moreover, the high prevalence of periodontitis in these patients support the theory of a possible relationship between periodontal disease and metabolic syndrome.

Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-18T22:10:38Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Aline_Longo.pdf: 1263882 bytes, checksum: 3cfecd84c4beeee8747151fba3894772 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-18T22:43:49Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Aline_Longo.pdf: 1263882 bytes, checksum: 3cfecd84c4beeee8747151fba3894772 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-18T22:43:55Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Aline_Longo.pdf: 1263882 bytes, checksum: 3cfecd84c4beeee8747151fba3894772 (MD5) / Made available in DSpace on 2018-05-18T22:43:55Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Aline_Longo.pdf: 1263882 bytes, checksum: 3cfecd84c4beeee8747151fba3894772 (MD5) Previous issue date: 2016-07-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / As doenças cardiovasculares, além de representarem a principal causa de morte no Brasil e no mundo, podem gerar doentes crônicos. A prevenção secundária de pacientes com tal comorbidade torna-se importante, e o estudo de fatores prognósticos auxilia em tal conduta. O objetivo deste trabalho foi avaliar fatores prognósticos de doença cardiovascular e investigar possíveis associações entre eles, em uma amostra de pacientes com aterosclerose manifesta do município de Pelotas/RS. Trata-se de estudo transversal, aninhado a um ensaio clínico randomizado, com dados dos pacientes do centro colaborador de Pelotas/RS. Foram coletadas variáveis clínicas, antropométricas, bioquímicas, sociodemográficas, alimentares e qualidade de vida relacionada à saúde. A análise estatística foi realizada através dos programas Graph Pad® e Stata®. A maioria da amostra era do sexo masculino, idosa, pertencente à classe econômica C, estudou até o ensino fundamental, era fumante ou ex-fumante e possuía excesso de peso, doença arterial coronariana, hipertensão, dislipidemia e histórico familiar de doença cardiovascular. Quanto ao consumo alimentar (n=74), classificado de acordo com o grau de processamento, o grupo de alimentos que mais contribuiu com o consumo calórico diário foi o in natura/minimamente processados (50,9%), seguido pelo consumo de alimentos ultraprocessados (35,1%), processados (11,1%) e ingredientes culinários processados (2,9%). Possuir excesso de peso e ser fumante/ex-fumante estiveram positivamente associados à pontuação da síndrome metabólica, com um acréscimo de 0,64 e 0,48 pontos, respectivamente (n=82). Com relação à qualidade de vida relacionada à saúde (n=70), o escore dos domínios de saúde física foi inferior ao escore de saúde mental (p<0,0001). Índice de massa corporal e circunferência da cintura estiveram negativamente associados à qualidade de vida relacionada à saúde, enquanto que o consumo de fibras dietéticas, potássio e magnésio apresentaram associação positiva. Na amostra analisada, o consumo de alimentos processados/ultraprocessados mostrou-se elevado, visto que foi quase igual ao consumo de alimentos in natura/minimamente processados. Fibra dietética, potássio e magnésio, estiveram positivamente associados à qualidade de vida relacionada à saúde. Por outro lado, altos valores de circunferência da cintura e índice de massa corporal estiveram negativamente associados à qualidade de vida relacionada à saúde. Ademais, o índice de massa corporal elevado (excesso de peso) e tabagismo foram responsáveis por aumentarem a pontuação da síndrome metabólica. Dessa forma, a prevenção secundária dos pacientes analisados deve contemplar intervenções para um estilo de vida mais saudável, principalmente voltadas à alimentação adequada e à manutenção do peso na faixa da normalidade. / Cardiovascular diseases, besides representing the leading cause of death in Brazil and worldwide, can lead to chronic conditions. Secondary prevention of patients with this comorbidity becomes important, and the study of prognostic factors helps in such conduct. The aim of this work was to evaluate prognostic factors of cardiovascular diseases and to investigate possible associations between them, in a sample of patients with established atherosclerosis disease, in Pelotas/RS. Cross-sectionals studies, nestled to a randomized clinical trial, were performed, with data of the collaborating site of Pelotas/RS. Clinical, anthropometric, biochemistry, sociodemographic, alimentary and health-related quality of life variables were collected. Statistical analyzes were carried out in Graph Pad® e Stata®. The majority of the sample was men, elderly, from economic level C, studied until elementary school, was former or current smoker and had overweight, coronary artery disease, hypertension, dyslipidemia and familiar history of cardiovascular diseases. About alimentary consumption (n=74), classified according to the degree of processing, the group that most contributed to caloric consumptio was unprocessed/minimally processed foods (50.9%), followed by ultra-processed (35.1%), processed (11.1%) and processed culinary ingredients (2.9%). Overweight and being current/former smoker were positively associated to the pontuation of metabolic syndrome, with an increase of 0.64 and 0.48 points, respectivetly (n=82). Regarding health-related quality of life (n=70), the score of physical health domains was lower than the mental health (p<0.0001). Body mass index and waist circumference were negatively associated to health-related quality of life, whereas the consumption of dietary fiber, potassium and magnesium presented a positive association. In the analysed sample, alimentary consumption across the degree of processing foods was elevated, since the consumption of processed/ultra-processed foods was almost the same of unprocessed/minimally processed foods. Dietary fiber, potassium and magnesium were positively associated to health-related quality of life. On the other hand, high values of waist circumference and body mass index were negatively associated to health-related quality of life. Moreover, elevated body mass index (overweight) and tobacco use were identified as risk factors that increase the pontuation of metabolic syndrome. Thus, the secondary prevention of patients analysed must contemplate interventions to an healthier lifestyle, mainly focused to an adequate diet and to the maintenance of a proper weigh.

Background: Obesity has become one of our times most endemic disease on a global scale and changes to lifestyle is the most cost-effective way to treat patients, when the cost for healthcare related treatment is staggeringly high for obesity and sequela diseases NAFLD, diabetes typ 2, dyslipidaemia and metabolic syndrome.The problem with this remedy is that it requires work and dedication. But changes require hard work, and in this patient group- low compliance, weight gain after treatment, dropping out of programs and small desire to change are the most common problems. Motivational studies report that readiness in obese patients is low and the best way to help patients to move forward is by motivational conversations. The obesity sequela disease NAFLD is an asymptomatic disease it displays no symptoms until very late stages. Therefore it’s a problem to get patients make the patient understand his illness and the seriousness of it. Aim: This literature work was aimed at investigating compliance in lifestyle changes in obese subject and to see if close contact with healthcare staff affected the achieved results. Method: In this literature study, the databases Pubmed, Science Direct, Medline and Sportdiscus were used to find information. Article inclusion criteria were that the articles were not older than 10 years and were in English. Result: Frequent and regular contacts between participants and professional staff provided good results both with regard to weight loss, biochemical response, and the participants' willingness to change. Also it shows that return visits at least every three months will improve weight loss if the participant is motivated to implement a change to lifestyle. Conclusion: Overall, this literature study shows the difficulties with lifestyle changes in people with obesity and sequela NAFLD. Close contacts of the patients with healthcare staff has proven to have a positive impact on treatment compliance, but there are other lifestyle difficulties in these patient groups which hamper compliance.

Les ressources marines constituent un réservoir considérable de substances actives, en particulier, de peptides bioactifs appelés cryptides. Les cryptides, qui sont initialement dissimulés au cœur des protéines, sont libérés lors de la digestion ou lors de procédés protéolytiques industriels. Ces cryptides pourraient procurer des bienfaits physiologiques ou assurer une protection contre des pathologies telles que celles du syndrome métabolique. Dans ce contexte, nous nous sommes intéressés à l’action de certains cryptides marins sur des cibles impliquées dans l’hypertension, le diabète et l’obésité. Nous avons pu mettre en évidence que certains cryptides pouvaient cibler in vitro plusieurs facteurs de risques associés au développement des anomalies du syndrome métabolique. / Marine products represent an important source of active substances, in particular bioactive peptides called cryptides. Cryptides are hidden within the sequence of a parent protein and are released during digestion or industrial proteolytic processes. These cryptides could provide physiological benefit or protection against diseases such as those of metabolic syndrome. In this context, we investigated the action of some marine cryptides on hypertension, diabetes and obesity. We demonstrated that some cryptides can target in vitro several factors associated with the development of metabolic syndrome.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The sedentary lifestyle and a high fat diet are related with the emergence of metabolic syndrome (MS), which is represented by the cluster of risk factors such abdominal obesity, insulin resistance, dyslipidemia and hypertension. Nowadays, it is well known that both obesity and metabolic syndrome-related cardiovascular diseases are associated with oxidative stress and chronic low-grade inflammation. Considering that regular physical exercise may be considered one of the best non-pharmacological ways to MS prevention and treatment, few studies assessed the effects of moderate aerobic training (AT) alone on oxidative, inflammatory, anthropometric and functional parameters and quality of life in women with MS. Thus, it was investigated the effects of 15 weeks of AT on functional, anthropometric, biochemical profiles and the health-related quality of life (HRQOL) (manuscript 1) and the impact of 12 weeks of AT on body composition and systemic biomarkers of oxidative stress and inflammation in middle-aged women with MS (manuscript 2). Both inverventions comprised three weekly sessions of brisk walking and/or jogging in treadmills, with the training intensity being controlled by heart rate monitors. The 15-week AT decreased waist and hip circumferences, total cholesterol, low-density lipoprotein (LDL), thiobarbituric acid-reactive substances levels (TBARS) and myeloperoxidase and lactate dehydrogenase activities. Furthermore, it was observed an increasing in estimated maximal oxygen uptake and flexibility, albumin and high-density lipoprotein (HDL) levels and higher scores in physical functioning, role-physical, bodily pain, general health and social functioning domains in the HRQOL questionnaire. However, it was not found a simultaneous weight loss (manuscript 1). The 12-week AT provoked reductions in total body fat mass, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interferom-gamma (INF-γ), advanced oxidation protein products (AOPP) and TBARS levels. In this context, AT resulted in increased total body lean mass, interleukin-10 (IL-10) and total thiol groups content levels, even with the maintenance of nitrite and nitrate (NOx) levels (manuscript 2). Therefore, it was concluded that biochemical, anthropometric and quality of life improved-exercise related parameters are independent of weight loss and that the moderate aerobic training positively modulates inflammation and oxidative stress biomarkers and body composition in middle-aged women with MS. / O sedentarismo e as dietas hiperlipídicas estão relacionados com o surgimento da síndrome metabólica (SM), representada pela junção de fatores de risco, como obesidade abdominal, resistência insulínica, dislipidemia e hipertensão arterial. Atualmente, sabe-se que tanto a obesidade quanto as doenças cardiovasculares relacionadas com a presença da SM estão intimamente associadas ao estresse oxidativo e à inflamação crônica de baixo grau. Apesar de a prática regular de exercícios físicos ser considerada uma das melhores intervenções não farmacológicas para a prevenção e o tratamento da SM, poucos estudos analisaram os efeitos do treinamento aeróbico moderado (TA) isolado sobre parâmetros oxidativos, inflamatórios, antropométricos, funcionais e da qualidade de vida de mulheres com SM. Dessa forma, investigamos os efeitos de 15 semanas de TA sobre o perfil funcional, antropométrico, bioquímico e a percepção subjetiva da qualidade de vida (PSQV) (manuscrito 1) e o impacto de 12 semanas de TA sobre a composição corporal e marcadores sistêmicos de inflamação e de estresse oxidativo de mulheres de meia-idade com SM (manuscrito 2). Ambas as intervenções foram compostas por três sessões semanais de caminhadas rápidas e/ou corridas leves em esteiras, sendo que a intensidade prescrita do treinamento foi controlada através de monitores cardíacos. O TA de 15 semanas foi efetivo na diminuição das circunferências da cintura e do quadril, dos níveis de colesterol total, lipoproteínas de baixa densidade (LDL), de substâncias reativas ao ácido tiobarbitúrico (TBARS) e da atividade das enzimas mieloperoxidase e lactato desidrogenase. Além disso, observou-se um aumento da estimativa do consumo máximo de oxigênio e da flexibilidade, dos níveis de albumina e lipoproteínas de alta densidade (HDL) e maiores pontuações nos domínios de capacidade funcional, limitação por aspectos físicos, dor, estado geral de saúde e aspectos sociais do questionário relacionado à PSQV. Entretanto, não foi constatada uma concomitante redução ponderal (manuscrito 1). Doze semanas de TA provocaram redução da quantidade total de tecido adiposo, bem como dos níveis de interleucina-1 beta (IL-1β), interleucina-6 (IL-6), fator de necrose tumoral alfa (TNF-α), interferon-gama (INF-γ), produtos avançados de oxidação proteica (AOPP) e TBARS. Nesse contexto, ele causou aumento do conteúdo total de massa magra, dos níveis de interleucina-10 (IL-10) e tióis totais, apesar da manutenção dos níveis de nitritos e nitratos (NOx) (manuscrito 2). Assim, conclui-se que os benefícios sobre variáveis bioquímicas, antropométricas e a qualidade de vida oportunizados pela prática regular de exercícios aeróbicos não são dependentes da perda ponderal e que o treinamento aeróbico moderado modula positivamente marcadores de inflamação e estresse oxidativo e a composição corporal em mulheres de meia-idade com SM.

4 Abstract The prevalence of obesity and its related cardiometabolic complications in children remains high across the world. Obesity is a multifactorial disease caused by interaction between genes and environmental factors. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with obesity. A causal role of infection in the pathogenesis of obesity has also been considered, particularly the role of adenovirus 36 (Adv36). The aim of the Ph.D. thesis was to investigate the associations of obesity susceptibility loci (TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and Adv36 infection with obesity-related characteristics and complications in the Czech adolescent population. The results are described in eight publications, of which six are original papers and two are reviews. Studies were performed on a cohort of Czech adolescents recruited either from the general population (1,533 individuals from the epidemiological study) and from in-patient or outpatient weight management clinics (562 overweight/obese individuals underwent an intervention). The results demonstrated an association of TMEM18, SEC16B and FTO gene variants with obesity. Some variants of the genes involved in hypothalamic regulation of energy homeostasis − MC4R, BDNF, PCSK1 − were related to...

Abstract Metabolic syndrome is a constellation of metabolic abnormalities including abdominal obesity, glucose intolerance, insulin resistance, hypertension and dyslipidemia. Metabolic syndrome increases the risk of cardiovascular diseases and type 2 diabetes mellitus. A unifying pathophysiological mechanism behind these abnormalities has not been detected. The prevalence of cardiovascular diseases and type 2 diabetes mellitus is increasing all over the world. It is important to identify the factors contributing to these diseases. The aim of this thesis was to study how the peptide hormone resistin is associated with metabolic syndrome and find out whether intrauterine growth restriction predisposes to adverse changes in lipid and glucose metabolism and peptide hormones in a rat model. Resistin is secreted mainly from macrophages in humans. It possesses proinflammatory properties. Controversial results about its role on obesity, insulin resistance and metabolic syndrome have been reported. In the first study of this thesis, resistin levels were measured from 1500 Finnish subjects in the cross-sectional Health 2000 study. Higher resistin levels were detected in subjects fulfilling the criteria for metabolic syndrome compared to subjects without metabolic syndrome. Resistin was associated with several components of metabolic syndrome. Data derived from epidemiological studies show that low birth weight is associated with an increased risk for chronic diseases in adulthood. A rat model of intrauterine growth restriction was created. In the second study, unfavorable changes in the peptide hormones resistin and adiponectin were detected that may predispose rats to subsequent insulin resistance. In addition to intrauterine growth restriction, the effect of postnatal fructose-rich diet was explored in the third study. Intrauterine growth restriction and postnatal fructose diet decreased body weight and induced adverse changes in lipid and glucose metabolism in offspring. However, fetally growth-restricted rats were not more susceptible to the adverse effect of fructose diet. In conclusion, this study demonstrates that resistin is associated with metabolic syndrome and is increased by intrauterine growth restriction. Restricted maternal diet during pregnancy influences weight and lipid metabolism in rat offspring. / Tiivistelmä Metaboliseksi oireyhtymäksi kutsutaan sydän- ja verisuonitautien sekä tyypin 2 diabeteksen riskitekijöiden kasaumaa. Näitä riskitekijöitä ovat keskivartalolihavuus, heikentynyt glukoosin sieto, insuliiniresistenssi, korkea verenpaine sekä rasva-aineenvaihdunnan häiriöt, erityisesti korkea triglyseridipitoisuus ja matala HDL-taso. Näiden tekijöiden taustalta ei ole löydetty selkeää yhdistävää mekanismia. Tämän väitöskirjan tavoitteena oli tutkia resistiinin yhteyttä metaboliseen oireyhtymään sekä selvittää, altistaako raskauden aikainen aliravitsemus ja siihen liittyvä alhainen syntymäpaino häiriöille rasva- ja glukoosiaineenvaihdunnassa sekä peptidihormoneissa rotalla. Resistiini erittyy ihmisellä pääasiassa tulehdussoluista, erityisesti makrofageista. Sillä on todettu olevan tulehdusta edistäviä vaikutuksia. Resistiinin yhteydestä lihavuuteen, insuliiniresistenssiin ja metaboliseen oireyhtymään on julkaistu ristiriitaisia tuloksia. Väitöskirjan ensimmäisessä osatyössä plasman resistiinipitoisuudet määritettiin 1500 suomalaiselta poikkitieteellisessä Terveys 2000 -tutkimuksessa. Havaittiin, että resistiinipitoisuudet olivat korkeammat niillä tutkimushenkilöillä, joilla oli metabolinen oireyhtymä verrattuna henkilöihin, joilta oireyhtymä puuttui. Epidemiologisissa tutkimuksissa on havaittu, että alhainen syntymäpaino on yhteydessä korkeampaan riskiin sairastua moniin kroonisiin sairauksiin, kuten sydän- ja verisuonitauteihin aikuisiässä. Toisessa ja kolmannessa osatyössä tutkittiin rottamallissa raskauden aikaisen ravintorajoituksen vaikutusta jälkeläisten kasvuun, rasva- ja sokerimetaboliaan sekä peptidihormoneihin. Toisessa osatyössä todettiin, että rajoitettu ravinto raskauden aikana aiheutti haitallisia muutoksia resistiini- ja adiponektiinipitoisuuksissa altistaen jälkeläiset insuliiniresistenssille. Kolmannessa osatyössä tutkittiin lisäksi syntymänjälkeisen fruktoosipitoisen ravinnon vaikutuksia. Raskauden aikaisen aliravitsemuksen ja fruktoosiravinnon vaikutuksesta rotat olivat aikuisena pienempiä ja niillä havaittiin häiriöitä rasva- ja sokeriaineenvaihdunnassa. Tutkimus osoittaa, että korkea plasman resistiini-pitoisuus liittyy metaboliseen oireyhtymään. Lisäksi voidaan todeta, että rajoitettu ravinto raskauden aikana aiheuttaa rotalla korkeamman resistiini-pitoisuuden lisäksi muutoksia painossa ja rasva-aineenvaihdunnassa.

Abstract Blood pressure is usually measured on a clinic visit as a momentary value. It can also be defined as a continuum based on several repeated measurements. Ambulatory blood pressure measurement (ABPM) is a method of repeated BP measurements targeted to evaluate the circadian blood pressure (BP). Nondipping, i.e., the lack of reduction of BP during the night, has been shown to associate with cardiovascular endpoints. The aim of this study was to investigate the association between 24-hour ABPM and cardio-metabolic confounders in a cross-sectional, population-based study design. Particular attention was paid to the nondipping phenomenon. Adiponectin, a hormone secreted by the adipose tissue, has vasoprotective and anti-inflammatory effects. Reduced adiponectin level has been associated with hypertension. In this study adiponectin level was inversely associated with daytime systolic BP, but showed no association with nondipping. Hypertension is one component of metabolic syndrome (MS). MS has been associated with nondipping. The association between ABPM and metabolic abnormalities was studied in subjects without known hypertension or type 2 diabetes. Subjects with impaired glucose metabolism were more likely to belong to the group of nondippers. Fatty liver is considered as the hepatic manifestation of MS. A significantly higher prevalence of fatty liver has been seen in hypertensives compared to normotensive controls, elevating their risk for cardiovascular morbidity. The association between ABPM characteristics and fatty liver was evaluated in the present study. Significantly higher systolic ABPM levels were seen in subjects with fatty liver, but no association with nondipping existed. The kidney vasculature is prone to injury under a high continuous circadian BP load and lacking nighttime drop. This may lead to diminished glomerular filtration rate. Our study showed a significant independent association between renal function and the dipping status. Reduction in renal function was associated with increased risk of nondipping pattern. Carotid intima-media thickness (cIMT), the surrogate marker of early atherosclerosis, has been associated with blunted nocturnal BP drop. The association between cIMT and dipping status was explored. Nondipping pattern was associated with increased cIMT. In conclusion, ABPM specifies the information of circadian and nighttime BP level not achievable with conventional BP measurement. This is especially beneficial in metabolic abnormalities when the risk of cardiovascular morbidity is increased. / Tiivistelmä Väitöstutkimuksessa osoitettiin, että vuorokausiverenpaineen mittauksella eli ambulatorisella verenpaineenmittauksella on erityistä merkitystä sydän- ja verenpainesairastavuutta lisäävien metabolisten häiriöiden yhteydessä. Työssä haluttiin selvittää 24 tunnin aikana mitatun verenpainetason ja puuttuvan yöaikaisen verenpaineenlaskun eli nondipping-ilmiön yhteyttä tunnettuihin metabolisiin riskitekijöihin ja kaulavaltimoseinämän paksuuntumaan. Kyseessä on suomalaiseen, keski-ikäiseen väestöotokseen kohdistunut poikkileikkaustutkimus. Tavallisesti yöaikainen verenpainetaso laskee 10&#160;% tai enemmän päiväaikaiseen verenpainetasoon nähden (dipping). Verenpaineen lasku voi kuitenkin jäädä puutteelliseksi (nondipping). Nondipping-ilmiön on todettu lisäävän sydän- ja verisuonisairastuvuuden riskiä. Kaulavaltimoseinämän paksuuntumaa on pidetty merkkinä varhaisesta valtimosairaudesta ja maksan rasvakertymä katsottu osaksi metabolista oireyhtymää. Metabolisiin häiriöihin sekä munuaistoiminnan häiriöihin liittyy lisääntynyt valtimosairauden riski. Väitöstutkimuksessa vuorokausiverenpaine mitattiin mukana kannettavalla automaattisella verenpaineenmittausmenetelmällä eli ambulatorisella verenpaineenmittauksella. Lisäksi verenpaine mitattiin tavalliseen tapaan vastaanottokäynnin yhteydessä. Maksan rasvaisuutta ja kaulavaltimon seinämäpaksuutta tutkittiin ultraäänilaitteella. Tavanomaisten taustamuuttujien lisäksi kerättiin laboratoriotietoa sokeriaineenvaihdunnasta, munuaissuodoksen määrästä sekä rasvakudoksen erittämän adiponektiinihormonin määrästä. Nondipping-ilmiön todettiin olevan itsenäisesti yhteydessä sokeriaineenvaihdunnan häiriöön, munuaissuodoksen alenemaan ja kaulavaltimon seinämäpaksuuntumaan. Kohonnut päiväaikainen systolinen verenpainetaso oli yhteydessä verisuoniston kannalta epäedulliseen adiponektiinihormonitasoon. Sekä systolinen että diastolinen verenpainetaso oli korkeampi henkilöillä, joilla todettiin maksan rasvoittuma kuin niillä, joilla ei ollut maksan rasvoittumaa. Tutkimus osoitti ambulatorisen verenpaineenmittauksen tuovan merkittävää lisätietoa etenkin sydän- ja verisuonisairastuvuuden riskiä jo sinällään lisäävissä tiloissa, kuten metabolisissa häiriöissä ja munuaistoiminnan alentumassa. Koska metaboliset häiriöt lisääntyvät jatkuvasti, on todennäköistä, että vuorokausiverenpaineen mittaus yleistyy osana valtimosairastavuuden kokonaisriskin arviointia.

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