Introdução: O diabetes mellitus (DM) é uma condição prevalente, de alto custo e associada a várias complicações. Apesar dos potenciais benefícios do rastreamento para DM em indivíduos de alto risco, o rastreamento ainda é controverso. Em 2001, o Brasil realizou um programa Nacional de rastreamento para DM, convidando todos os indivíduos a partir dos 40 anos de idade a participar. Objetivos: Este estudo tem como objetivos descrever a implementação do programa de rastreamento; estimar sua efetividade e impacto populacional; estimar o custo por caso de DM diagnosticado; e avaliar o custoefetividade da estratégia de rastreamento. Métodos: Foi construído um modelo de decisão analítico. Os parâmetros para a fase de rastreamento foram estimados a partir de dados do Ministério da Saúde e estudo de seguimento de uma amostra de 90,106 participantes do rastreamento. As etapas de diagnóstico e vinculação de casos de DM aos serviços de saúde foram avaliadas em uma sub-amostra de 4,906 indivíduos com rastreamento positivo. Custos do programa e custos do DM foram estimados (em R$, US$ e Int$ para o ano de 2001). Para a análise de custo-efetividade, o modelo de decisão analítico foi incorporado a um modelo de Markov de progressão do DM.Foram estimados os custos e benefícios (em anos de vida salvos e anos de vida ajustados para qualidade - AVAQ) durante toda a vida para cada caso de DM. Fontes adicionais de dados incluíram dados de inquéritos nacionais, DATASUS, Instituto Brasileiro de Geografia e Estatística (IBGE) e literatura. O horizonte de análise foi da vida toda e assumiu a perspectiva do Sistema Único de Saúde (SUS). Não foram considerados custos de perda de produtividade. Taxa de desconto de 5% foi aplicada aos custos e benefícios futuros. Foi calculada a razão de custoefetividade adicional do rastreamento populacional, comparado à ausência de programa de rastreamento. Resultados: Dos 22.069.095 de testes de rastreamento realizados, 3.417.106 resultaram positivos. Foi estimado que aproximadamente 346 mil novos casos de DM foram diagnosticados e 320 mil novos casos foram incorporados ao SUS. Foi necessário rastrear 64 indivíduos para diagnosticar 1 caso de DM. O custo total federal do programa de rastreamento foi de R$39 milhões (US$16,5 milhões; Int$50 milhões). O custo porcada caso de DM diagnosticado foi de R$136 (US$58; Int$175). A razão de custo-efetividade do programa de rastreamento foi estimada em R$ 15.216 (US$ 6.475; Int$ 19.608) por ano de vida salvo ou R$ 14.164 (US$ 6.027; Int$ 18.252) por AVAQ. Conclusões: O programa de rastreamento realizado no Brasil foi uma iniciativa inédita, efetivo na mobilização de municípios e da população. Apesar dos altos custos, o custo por caso de DM diagnosticado foi inferior ao relatado por outros países. A razão de custo-efetividade foi semelhante à estimada por simulações do rastreamento seletivo em indivíduos de alto risco. Considerando evidências recentes de efetividade do tratamento precoce na redução de complicações e mortalidade por DM, análises de sensibilidade deverão ser realizadas considerando a variação destes parâmetros. Estes resultados são importantes para tomadores de decisão, em especial em países considerando estratégias de rastreamento para DM. / Introduction: Diabetes mellitus (DM) is a common and costly disorder associated with major complications. Despite the rationale for screening high-risk individuals, direct evidence on the effectiveness of diabetes population screening has not been demonstrated. In 2001 Brazilian citizens aged 40 or older were invited to participate in a nationwide population screening program for DM. Objectives: The objectives of this study are to evaluate the initial impact of the program, estimate the cost per DM case diagnosed, and conduct a cost-effectiveness analysis of the Brazilian nationwide screening program considering lifetime disease progression. Methods: A decision analytic model with a screening phase and a diagnostic phase was developed. Model parameters considered data from National screening program and from a follow-up study of 90,106 screenees. To describe the actions taken for positive screenees, a sub-sample of 4,906 positive screenees was actively followed up through home interviews. Program cost data (in R$, US$ and Int$ considering 2001 exchange rates) and disease costs were estimated. For the cost-effectiveness analysis, the decision analytic model was incorporated into a Markov model of DM disease progression. Lifetime costs and benefits for individuals newly diagnosed with DM were estimated. Additional sources of data included national registries, surveys, and data from the literature. The analysis considered the health care system perspective and lifetime horizon. Productivity losses were not considered. Discount rate of 5% was considered in the base-case analysis.The incremental cost-effectiveness ratio was estimated comparing screening program with no screening program. Results: Of a total of 22,069,905 tests performed, an estimated 3,417,106 were positive. Approximately 345,000 new DM cases were diagnosed, and 320,000 were incorporated into the healthcare system. The number of screening tests needed to detect one case of DM was 64. Total screening program costs were R$ 39 million (US$ 16.5 million or Int$ 50 million). The cost per new DM case diagnosed was R$ 136 (US$ 58 or Int$ 175). Results were sensitive to proportion of individuals returning for diagnostic confirmation. Compared with no screening, the incremental cost for population screening was estimated as R$ 15,261 (US$ 6,475; Int$ 19,608) per life-year saved, and R$ 14,164 (US$ 6,027; Int$ 18,252) per QALY. Conclusions: This pioneering nationwide population-based screening conducted through primary healthcare services was effective in mobilizing municipalities andpopulation. Despite significant overall costs, cost per new DM case diagnosed was lower than described by other countries. Cost-effectiveness ratios of the Brazilian Nationwide population screening program incorporating long-term disease management are similar to those estimated for selective screening of high risk population based on modeling studies. Considering recent evidence on effectiveness of DM treatment in reducing complications and mortality, sensitivity analysis should be conducted considering different parameter estimates. These data provides invaluable information for decision makers, especially to other countries planning screening programs for early diagnosis of DM.

Orientador: Licio Augusto Velloso / Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T08:42:14Z (GMT). No. of bitstreams: 1 Albuquerque_GabrielaGiraode_D.pdf: 1649056 bytes, checksum: 5f50462f0ce9c30dfa336c07fbd9d35b (MD5) Previous issue date: 2010 / Resumo: A prevalência global de diabetes mellitus do tipo 2 vem aumentando rapidamente em paralelo ao aumento do número de casos de obesidade. Entretanto, os métodos terapêuticos empregados para esta doença permanecem insatisfatórios. Existem drogas potencializadoras das ações da insulina e fármacos que estimulam a secreção de insulina, no entanto nenhum medicamento atualmente disponível é capaz de corrigir simultaneamente todas as disfunções envolvidas na gênese do diabetes mellitus tipo 2, além disso, a maior parte destes, perde a eficácia depois de alguns anos de evolução da doença. Dessa forma os desafios para as novas drogas sensibilizadoras e estimuladoras da secreção de insulina será oferecer uma eficácia equivalente às drogas disponíveis, com menor número de efeitos colaterais e ação mais estável. Estudos recentes têm revelado que o coativador de transcrição gênica PGC-1alfa está associado com a regulação da gliconeogênese hepática e secreção de insulina. Sendo a proteína PGC- 1alfa uma importante co-ativadora de fatores de transcrição, e visto que sua inibição parcial provoca uma melhora geral no quadro de DM2, decidimos investigar os efeitos da inibição de PGC-1alfa em modelos animais de obesidade e DM2. Os resultados mostraram que a inibição de PGC-1alfa, através de um oligonucleotídeo antisense (PGC-1aAS), em animais obesos e diabéticos provoca aumento na secreção de insulina em cultura e in vivo e reduz os níveis glicêmicos sem provocar hipoglicemia. Além disso, há aumento no consumo de glicose, medido por clamp euglicêmicohiperinsulinêmico e redução da produção hepática de glicose. Ainda, a inibição da PGC-1alfa causou reversão da esteatose hepática induzida por dieta e pelo uso de etanol. Isso foi acompanhado pelo aumento da fosforilação e ativação da enzima Akt e pela fosforilação/inativação do fator de transcrição FOXO1 promovendo melhora da ação molecular da insulina no fígado. Assim, concluímos que a inibição da expressão de PGC-1alfa pode ser um método terapêutico de interesse para o tratamento de diabetes mellitus do tipo 2 e condições metabólicas afins. / Abstract: Type 2 diabetes mellitus is one of the most prevalent and threatening diseases in modern societies. Nevertheless, the therapeutic approaches currently used are insufficient to promote adequate metabolic control of the disease. There are a number of drugs that increase insulin secretion and also drugs that enhance insulin action. However, no compound currently available is capable of simultaneously correcting insulin secretion and action defects present in diabetes. Recent data has provided evidence for the role of the co-activator of gene transcription, PGC-1alfa, on the control of insulin secretion and hepatic glucose production. Therefore, we have decided to evaluate the effects of an antisense oligonucleotide compound designed to inhibit PGC-1alfa expression, on the control of diabetes mellitus in distinct animal models. Our results show that the inhibition of PGC-1alfa increases insulin secretion in diabetic and obese animals without leading to hypoglycemia. In addition, the compound increased glucose action in peripheral tissues, improved glucose clearance during an euglycemic-hyperinsulinemic clamp and reduced hepatic glucose production. Finally, the inhibition of PGC-1alfa expression improved hepatic steatosis induced by ethanol and high-fat diet, which was accompanied by increased insulin signal transduction through the Akt/FOXO1 signaling pathway. We conclude that the inhibition of PGC-1alfa may be a potentially useful alternative for the treatment of type 2 diabetes mellitus and associated metabolic dysfunctions. / Doutorado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Doutor em Fisiopatologia Medica

O diabetes mellitus tipo 2 (DM2) constitui um dos mais importantes problemas de saúde pública no mundo. A alta concentração plasmática de triglicérides e a baixa concentração do HDL-C são as principais alterações lipídicas no DM2. A hipertrigliceridemia, além de outros fatores, pode alterar a composição das lipoproteínas, ocasionando alterações funcionais das partículas. O efeito antiaterogênico da HDL se dá, sobretudo, devido à sua ação de promover o Transporte Reverso do Colesterol, sendo a troca lipídica entre as lipoproteínas uma das etapas desse processo. O objetivo deste trabalho foi avaliar o tamanho da partícula de HDL e sua capacidade em receber seus lípides constituintes de outras lipoproteínas. O método é baseado na troca lipídica ocorrida entre uma nanoemulsão artificial (LDE) marcada radioativamente com 14C-CL e 3H-TG ou 14CFL e 3H-CE que se assemelha à estrutura lipídica da LDL, usada como doador de lipídeos. Neste trabalho foram estudados 45 pacientes diabéticos (53±7 anos) e 45 indivíduos sem a doença (55±8 anos), como grupo controle. As taxas de transferência de colesterol livre e fosfolípides para a HDL foram maiores no grupo dos pacientes diabéticos quando comparados com o grupo controle (CL= 7,1±1,7 e 6,4±1,4%, p=0,0400; FL= 23,6±2,4 e 19,3±3,3%, p<0,0001, respectivamente). No entanto, não houve diferença na transferência de éster de colesterol e triglicérides entre os pacientes diabéticos e indivíduos controles. O tamanho da partícula de HDL também não foi diferente entre os grupos. As transferências de éster de colesterol, triglicérides e colesterol livre correlacionaram-se positivamente. Houve também correlação positiva entre a concentração plasmática do colesterol total e LDL-C com a taxa de transferência de triglicérides e entre a concentração plasmática da apoAI com a taxa de transferência de éster de colesterol e de colesterol livre. Em virtude da partícula de HDL ter importante papel antiaterogênico, a maior transferência de FL e CL para a HDL no DM2, podem ser relevantes para estabelecer mecanismos antiaterogêncios associados a alterações na lipoproteína relacionados com o DM2. / Type II diabetes mellitus has become one of the world\'s main public health issues. High triglyceride concentrations and low HDL-C concentrations are the main in the plasma lipids found in DM2. Hipertriglyceridemia is but one of the factors that cause lipoprotein composition, which in turn can cause alterations in particle function. The antiatherogenic effect of HDL is due primarily to its ability to promote Reverse Cholesterol Transport, in which lipid transfer between lipoproteins is one step in the process. The objective of this study was to evaluate HDL particle size and its capacity to accept lipid constituents from other lipoproteins. The methodology utilized is based on the lipid transfer between with an artificial cholesterol-rich nanoemulsion labeled with 3H-tryglicerides (TG) and 14C-free cholesterol (FC) or 3H-cholesteryl ester (CE) and 14C-phospholipids (PL), structurally similar to LDL, used as a radioactive lipid donator. After LDE and other lipoprotein precipitation, the capacity of HDL to receive lipids is quantified by measuring the radioactivity present in the lipoprotein. Forty-five diabetic individuals (53±7) and 45 non-diabetic individual (55±8) as a control group were studied. The free cholesterol (FC) and phospholipids (PL) transfer rate to HDL was higher for the diabetic group when compared with control group (FC= 7.1±1.7 e 6.4±1.4%, p=0.0400; PL= 23.6±2.4 e 19.3±3.3%, p<0.0001, respectively). However, there was no transfer difference of the cholesteryl ester and triglycerides between the two study groups. No difference in the HDL particle size was observed in either group. There was found correlations between the lipid transfer rates and between the transfer rates and the lipoprotein profile of the diabetic individuals were also analyzed. The transfer of cholesteryl ester, triglycerides and free cholesterol correlated positively. There was also a positive correlation between the plasmatic concentration of total cholesterol and LDL-C with the triglyceride transfer and between the plasmatic concentration of apoAI with the cholesteryl ester and free cholesterol. This pattern of greater PL and FC transfer to HDL associated with DM2 can be a marker related to functional alterations in HDL that may contribute to atherogenic in those patients.

Foi desenvolvido um estudo observacional de corte transversal, com o objetivo de avaliar o status em Mg de pacientes com diabetes mellitus tipo 2. A amostra foi composta por 51 indivíduos de ambos os gêneros, com idade média de 53,6 ± 10,5 anos, os quais foram selecionados no Ambulatório de Endocrinologia do Hospital Universitário Onofre Lopes (HUOL) Natal/RN. O projeto foi aprovado pelos Comitês de Ética em Pesquisa do HUOL e da Faculdade de Ciências Farmacêuticas da USP. Os pacientes foram submetidos à avaliação antropométrica, dietética, do controle glicêmico, função renal, perfil lipídico, Mg plasmático, eritrocitário, urinário e dietético. Foi observada ingestão adequada de macronutrientes, contudo baixo consumo dietético de Mg e de fibras. Identificou-se, ainda, controle glicêmico e perfil lipídico insatisfatórios e função renal sem alterações significativas. Quanto ao status de Mg, 70,6 % da amostra apresentaram algum dos parâmetros bioquímicos relativos a este mineral abaixo dos valores de referência, sendo estes menores nos indivíduos que tinham mais complicações metabólicas e presença de microalbuminúria. Foram observadas correlações inversas entre o Mg plasmático com a glicemia de jejum (r = -0,281, p = 0,046) e a pós-prandial (r = -0,322, p = 0,021), e correlações positivas entre o Mg urinário com a glicemia de jejum (r = 0,291, p = 0,038), a circunferência abdominal (r = 0,288, p = 0,041) e o IMC (r = 0,282, p = 0,045). Deste modo, foram diagnosticadas alterações no status de Mg, as quais foram mais evidentes nos pacientes que tinham mais complicações, demonstrando a associação dos fatores relacionados com essa doença e o Mg. / A cross-sectional study was carried out to evaluate Mg status in patients with type 2 diabetes mellitus. The sample comprehended 51 individuals, both male and female, aged 53.6 ± 10.5 years, selected from the Endocrinology Clinic of the University Hospital Onofre Lopes (HUOL) in Natal/RN, Brazil. The project was approved by the Commission on Ethics in Research of the HUOL and Faculty of Pharmaceutical Sciences of the University of São Paulo. The patients were assessed concerning anthropometry, diet, blood-glucose control, kidney functioning and lipid profile, besides plasma, erythrocyte, urinary and dietary Mg. An adequate intake of macronutrients and a low consumption of dietary Mg and fibers were observed. Unsatisfactory blood-glucose control and lipid profiles, besides kidney functioning without significant alterations, were also observed. Concerning Mg status, 70.6% of the sample presented biochemical parameters for this mineral below the reference values, and such parameters were lower in individuals with more extensive metabolic complications and microalbuminury. Inverse correlations between plasma Mg with fasting (r = -0.281, p = 0.046) and postprandial plasma glucose (r = -0.322, p = 0.021), and a positive correlation between urinary Mg with fasting plasma glucose (r = 0.291, p = 0.038), waist circumference (r = 0.288, p = 0.041) and body weight index (r = 0.282, p = 0.045) were observed. Therefore, alterations in Mg status were detected in the studied population. Such alterations were more evident in patients with more extensive complications, thus demonstrating the association of factors related to this disease and Mg.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2018-05-25T11:52:26Z No. of bitstreams: 1 caiomendesdefreitas.pdf: 4475109 bytes, checksum: b27bb514b29c024ad61c1114d0539e66 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-06-14T11:52:39Z (GMT) No. of bitstreams: 1 caiomendesdefreitas.pdf: 4475109 bytes, checksum: b27bb514b29c024ad61c1114d0539e66 (MD5) / Made available in DSpace on 2018-06-14T11:52:39Z (GMT). No. of bitstreams: 1 caiomendesdefreitas.pdf: 4475109 bytes, checksum: b27bb514b29c024ad61c1114d0539e66 (MD5) Previous issue date: 2018-02-28 / A presente pesquisa insere-se na perspectiva da psiconeuroimunologia e tem por objetivo investigar a sintomatologia depressiva, sua possível associação ao estresse psicológico e a marcadores endócrinos e imunológicos em pacientes portadores de Diabetes Mellitus Tipo 2 (DM2) acompanhados em um centro especializado de condições crônicas em Juiz de Fora (MG). Participaram do estudo 92 pacientes com DM2, divididos nos seguintes grupos: sem depressão (n=58), depressão leve (n=12), depressão moderada (n=8) e depressão grave (n=13). Foram utilizados o Inventário de Depressão de Beck (BDI-II) como medida de depressão, a Escala de Estresse Percebido (PPS-10) para medir o estresse, a escala SF-6D para avaliação do estado de saúde, sobre religiosidade/espiritualidade (R/E) a Medida Multidimensional Breve de Religiosidade/Espiritualidade (BMMRS-P) e outra sobre a felicidade subjetiva (Brazilian Version of The Sujective Happiness Scale). Foram investigadas as diferenças entre os grupos quanto ao estresse, R/E, felicidade, estado de saúde, variáveis bioquímicas (HbA1c e o nível da glicemia em jejum) e imunológicas (leucócitos, neutrófilos, linfócitos, monócitos). O tratamento estatístico foi realizado utilizando-se o teste qui-quadrado (x²) de Pearson para as variáveis categóricas e a análise de variância (ANOVA) e o teste de kruskal-wallis para as variáveis numéricas, seguidos de pos hoc tests (Bonferroni e Mann-Whitney, respectivamente). Obteve-se relações significativas (x²) entre o sexo (feminino) e depressão grave (p=0,021), assim como entre a dimensão fé religiosa/espiritual e gravidade do nível de depressão (p=0,001). Observou-se também uma associação significativa entre estresse percebido e depressão (p=0.000; F=35,212), assim como com estado de saúde (p=0.000; F=20,333) e o suporte religioso (p=0.013; F=3,823), bem como associações significativas entre experiências espirituais religiosas e níveis de depressão (p=0,001; H=17,352), superação religiosa/espiritual (p=0,049; H=7,847), auto-avaliação global religiosa/espiritual (p=0,001; H=13,431), e felicidade subjetiva (p=0,000; H=20,514). Os resultados do estudo podem auxiliar na elaboração de estratégias de promoção, prevenção e intervenção com foco na saúde mental de pacientes com DM, tais como psicoterapia, técnicas de relaxamento (meditação e yoga), assim como educação em diabetes, criando condições propícias para a evolução favorável da doença, tendo como conseqüência a melhoria geral na qualidade de vida destas pessoas. / The aim of the study was to investigate the depressive symptomatology associated to psychological stress in patients with Type 2 Diabetes Mellitus (DM2) in a specialized center of chronic conditions of Juiz de Fora – MG, in a psychoneuroimmunology framework. 92 patients with DM2, divided into four groups, took part in the study: no depression (n=58), mild depression (n=12), moderate depression (n=8) and severe depression (13). Depression [(Beck Depression Inventory (BDI-II)], stress (Perceived Stress scale (PPS-10)], health condition (SF-6D), religiousness/spirituality (R/E) (Brief Multidimensional Measurement of religiousness/Spirituality - BMMRS-P) and the subjective happiness (Brazilian Version of The Sujective Happiness Scale) were measured. The Pearson Qui-square test was used for categorical variables; analysis of variance (ANOVA) and kruskal-wallis test were used for numeric variables all at a significant p < 0.05, as well as pos hoc tests (Bonferroni and Mann-Whitny, respectively). A significant relationship (x²) between feminine gender and severe depression (p=0,021) was found, as well faith and levels of depression (p=0,001). Was also observed a significant relationship between perceived psychological stress and levels of depression (p=0.000; F=35,212), as well as health status (p=0.00; F=20,333) and religious support (p=0.013; F=3,823). In the Kruskal-Wallis test, there was a significant relationship between religious spiritual experiences and levels of depression (p=0,001; H=17,352), as well overcoming (religious / spiritual) (p=0,049; H=17,352), global self-assessment (religious / spiritual) (p=0,001; H=13,431) and subjective happiness (p=0.000; H=20,514). It is intended to use the data to elaborate strategies to promote and prevent, as well as to develop mental health interventions with diabetic patients and/or patients with other metabolic diseases aiming to create conditions for the favourable evolution of the disease, and a general improvement in the quality of life of these patients. Psychotherapy, relaxation techniques (such as meditation and yoga) as well as diabetes education may be relevant tools for more favorable prognoses in the evolution of the condition in question.

Estudo descritivo transversal, cujo objetivo foi analisar a relação das variáveis sociodemográficas, de tratamento, hábitos de vida, clínicas e laboratoriais com as variáveis sintomas e fases do estresse, em pessoas com diabetes mellitus tipo 2, em unidade ambulatorial de hospital de nível terciário de atenção à saúde. A amostra foi constituída por 222 pessoas e os dados foram coletados no período de junho de 2011 a agosto de 2012. O instrumento utilizado foi o Inventário de Sintomas de Stress de Lipp, composto por três quadros de sintomas de estresse, que fornecem porcentagens para classifica-los em quatro fases: alerta, resistência, quase exaustão e exaustão. Entre as características sociodemográficas, de tratamento, hábitos de vida, dados clínicos e laboratoriais, destacam-se que 53,15% das pessoas eram do sexo feminino, 43,85% do masculino, com média de idade de 60,68 anos (DP=8,40), tempo médio de escolaridade de 5,07 anos (DP=4,15), 71,17% viviam com o companheiro, 57,66% procediam da região de Ribeirão Preto (SP), 50,9% eram aposentados/pensionistas, 87,38% referiu fazer uso de insulina, 78,82% antidiabético oral, 68,91% seguir a dieta recomendada e 46,85% não praticava exercícios físicos regulares. O tempo médio de diagnóstico foi de 15,15 (DP=8,03) anos, índice de massa corporal 32,10 (DP=5,75) Kg/m2 , pressão arterial sistólica 180,10 (DP=14,03) mmHg e diastólica 143,7 (DP=23,63) mmHg, taxa de hemoglobina glicada 9,446 (DP=2) %, colesterol total 74,9 (DP=41,95) mg/dl, lipoproteína de alta densidade 35,67 (DP=8,58) mg/dl, lipoproteína de baixa densidade 101,55 (34,52) mg/dl e triglicerídeos 203,60 (DP=147,72) mg/dl. Quanto às variáveis do estresse, destaca-se que a maior média das porcentagens obtidas ocorreu para os sintomas de estresse do quadro 2 (20,16%-DP=20,165). Para fins de análises estatísticas, excluiu-se a fase de alerta e aglutinou-se as de exaustão e quase exaustão. A frequência dos sintomas de estresse referidos pelos participantes nos três quadros distintos permitiu verificar a presença do estresse em 63,51% da amostra, bem como a frequência de 53,60% na fase de resistência ao estresse, e predomínio de sintomas físicos (61,53%). As fases do estresse associaram-se com a idade, procedência, uso de insulina e lipoproteína de baixa densidade; os sintomas do estresse com o uso de antidiabéticos orais, tabagismo, consumo de bebida alcoólica e lipoproteína de baixa densidade. Quanto à porcentagem média obtida nos três quadros, observou-se que houve associação dos sintomas do primeiro quadro com a ocupação; do segundo quadro com o seguimento da dieta, glicemia plasmática de jejum, o colesterol total e lipoproteína de baixa densidade; correlação do terceiro quadro com o índice de massa corporal, de modo positivo e com a renda familiar, de modo negativo. A idade e a hemoglobina glicada correlacionaram-se com o segundo e terceiro quadros, porém de forma negativa e positiva, respectivamente. O presente estudo permitiu conhecer as possíveis relações do estresse com as variáveis sociodemográficas, tratamento da doença, hábitos de vida, clínicas e laboratoriais da pessoa com diabetes mellitus tipo 2 e reitera a importância desse conhecimento na prática clínica para intervenções que desenvolvam habilidades pessoais para o enfrentamento de situações estressantes percebidas pelas pessoas durante o curso da doença / Cross-sectional study aimed to examine the relations of sociodemographic variables, disease treatment, lifestyle, clinical and laboratory variables with the symptoms and phases of stress in people with type 2 diabetes mellitus, in an outpatient unit of a tertiary level hospital of health care. The sample consisted of 222 individuals and the data were collected between June 2011 and August 2012. The instrument used was the Lipp Stress Symptom Inventory, composed of three frames of stress symptoms, which provide percentages for grades them into four phases: alarm, resistance, near exhaustion and exhaustion. Among the sociodemographic characteristics, treatment, lifestyle, clinical and laboratory data, it highlights that 53.15% of those were female, 43.85% male, with a mean age of 60.68 years (SD = 8.40), mean years of education 5.07 years (SD = 4.15), 71.17% lived with a partner, 57.66% were from Ribeirao Preto region (SP) and 50.9% were retired / pensioners, 87.38% reported use insulin, 78.82% oral antidiabetic, 68.91% followed the recommended diet and 46.85% did not practice regular physical exercise. The average time of diagnosis was 15.15 (SD = 8.03) years, mean body mass index 32.10 (SD = 5.75) kg/m2, mean systolic blood pressure 180.10 (SD = 14 03) and diastolic 143.7 mmHg (SD = 23.63) mmHg, glycated hemoglobin rate 9.446 (SD = 2)%, total cholesterol 74.9 (SD = 41.95) mg/dl, high density lipoproteins 35.67 (SD = 8.58) mg/dL, low density lipoproteins 101.55 (34.52) mg/dL and triglycerides rate of 203.60 (SD = 147.72) mg/dl. As for the variables of stress, there is that most average of these percentages occurred to the frame stress symptoms 2 (20.16% - SD = 20.165). For the purpose of statistical analysis, we excluded the alert phase and connect them of exhaustion and near exhaustion. The frequency of symptoms of stress reported by participants in three different frames demonstrated the presence of stress in 63.51% of the sample, and the frequency of 53.60% in stress resistance phase, and predominance of physical symptoms (61,53%). The phases of stress were associated with age, origin, use of insulin and low-density lipoprotein; symptoms of stress with the use of oral antidiabetic drugs, smoking, consumption of alcohol and low-density lipoprotein. The average percentage obtained in the three frames, it was noted that there was an association of the symptoms of the first frame with the occupation; the second frame with the following the diet, fasting plasma glucose, total cholesterol and low-density lipoprotein; the third frame correlation with body mass index in a positive way and to family income, negatively. The age and glycated hemoglobin correlated with the second and third frames, but negatively and positively, respectively. This study helped identify the possible relations of stress with sociodemographic variables, disease treatment, lifestyle, clinical and laboratory of the person with type 2 diabetes mellitus and reiterates the importance of this knowledge in clinical practice to interventions that develop personal skills for coping stressful situations perceived by the people during the course of the disease

L’amélioration de la surveillance de la sécurité des médicaments grâce à l’utilisation des bases de données médico-administratives est source de nombreuses promesses. L’objectif de cette thèse était de développer un système automatisé de détection et de priorisation des signaux de sécurité adapté aux bases de données médico-administratives, pour la surveillance de la sécurité des médicaments des maladies chroniques. Les antidiabétiques non insuliniques (ANI) ont été sélectionnés comme cas d’étude pour le développement et l’évaluation de ce système. Nous avons d’abord étudié le profil d’utilisation des ANI en France, et avons retrouvé un fort mésusage des inhibiteurs de la dipeptidylpeptidase-4 (DPP-4) ainsi qu’un risque accru de non observance avec ces derniers. Nous avons ensuite réalisé deux revues de la littérature qui nous ont permis de sélectionner, pour la détection, la méthode sequence symmetry analysis, et de construire, pour la priorisation, notre algorithme que nous avons structuré autour de la force, la nouveauté, l’impact du signal de sécurité, et les modalités d’utilisation du médicament. Nous avons enfin évalué, d’une part, les performances du système développé, dans une étude pilote sur les ANI qui a montré des résultats satisfaisants et permis d’identifier un nouveau signal de sécurité entre les inhibiteurs de la DPP-4 et les événements thromboemboliques veineux, et d’autre part, son acceptabilité auprès des décideurs de santé qui l’ont jugé positivement. Ces résultats nous invitent à poursuivre nos recherches sur l’amélioration et la validation du système développé. / The improvement of the surveillance of the drug safety by using healthcare databases is waited with hope for a decade. The objective of this thesis was to develop an automated system combining detection and prioritization of safety signals from healthcare databases, for the surveillance of drugs used in chronic diseases. Noninsulin glucose-lowering drugs (NIGLDs) were selected as a case study for the development and the assessment of the system. Firstly, we studied the patterns of use of the NIGLDs in France, and we found a large misuse with the dipeptidylpeptidase-4 (DPP-4) inhibitors and a higher risk of non-observance with their use. Secondly, we conducted two literature review, which allows us to select the sequence symmetry analysis for the detection and to develop our algorithm for the prioritization that we based on strength, novelty, impact of the safety signal, and patterns of drug use. Thirdly, we assessed the performance of the system, in a pilot study on NIGLDs that showed satisfying results and identified a new safety signal with the use of DPP-4 inhibitors and venous thromboembolic events, as well as its acceptability among stakeholders that judged it positively. These results invite us to pursue our researches to improve and to validate the developed system.

Abstract Resistin was discovered in the year 2000. In the mouse, it was reported to be produced by adipocytes and to be linked with insulin resistance and obesity. Human resistin has been shown to be produced by leucocytes but the literature contains contradictory results on its association with obesity and type 2 diabetes. Aim of this study was to clarify the role of resistin in the human context especially in type 2 diabetes and atherosclerosis. The first study examined the possible association of human resistin gene variants with type 2 diabetes. The studied three variants were not associated with type 2 diabetes though they were demonstrated in the second study to be associated with the plasma resistin concentration. However, two gene variants were associated with the prevalence of cerebrovascular disease in subjects with type 2 diabetes. In the third work, the association of the plasma resistin level with the risk factors of atherosclerosis and early atherosclerosis measured with carotid artery intima-media thickness (IMT) were studied. Plasma resistin level was not associated with IMT independently from the known risk factors of atherosclerosis. However, resistin was associated with inflammatory markers highly sensitive CRP and the number of leucocytes whereas insulin resistance did not associate with resistin. In the fourth study, resistin expression in different leucocytes and its modulation, as well as the effect of resistin on monocyte adhesion to endothelium were evaluated. The novel discovery was that resistin is expressed in all the main leucocyte lineages, with monocytes and neutrophils exhibiting the highest relative mRNA and protein levels of resistin. Resistin expression was up-regulated by pro-inflammatory factors in the cells of both innate and adaptive immunity. The present results demonstrating that resistin increases adhesion and expression of some adhesion molecules support the hypothesis that resistin may be involved in the development of atherosclerosis. The above results indicate that resistin is widely produced by leucocytes and therefore may participate in inflammatory processes. Since it may be considered as an inflammatory cytokine, resistin may also influence the development of atherosclerosis. In the future, resistin could possibly be used as a marker of inflammation. / Tiivistelmä Vereen erittyvä uusi hormoni, resistiini, löydettiin vuonna 2000. Hiirellä resistiinin on havaittu erittyvän rasvasoluista ja sen on arveltu toimivan linkkinä lihavuuden ja insuliiniresistenssin välillä. Ihmisellä resistiinin tehtävä on toistaiseksi huomattavasti epäselvempi ja toisin kuin hiirellä ihmisen resistiinin korkein ilmentymistaso on valkosoluissa. Tämän väitöstutkimuksen tarkoituksena oli selvittää ihmisen resistiinin toimintaa ja erityisesti sen liittymäkohtia tyypin 2 diabetekseen ja ateroskleroosiin. Ensimmäisessä osatyössä on selvitetty resistiini-geenin nukleotidimuuntelun yhteyttä tyypin 2 diabetekseen ja siihen liittyviin tekijöihin diabetespotilasaineistossa. Resistiinin geenimuuntelu ei tulosten perusteella ole yhteydessä tyypin 2 diabetekseen, vaikka sillä näyttääkin olevan vaikutusta plasman resistiini-pitoisuuteen, mikä havaittiin toisessa osatyössä. Geenimuuntelulla oli havaittavissa yhteyttä aivovaltimosairauteen. Kolmannessa osatyössä plasman resistiinipitoisuuden yhteyttä valtimonkovettumatautiin ja sen riskitekijöihin tutkittiin Pohjois-Pohjanmaalta kerätyssä aineistossa (n = 525). Plasman resistiinipitoisuudella ei havaittu itsenäistä yhteyttä kaulavaltimonseinämänpaksuuteen, joka kuvastaa alkuvaiheen valtimokovettumataudin tasoa. Tulehdukselliset merkit kuten veren valkosolujen määrä ja plasman CRP-pitoisuus liittyivät suurentuneeseen plasman resistiinipitoisuuteen mutta insuliiniresistenssimuuttujat eivät. Neljännessä osatyössä tutkittiin resistiinin ilmentymistä. Resistiinin havaittiin ilmentyvän kaikissa keskeisissä valkosolutyypeissä ja lisäksi tulehdustekijät lisäsivät sen tuottoa. Erityisesti neutrofiileissä ja monosyyteissä resistiinin ilmentymistasot olivat korkeita. Endoteelisoluilla selvitettiin resistiinin vaikutuksia ateroskleroosiin liittyviin muutoksiin. Resistiini lisäsi monosyyttien kiinnittymistä endoteelisoluihin, mikä on tyypillinen ilmiö varhaiselle ateroskleroosille. Tämän työn tulosten perusteella ihmisen resistiinillä ei ole merkittävää yhteyttä insuliiniresistenssiin ja tyypin 2 diabetekseen. Sen sijaan havainto resistiinin ilmentymisestä useammissa valkosolutyypeissä, kuin mitä aikaisemmin on raportoitu, ja yhteys tulehdustekijöihin osoittaa, että ihmisen resistiinin toiminta liittyy tulehdustiloihin. Resistiini aiheuttaa myös endoteelisoluissa samanlaisia ateroskleroosille altistavia muutoksia kuin muutkin tulehdustekijät. Tulevaisuudessa plasman resistiini-pitoisuutta voidaan mahdollisesti käyttää tulehdustilojen arvioinnissa.

No description available.

Background: Diabetes is a chronic disease affecting more and more people and placing increasing demands on health care. The increasing numbers of adults diagnosed with type 2 diabetes are in need of self-management strategies. Learning self-management includes mastering the skills required to complete the complex emotional and physical tasks necessary to manage well-being and to prevent future complications. A technological service developed with the participation of stakeholders may be an alternative way to meet rising needs for self-management. The involvement of various stakeholders enables cooperation, facilitates patient empowerment, and takes into consideration how adults with type 2 diabetes manage their everyday activities. Aim: The overall aim of the licentiate thesis is, by participatory research methods identify self-management support of a future ICT service to facilitate adults with type 2-diabetes. Methods: Two studies were conducted using participatory design (PD) with qualitative methods. Data were collected among recently diagnosed adults and those with longer experience of type 2 diabetes. The adults were recruited from a primary healthcare centre and from a diabetes hospital clinic in Sweden. Study I identified perceived challenges related to self-management among recently diagnosed adults and those with longer experience of type 2 diabetes by using multistage focus groups. Study II reported needs and wishes for an ICT self-management service to facilitate their everyday life and to deal with type 2 diabetes by using a future workshop. Results: Three main challenges were identified; understanding; developing skills and abilities; and mobilizing personal strengths. Both recently diagnosed adults and those with longer experience of diabetes described challenges in understanding the causes of fluctuating blood glucose and in developing and mobilizing skills for choosing healthful food and eating regularly. The recently diagnosed group were more challenged by learning to accept the diagnosis and becoming motivated to change habit while the experienced group were mainly challenged by issues about complications and medications. The adults with type 2 diabetes expressed needs and wishes for an ICT service all fell under the broad category of Acceptance of the diagnosis, with the three suggestions; Trust in partnerships, Communication and Individualized information. Acceptance of the diagnosis was a prerequisite for managing diabetes successfully. Acceptance of the diagnosis also made the participants accept information, learn about their condition, and understand how to personally manage their everyday lives. Trust in partnership with caregivers and Communication facilitated that acceptance and understanding of the disease. Main findings: The adults with type 2 diabetes stated different needs for support during different phases of the disease. The expressed needs and wishes for an ICT service all fell under the broad category of Acceptance of the diagnosis, with three other suggestions; Trust in partnerships, Communication, and Individualized information. The participants’ experience of the participatory methodology as a democratic process and their appreciation of mutual learning contributed to these results, which are consistent with the aims of person centred care. Conclusions: Adults with diabetes have different needs for support during different phases of the disease. From a person-centred perspective it would be desirable to meet individual needs for self-management on peoples’ own terms through a technological service that could reach and connect to a large number of people. Healthcare practitioners need to address the knowledge needs of patients with type 2 diabetes and support them in developing self-management skills. Consistent with person-centred care, practitioners should also encourage patients’ abilities to mobilize their own personal strengths to maintain self-management. / <p><strong>Forskningsfinansiärer:</strong></p><p>Kommunerna i Skåne Nordost</p><p>Högskolan Kristianstad</p>