La ansiedad rasgo y los recursos de afrontamiento han demostrado tener repercusiones significativas en la vivencia de la diabetes tipo II, es por ello que el presente estudio tiene como objetivo conocer la relación entre ambas variables psicológicas en un grupo de pacientes con el diagnóstico de diabetes tipo II. La muestra se encuentra conformada por 65 participantes entre 40 y 80 años provenientes de un hospital de Lima Metropolitana a quienes se les aplicó la Escala de Ansiedad Rasgo del Inventario de Ansiedad Rasgo- Estado (IDARE) y el Inventario de Recursos de Afrontamiento en la versión adaptada de Valdez (1999). Los resultados mostraron correlaciones inversas y significativas entre la ansiedad rasgo y los recursos cognitivos (r=0.33, p<.05), recursos sociales (r=.30, p<.05) recursos físicos (r=.26, p<.05), y el puntaje global de los recursos de afrontamiento (r=.29, p<.05). Los resultados demuestran una importante relación entre ambas variables, lo cual contribuye en el conocimiento acerca del funcionamiento de estos pacientes. / It has been demonstrated that trait anxiety and coping resources have significant repercussions in type II diabetes. The objective of this study is to become aware of the relation between both psychological variables in a group of patients with a type II diabetes diagnosis. The sample group is made up by 65 participants, between 40 and 80 years of age, from a hospital in Metropolitan Lima, and who took the Trait scale of the State-Trait Anxiety Inventory (STAI) and the Coping Resources Inventory in adapted version of Valdez (1999). The results showed inverse and important correlations between the trait anxiety and the cognitive coping resources (r=0.33, p<.05), social coping resources (r=.30, p<.05) physical coping resources (r=.26, p<.05), and the global score of the coping resources (r=.29, p<.05). The results show an important relationship between both variables, which contributes to the knowledge on these patients function. / Tesis

Forty-two non-diabetics whose glycated haemoglobin levels could not be explained by their levels of fasting glycaemia or glucose tolerance were identified as part of the Islington Diabetes Survey. Mean glycated haemoglobin levels that were high relative to their blood glucose levels (HIGH GLYCATORS) were found in 22 subjects whilst 20 subjects had low relative levels (LOW GLYCATORS). A repeat glucose tolerance test in 13 of the 42 subjects (7 high and 6 low glycators) showed that they remained categorised in the two groups four years after the discrepancy was identified. Mean blood glucose levels calculated from two 5-point diurnal profiles also failed to explain the glycated haemoglobin levels in the two groups. Further biochemical and haematological tests revealed that glycated albumin showed a better relationship with blood glucose levels than did glycated haemoglobin. Intra-erythrocyte glucose concentrations were significantly lower than the plasma glucose in the low glycators, whilst the levels of erythrocyte 2,3-diphosphoglycerate (a known catalyst of glycation) were significantly higher in the high glycators. These findings may partially explain the original discovery of low and high glycators. The effects of high fibre/low glucose and high glucose/low fibre diets on glycated proteins were studied in normal subjects. Only glycated albumin levels changed significantly, probably due to small changes in plasma glucose occurring on each diet, which were not mirrored by similar changes in the erythrocyte. When another group of normal subjects received 1 g vitamin C daily for three months, significant reductions in glycated albumin and glycated haemoglobin were observed, with the former being reduced to a greater extent. This suggests that vitamin C has the potential of being used therapeutically to reduce glycation. In conclusion, for normal subjects, glycated albumin is a more reliable indicator of blood glucose control than glycated haemoglobin.

An enzymatic and a novel capillary gas-liquid chromatographic assay have been developed and compared for the analysis of red blood cell sorbitol concentrations. Factors affecting the performance of both assays were investigated and the analytical conditions optimised. The enzyme assay was found to be accurate and precise but lacked specificity with at least xylitol also acting as a substrate. The capillary GLC assay was accurate and precise with the advantage of increased specificity for polyol determinations. The enzyme assay was used to determine the response of erythrocyte sorbitol content in a clinical trial of diabetics treated with oral Sorbinil a novel aldose reductase inhibitor. The sorbitol content was reduced and this trend was reversed upon cessation of Sorbinil treatment. The capillary GLC method was used to determine the daily effect of oral Sorbinil upon erythrocyte sorbitol and myo-inositol concentrations in a clinical trial with diabetic subjects. It was found that Sorbinil therapy reduced the raised erythrocyte sorbitol by 60% within the first 24 hours of treatment at a lower dose than used in previous studies. The erythrocyte myo-inositol content of diabetic subjects was not altered by Sorbinil therapy. However, it was found, for the first time, that the myo-inositol level in diabetics was found to be significantly different to healthy, normal non-diabetic subjects. The daily variation in erythrocyte sorbitol and myo-inositol in normal non-diabetic subjects was investigated. The levels were found to be very consistent both for individuals and as a group and were significantly different to the levels found in diabetic subjects. The activity of erythrocyte aldose reductase was found to be greater in diabetics compared to normals. Capillary GLC was used to confirm the erythrocyte accumulation of sorbitol upon incubation with glucose. The concentration of other components in the erythrocyte were seen to change upon glucose incubation. The increase of one component was initially identified by its retention as glucosamine. An attempt to correlate the erythrocyte aldose reductase activity with the degree of severity of subjects with diabetic neuropathy was unsuccessful. Further work is required to optimise the assay conditions. It is concluded that the erythrocyte sorbitol levels can be used in conjunction with other tests and clinical observations to manage the long term complications associated with diabetes. In particular, the enzyme assay may be of use as a screening test. The capillary GLC assay will be of most use in further studies to determine the polyol and carbohydrate changes and their role in the onset of neuropathy.

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2008. / Submitted by Guimaraes Jacqueline (jacqueline.guimaraes@bce.unb.br) on 2009-05-11T11:45:22Z No. of bitstreams: 1 2008_AngelicaAmorimAmato.pdf: 2144968 bytes, checksum: 0be7dca3570a2aded6a2c838981942df (MD5) / Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2009-05-11T13:17:37Z (GMT) No. of bitstreams: 1 2008_AngelicaAmorimAmato.pdf: 2144968 bytes, checksum: 0be7dca3570a2aded6a2c838981942df (MD5) / Made available in DSpace on 2009-05-11T13:17:37Z (GMT). No. of bitstreams: 1 2008_AngelicaAmorimAmato.pdf: 2144968 bytes, checksum: 0be7dca3570a2aded6a2c838981942df (MD5) Previous issue date: 2008 / As tiazolidinedionas (TZDs) melhoram a sensibilidade insulínica e a homeostase da glicose em diversos modelos animais de obesidade e diabetes, e também em humanos. Esses benefícios são atribuídos, em grande parte, aos efeitos antiinflamatórios da ativação do receptor gama ativado por proliferadores peroxissomais (PPARg). No entanto, a utilização clínica das TZDs é limitada por retenção hídrica, ganho ponderal e adipogênese, e recentemente tem sido relacionada a aumento da mortalidade cardiovascular e perda de massa óssea. O mecanismo desses efeitos não é completamente definido, mas acredita-se que possa envolver ativação suprafisiológica do PPARg, e até mesmo ações independentes da ativação do PPARg pelas TZDs. Essas limitações aumentaram o interesse pela identificação de ligantes de PPARg que mantenham os efeitos antiinflamatórios benéficos da ativação do receptor, sem os efeitos desfavoráveis das TZDs. Acredita-se que a ativação parcial e específica do PPARg, assim como sua modulação diferencial em tecidos distintos, possa ser mais efetiva e segura que a ativação completa e não seletiva pelas TZDs. Com o objetivo de identificar novos ligantes de PPARg, diversas benzilideno- e acridinilideno-TZDs sintéticas foram investigadas quanto à atividade agonista em PPAR por meio de ensaios de gene repórter em pró-monócitos humanos U-937. Somente o GQ-16 induziu a atividade transcricional do PPARg, e apresentou características de agonista parcial do receptor. Esse composto não ativou PPARa, -d ou RXRa, nem antagonizou a atividade transcricional do PPARg induzida pela rosiglitazona. Estudos in vitro mostraram que o GQ-16 se ligou diretamente ao domínio de ligação ao ligante do PPARg, com menor afinidade que a rosiglitazona e que, em concordância com seu efeito agonista, induziu a interação entre o PPARg e o coativador SRC-1. O GQ-16 também foi capaz de induzir a adipogênese em cultura de células, embora em menor intensidade que a rosiglitazona. Esses resultados indicam que o GQ-16 é um agonista parcial e seletivo do PPARg e apresenta menor potencial adipogênico, características que o distinguem das TZDs clássicas. As possíveis vantagens dessas características devem ser confirmadas por estudos in vivo. Além disso, a definição do modo de ligação do GQ-16 ao PPARg por estudos cristalográficos poderia contribuir para melhor compreensão dos determinantes da especificidade da ligação de ligantes entre os diferentes isotipos de PPARs e, assim, para o desenvolvimento de agonistas específicos de PPARg, possivelmente com efeitos mais favoráveis que os das TZDs clássicas. ______________________________________________________________________________________ ABSTRACT / Thiazolidinediones (TZDs) can improve whole body insulin sensitivity and ameliorate glucose metabolism in many animal models of obesity and diabetes, and also in humans. These beneficial effects are largely attributed to the antiinflammatory actions of activated peroxisome proliferator-activated receptor gamma (PPARg). Despite the established therapeutic value of TZDs, their clinical use is limited by fluid retention, weight gain and adipogenesis, and more recently these agents have been associated with increased cardiovascular mortality and bone loss. The mechanisms underlying these deleterious effects are not yet clear, but may be related to supraphysiological activation of PPARg, and also to PPARg independent actions of TZDs. These concerns have increased the interest for ligands which maintain the beneficial metabolic and anti-inflammatory effects of PPARg activation but mitigate the documented unfavorable effects of TZDs. There is evidence that partial and specific activation of PPARg, and also its selective modulation in different tissues, might be more effective and safe, in contrast to full and nonspecific activation by TZDs. Aiming to identify novel PPARg ligands, several synthetic benzilidene and acridinylidene TZDs were screened for PPAR agonist activity using reporter gene assay in U-937 human pro-monocytes. GQ-16 was the only novel TZD found to have agonist activity on PPARg, and displayed features of a partial agonist. It did not activate PPARa, -d or RXRa, neither influenced PPARg transcriptional activity induced by rosiglitazone. Competition assays showed GQ-16 bound directly to the ligand binding domain of PPARg with reduced affinity when compared to rosiglitazone. In support of GQ-16 agonist effect on PPARg transcriptional activity, glutatione-S-transferase pull-down experiments showed it induced the interaction between PPARg and SRC-1. The adipogenic potential of GQ-16 was less pronounced than that of rosiglitazone. Collectively, these results indicate GQ16 is a partial and specific agonist for PPARg with reduced adipogenic potential. These features differentiate this novel compound from TZDs currently used in clinical practice, and its potential therapeutic advantages should be confirmed by in vivo studies. In addition, although the exact binding mode of GQ-16 to PPARg still requires the resolution of a crystal structure, these results could provide insights into the determinants of ligand binding selectivity between PPARg and the other PPAR isotypes, and hence contribute to the development of new PPARg-selective ligands with improved specificity and metabolic effects.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2008. / Submitted by Ângela Christina (angelchris@bce.unb.br) on 2009-05-11T20:33:06Z No. of bitstreams: 1 2008_SandraSLemos_parcial.pdf: 55970 bytes, checksum: f9ee29cd66c9a5370631329103f16808 (MD5) / Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2009-05-12T13:36:47Z (GMT) No. of bitstreams: 1 2008_SandraSLemos_parcial.pdf: 55970 bytes, checksum: f9ee29cd66c9a5370631329103f16808 (MD5) / Made available in DSpace on 2009-05-12T13:36:47Z (GMT). No. of bitstreams: 1 2008_SandraSLemos_parcial.pdf: 55970 bytes, checksum: f9ee29cd66c9a5370631329103f16808 (MD5) Previous issue date: 2008-06 / Há um crescente aumento na incidência de portadores da Diabetes Mellitus (DM) devido ao estilo de vida inadequado, especialmente o sedentarismo e alimentação não saudável, que levam à diminuição da qualidade vida (QV). Através de questionário semi-estruturado qualiquantitativo, montado para este trabalho, tomando como referências o WHOQOL-BREF e o DQOL, verificou-se quais fatores, segundo os portadores de DM, interferem na sua QV. A amostra foi de 80 indivíduos, idade média de 60 anos (± 13), 66,25% eram mulheres, 87,5% diabetes tipo 2, média de 11 anos (±8) de diagnóstico, 67,5% usavam o sistema público para o atendimento de saúde. O nutricionista foi o profissional mais citado no acompanhamento da diabetes por 48,75%, e a dieta e a atividade física como parte do tratamento, por 80% e 70% respectivamente. Além de dados de seu perfil, solicitou-se aos respondentes listarem espontaneamente os fatores que interferem na sua QV; posteriormente foram apresentadas perguntas com variáveis específicas. Nestas questões havia uma escala intervalar proporcional com atribuições de valores numéricos crescentes de 1 a 5 que correspondia ao grau de interferência da variável (interfere nada a interfere muito) na QV do portador. Espontaneamente, os aspectos mais mencionados foram: alimentação 25%; 22,5% a situação financeira e os problemas domésticos; 17,5% o estresse e 12,5% os cuidados com a saúde e com a diabetes. Os menos mencionados, com 1,5% foram: injeções diárias, controle da glicemia, ter que fazer exames e necessidade de ser mais reservado. Dentre as variáveis específicas oferecidas, as mais destacadas foram: cuidados com alimentação, situação financeira, atividades físicas, o fato de ser diabético, a presença de dor. As menos citadas foram: relações familiares, estética física, comportamentos dos demais indivíduos, tempo livre. Porém, observou-se várias questões com heterogeneidade grande de respostas, em que categorias opostas foram muito citadas. Nestas, buscou-se observar quais as características foram determinantes nestes casos. Assim, destaca-se que a individualidade, a educação em diabetes, o apoio dos familiares e o trabalho interdisciplinar são pontos que devem ser trabalhados no atendimento aos portadores de diabetes. _______________________________________________________________________________________ ABSTRACT / The number of people with Diabetes Mellitus (DM) has been increasing due to an inappropriate lifestyle, highlights are physical inactivity and a non-healthy diet that lead to a decreased quality of life (QOL). The study was done using a semi-structured questionnaire designed to this search, taking as reference the WHOQOL-BREF and DQOL. The sample of 80 individuals with the average age of 60 years (± 13), 66.25% were women, 87.5% type 2 diabetes, average of 11 years (± 8) of diagnosis, 67.5% were using the public health system. The nutritionist was the professional most quoted in the monitoring process of diabetes by 48.75%. The diet and physical activity was quoted by 80% and 70% respectively as part of treatment. In addition to data from their personal profile, the respondents were asked to spontaneously list the factors that interfere in their QOL; after that the questions with specific variables were presented. In these questions there was an interval scale with numbers from 1 to 5. The numbers corresponded to the degree of interference of variable (interferes nothing to interfere a lot) in QOL of the patients. The factors most mentioned spontaneously were: eating 25%, financial situation and domestic problems 22.5%, stress 17.5% and the care with health and with diabetes 12.5%. The least mentioned were: daily injections, blood glucose control, have to do exams and need to be more reserved with 1.5%. Among the specific variables suggested, the most important were: care with eating, financial situation, physical activities, being a diabetic and pain. The least mentioned were: family relationships, physical aesthetics, attitudes of other individuals, free time. Many questions had a great diversity of responses, in which opposing categories were much cited. In these questions it was tried to find out what characteristics were decisive in these cases. Thus, it is important to note that the individuality, the education on diabetes, the support of family and interdisciplinary work are points that should be noted on the work with individuals with diabetes.

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A nefropatia diabética (ND) é uma complicação freqüente do diabete melito (DM) e acarreta grande morbi-mortalidade. A prevenção desta complicação será mais efetiva se os indivíduos de maior risco, que se beneficiariam de tratamento intensivo dos fatores risco modificáveis, fossem precocemente identificados. A microalbuminúria, definida por valores de excreção urinária de albumina (EUA) de 20-199 g/min, ainda é o melhor marcador da instalação e progressão da ND, além de ser um fator de risco para o desenvolvimento de doenças macrovasculares. Estas associações podem ser explicadas pela teoria de que a microalbuminúria representa, na verdade, dano endotelial generalizado. A albuminúria nos limites superiores da normalidade também está associada ao desenvolvimento futuro de micro- e macroalbuminúria. Além disso, existe uma associação entre albuminúria normal-alta, doença cardiovascular e mortalidade geral em indivíduos com e sem DM. A EUA tem correlação direta e contínua com o desenvolvimento de doença renal e cardiovascular, sem um ponto determinado a partir do qual ocorreria um aumento mais importante do risco. No entanto, na prática clínica se faz necessário o estabelecimento de um valor crítico para guiar o tratamento dos pacientes. Algumas evidências apontam para valores de EUA em torno de 10 g/min como um novo ponto de corte para o diagnóstico de microalbuminúria.Concluindo, a associação entre a EUA e os desfechos renais e cardiovasculares parece ser contínua e já está presente até mesmo com níveis de EUA considerados normais. A adoção do valor de 10 g/min como de risco poderá identificar os pacientes que deveriam receber tratamento mais precoce e agressivo dos fatores de risco modificáveis.

O diabetes melito é considerado uma doença crônica caracterizada pela hiperglicemia e por complicações macro e microangiopáticas. Entre as complicações microangiopáticas, a nefropatia diabética vem adquirindo cada vez mais importância por ser considerada uma causa de insuficiência renal que pode ocorrer a qualquer momento e afeta cerca de 40% dos pacientes diabéticos. A compreensão das mudanças moleculares e ultra-estruturais da proteinúria foi muito notada nos últimos anos e vários mecanismos foram propostos para explicar o dano renal. O que tem visto em comum entre todos é que os níveis de excreção urinária de albumina estão relacionados com a perda da capacidade de filtração seletiva da membrana basal glomerular do sistema renal. Isto acarreta o desenvolvimento de três estágios conhecidos na nefropatia diabética: a normoalbuminúria, microalbuminúria ou nefropatia incipiente e a macroalbuminúria ou nefropatia clínica.Portanto os métodos para a dosagem da albumina urinária em pequenas quantidades, mas excessivas em pacientes com diabetes melito tornaram-se fundamentalmente importante para evitar o desenvolvimento de transtornos angiopáticos. Além do mais, o tipo da coleta de amostra a ser utilizado para o procedimento destas dosagens tem sido relatado como um fator relacionado ao custo, praticidade e variações de resultados. Os métodos atualmente utilizados para screening, diagnóstico e monitoramento da nefropatia diabética possuem poucos resultados falso-negativos, baixo custo, reprodutibilidade e, portanto, são considerados adequados, entre eles a imunoturbidimetria tem sido o método de escolha. / Diabetes mellitus is considered a chronic disease characterized by the hyperglycemia and for macro and microangiopathic complications. Among the microangiopathic complications, the diabetic nephropathy is acquiring more importance along the years for being considered a cause of renal insufficiency that can occur at any time and affects about 40% of the diabetic patients. The comprehension of the molecular and ultra-structural changes of the proteinúria was very noticed in the past years and many mechanisms were considered to explain the renal damage. What all have in common is that the levels of albumin in urinary excretion is related with the loss of ability of selective filtration by the membrane basal glomerular of the renal system. This brings the development of three known stages in the diabetic nephropathy: the normoalbuminuria, microalbuminuria or incipient nephropathy and the macroalbuminuria or clinical nephropathy. Therefore the methods for the measurement of small amounts of urinary albumin, but extreme in diabetic patients, became essencial to avoid the development of angiopathic disturb. Besides that, the kind of sample used for these measurements procedures have been related as being a factor to the cost, practicability and variations in the results. The methods currently used for screening, diagnosis and monitoring diabetic nefropathy posses few false-negative results, low cost, reproducibility and therefore, are considered proper, among them; the immunoturbidimetry has been the choice method.

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Este trabalho visa a proporcionar subsídios para medir o grau de competência do diabético para o autocuidado. A escolha deste terra de pesquisa deve-se ao propósito do Serviço de Enfermagem de Saúde Pública (SESP) do Hospital de Clínicas de Porto Alegre (HCPA), de incluir nos Programas de Assistência de Enfermagem, uma sistemática de avaliação da assistência prestada. Para isto, adotou-se a "Escala para determinação da competência do diabético para o autocuidado"(ECDAC), desenvolvida por NUNES em 1982. Esta autora, utilizou o conceito de competência para o autocuidado, componente da teoria de Orem e as capacidades descritas por Backsheider como suporte teórico no desenvolvimento desta escala. Foram realizadas adaptações e a escala foi aplicada a uma população amostral de 100 indivíduos diabéticos adultos. A competência para o autocuidado foi medida utilizando-se a freqüência simples dos escores obtidos pelos indivíduos na escala. As correlações entre as características demográficas e individuais relacionadas a diabetes e a competência dos diabéticos para o autocuidado foram determinadas pelos teste t e análise de variância. Os resultados mostraram: a) correlação positiva entre a competência dos diabéticos para o autocuidado e o nível de escolaridade, a orientação recebida, o nº de internações provocadas pela diabetes, a idade, o estado civil, o sexo e o tipo de tratamento; b) correlação positiva entre a subescala que identificou as capacidades físicas do diabético e as que identificaram capacidades cognitivas e motivacionais. Finalmente com base nos resultados obtidos, coloca-se conclusões, implicações, limitações, assim como recomendações para desenvolvimento de futuras pesquisas que se relacionem com o tema deste estudo. / The purpose of this study was to raise support for measuring the grade of diabetics self care competence. This theme was chosen due to the purpose of includin in the programs of the Public Health Nursing Service, which belongs to the Clinics Hospital of Porto Alegre, a system to allow an evaluation of the Health Care given there. The "Diabetics Self Care Agency Scale" (ECDAC), developed in 1982 by NUNES was adopted for the study. The concept of Self Care Agency, a component of Orem's theory and the capabilities described and classified by Backsheider were utilized as theoretical support. The scale was adapted and administered to a sample of 100 diabetic adults. Self care agency was measured by the simple frequency of the scores obtained by the individuals in the scale. Correlations between demographic and individual caracteristics related to diabetes and the self care agency were determined by t test and variance analisys. Results showed that: a) positive correlation was found between self care agency of diabetic adults and the educational level, orientation received, the number of hospitalizations, age, marital status, sex and type of treatment; b) postive correlation was found between the subscales that identified physical capabilities and the ones that identified cognitive and motivational capabilities. Finally, based on the results obtained from this study, conclusions, implications and limitations were pointed out, as well as recommendations for further studies related to the theme.