By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

Indivíduos com hemoglobina glicada (HbA1c) &#8805;6,5% e níveis normais de glicemia têm maior risco de complicações relacionadas ao diabetes, em médio e longo prazo. Estas evidências foram importantes na recomendação de que HbA1c &#8805;6,5% fosse aceita como critério diagnóstico de diabetes. Diferenças raciais/ étnicas tem sido encontradas quanto aos níveis de HbA1c. Níveis elevados de HbA1c em indivíduos sem diabetes e com níveis normais de glicemia em jejum tem sido associados a alterações micro e macrovasculares, entre elas alterações da filtração glomerular. Diversos marcadores inflamatórios, em especial a MCP-1 (proteína quimiotática de macrófagos-1), estão envolvidos no mecanismo de lesão glomerular descrito em casos de nefropatia diabética No entanto, a HbA1C ainda não foi amplamente incorporada a rotina de diagnóstico e de acompanhamento na atenção primária brasileira. O objetivo deste estudo foi o de investigar a associação entre a alteração da HbA1c e da glicemia e fatores étnicos/ raciais e de risco cardiovascular e renal em adultos assistidos pelo Programa Médico de Família de Niterói, sem diagnóstico prévio de diabetes. Trata-se de um estudo transversal, onde foram reunidas informações de participantes do Estudo Cardio Metabólico Renal (CAMELIA), colhidas entre os meses de julho de 2006 a dezembro de 2007. Observou-se que o perfil de risco cardiovascular foi mais acentuado em indivíduos com alterações simultâneas da glicemia e da HbA1c. A alteração isolada da glicemia indicou ser condição de maior risco que a alteração isolada da HbA1c. Indivíduos com HbA1c &#8805; 6,5% eram em sua maioria mulheres de pele preta e apresentavam maiores níveis de LDL e creatinina sérica. Verificamos associação independente entre a alteração da HbA1c (&#8805; 5,7 e < 6,5% versus < 5,7%) e diminuição da taxa de filtração glomerular estimada. A HbA1c mostrou ser um marcador subclinico de alterações metabólicas em pacientes nao diabéticos e com glicemia de jejum < 126 mg/dL, em especial na população de mulheres e de indivíduos com a cor da pele preta. Os resultados apontam para a possibilidade de se utilizar a HbA1c como marcador de risco cardiovascular e renal visando propor estratégias de intervenção precoce e assim promover a prevenção de condições de agravos relacionados as alterações do metabolismo da glicose. / Individuals with glycated hemoglobin (HbA1c) &#8805; 6.5% and normal levels of blood glucose are at increased risk of complications related to diabetes. This evidence led to the American Diabetes Association (ADA) to recommend HbA1c &#8805; 6.5% as a criterion for the diagnosis of diabetes. Racial / ethnic differences have been found regarding HbA1c levels. Elevated HbA1c levels in individuals without diabetes and with normal fasting glucose levels have been associated with microvascular and macrovascular complications, including changes in glomerular filtration. Inflammatory markers, in particular MCP -1 ( macrophage chemotactic protein -1), are involved in the glomerular lesions described in cases of diabetic nephropathy mechanism However, this test has not been widely incorporated as a routine examination in primary care in Brazil. The objective os this study was to describe and analyse the association between changes in HbA1c and blood glucose, racial / ethnic factors and cardiovascular and renal risk in adults in adults assisted by the Family Doctor Program of Niteroi, with no previous medical diagnosis of diabetes. It is a cross sectional study, with information of CAMELIA Studys participants. Data was collected from July 2006 to December 2007. It was noted that the cardiovascular risk profile was more pronounced in individuals with concurrent changes in blood glucose and HbA1c. The cardiovascular risk of individuals with high levels of glycemia and normal HbA1c was greater than the risk of individuals with HbA1c&#8805;6,5% alone. Individuals with HbA1c &#8805; 6.5%, mostly women and black skin persons, had higher LDL and creatinine levels. Independent association between changes in HbA1c ( &#8805; 5.7 and < 6.5% versus < 5.7 % ) and decreased estimated glomerular filtration rate . HbA1c showed to be a subclinical marker of metabolic disorders in diabetic patients and not with fasting glucose < 126 mg / dL, especially in the population of women and individuals with black skin color. HbA1c showed to be a subclinical marker of metabolic disorders in diabetic patients and not with fasting glucose < 126 mg / dL , especially in the population of women and individuals with black skin color. The results point to the possibility of using HbA1c as a marker of cardiovascular and renal risk aiming to propose strategies for early intervention and thus promote the prevention of diseases and conditions related changes in glucose metabolism.

Indivíduos com hemoglobina glicada (HbA1c) &#8805;6,5% e níveis normais de glicemia têm maior risco de complicações relacionadas ao diabetes, em médio e longo prazo. Estas evidências foram importantes na recomendação de que HbA1c &#8805;6,5% fosse aceita como critério diagnóstico de diabetes. Diferenças raciais/ étnicas tem sido encontradas quanto aos níveis de HbA1c. Níveis elevados de HbA1c em indivíduos sem diabetes e com níveis normais de glicemia em jejum tem sido associados a alterações micro e macrovasculares, entre elas alterações da filtração glomerular. Diversos marcadores inflamatórios, em especial a MCP-1 (proteína quimiotática de macrófagos-1), estão envolvidos no mecanismo de lesão glomerular descrito em casos de nefropatia diabética No entanto, a HbA1C ainda não foi amplamente incorporada a rotina de diagnóstico e de acompanhamento na atenção primária brasileira. O objetivo deste estudo foi o de investigar a associação entre a alteração da HbA1c e da glicemia e fatores étnicos/ raciais e de risco cardiovascular e renal em adultos assistidos pelo Programa Médico de Família de Niterói, sem diagnóstico prévio de diabetes. Trata-se de um estudo transversal, onde foram reunidas informações de participantes do Estudo Cardio Metabólico Renal (CAMELIA), colhidas entre os meses de julho de 2006 a dezembro de 2007. Observou-se que o perfil de risco cardiovascular foi mais acentuado em indivíduos com alterações simultâneas da glicemia e da HbA1c. A alteração isolada da glicemia indicou ser condição de maior risco que a alteração isolada da HbA1c. Indivíduos com HbA1c &#8805; 6,5% eram em sua maioria mulheres de pele preta e apresentavam maiores níveis de LDL e creatinina sérica. Verificamos associação independente entre a alteração da HbA1c (&#8805; 5,7 e < 6,5% versus < 5,7%) e diminuição da taxa de filtração glomerular estimada. A HbA1c mostrou ser um marcador subclinico de alterações metabólicas em pacientes nao diabéticos e com glicemia de jejum < 126 mg/dL, em especial na população de mulheres e de indivíduos com a cor da pele preta. Os resultados apontam para a possibilidade de se utilizar a HbA1c como marcador de risco cardiovascular e renal visando propor estratégias de intervenção precoce e assim promover a prevenção de condições de agravos relacionados as alterações do metabolismo da glicose. / Individuals with glycated hemoglobin (HbA1c) &#8805; 6.5% and normal levels of blood glucose are at increased risk of complications related to diabetes. This evidence led to the American Diabetes Association (ADA) to recommend HbA1c &#8805; 6.5% as a criterion for the diagnosis of diabetes. Racial / ethnic differences have been found regarding HbA1c levels. Elevated HbA1c levels in individuals without diabetes and with normal fasting glucose levels have been associated with microvascular and macrovascular complications, including changes in glomerular filtration. Inflammatory markers, in particular MCP -1 ( macrophage chemotactic protein -1), are involved in the glomerular lesions described in cases of diabetic nephropathy mechanism However, this test has not been widely incorporated as a routine examination in primary care in Brazil. The objective os this study was to describe and analyse the association between changes in HbA1c and blood glucose, racial / ethnic factors and cardiovascular and renal risk in adults in adults assisted by the Family Doctor Program of Niteroi, with no previous medical diagnosis of diabetes. It is a cross sectional study, with information of CAMELIA Studys participants. Data was collected from July 2006 to December 2007. It was noted that the cardiovascular risk profile was more pronounced in individuals with concurrent changes in blood glucose and HbA1c. The cardiovascular risk of individuals with high levels of glycemia and normal HbA1c was greater than the risk of individuals with HbA1c&#8805;6,5% alone. Individuals with HbA1c &#8805; 6.5%, mostly women and black skin persons, had higher LDL and creatinine levels. Independent association between changes in HbA1c ( &#8805; 5.7 and < 6.5% versus < 5.7 % ) and decreased estimated glomerular filtration rate . HbA1c showed to be a subclinical marker of metabolic disorders in diabetic patients and not with fasting glucose < 126 mg / dL, especially in the population of women and individuals with black skin color. HbA1c showed to be a subclinical marker of metabolic disorders in diabetic patients and not with fasting glucose < 126 mg / dL , especially in the population of women and individuals with black skin color. The results point to the possibility of using HbA1c as a marker of cardiovascular and renal risk aiming to propose strategies for early intervention and thus promote the prevention of diseases and conditions related changes in glucose metabolism.

A disfunção erétil (DE) tem alta prevalência entre hipertensos e tem sido considerada marcador precoce de risco cardiovascular. A presença e gravidade da DE bem como a resposta clínica aos inibidores da fosfodiesterase tipo 5 (PDE5) parecem depender da biodisponibilidade do óxido nítrico (NO) endotelial e da extensão da doença aterosclerótica. O objetivo deste estudo foi avaliar a resposta clínica da vardenafila usada em dois regimes terapêuticos em hipertensos com DE vasculogênica e sem doença cardiovascular maior, correlacionando a gravidade da DE e a eficácia da vardenafila com dados antropométricos, laboratoriais, escore de risco cardiovascular e parâmetros vasculares funcionais e estruturais. A resposta clínica à vardenafila nos dois regimes foi avaliada conforme o percentual de respostas positivas à questão 3 do Perfil do Encontro Sexual (PES3). Os parâmetros vasculares considerados foram a espessura médio-intimal (EMI) da carótida comum, a dilatação mediada pelo fluxo (DMF) da artéria braquial e a dilatação nitrato-mediada (DNM). Foram incluídos 100 homens hipertensos com idade entre 50 e 70 anos, sendo 74 portadores de DE vasculogênica e 26 com função erétil normal que serviram de grupo controle. Nos pacientes com DE, o índice de massa corporal, relação cintura-quadril, EMI da carótida, níveis séricos de triglicerídeos, colesterol total e LDL foram significativamente maiores que no grupo controle. Após o uso de vardenafila on demand (fase 1), os pacientes com mais de 50% de respostas positivas ao PES3 ou 50% de respostas afirmativas e um incremento de 6 pontos ou mais em relação ao Índice Internacional de Função Erétil (IIEF-FE) basal e/ou resposta positiva a Questão de Avaliação Global (QAG), foram considerados respondedores. O escore do IIEF-FE basal se correlacionou negativamente com a EMI da carótida (r=-0,48, P<0,001) e com o escore de Framingham (r= -0,41, P<0,001) no grupo com DE. Houve forte correlação positiva entre a resposta clínica à vardenafila com a DMF (r= 0,70, P<0,001), que não se observou entre o sub-grupo de diabéticos. Os 35 pacientes considerados não-respondedores na fase 1 foram randomizados e, em desenho duplo-cego, receberam vardenafila ou placebo diariamente durante cinco semanas, podendo usar 10 mg de vardenafila uma hora antes da atividade sexual (fase2). Houve resposta clínica positiva em 38,8% dos que receberam a vardenafila na fase 2 e esta resposta se correlacionou com a frequência sexual (r= 0,68, P<0,01) e com o escore de Framingham (r= -0,65, P<0,01), com a EMI da carótida (r= -0,61, P=0,01) e com o LDL-colesterol (r= -0,64, P<0,01). A vardenafila foi bem tolerada em ambos os regimes terapêuticos. Concluímos que nessa amostra de hipertensos, a gravidade da DE foi relacionada a parâmetros vasculares estruturais (EMI), enquanto a resposta clínica à vardenafila on demand foi mais diretamente dependente da função vascular momentânea (DMF). Houve benefício na utilização de vardenafila diariamente com o objetivo de resgatar a eficácia do inibidor quanto à melhora do desempenho sexual. A falta de eficácia clínica ao inibidor da PDE5 em ambos os regimes terapêuticos pode servir como marcador clínico que identifica homens hipertensos com um risco cardiovascular aumentado. / Erectile dysfunction (ED) is a high prevalent disease in hypertensive subjects and has been considered an early cardiovascular risk marker. EDs presence and severity, as well as clinical response to phosfodiesterase type 5 (PDE5) inhibitors, vary according to nitric oxide (NO) availability and atherosclerosis extension. We investigated whether vasculogenic ED severity and clinical response to vardenafil used on demand or continuously were associated with structural and functional vascular changes in patients with uncomplicated hypertension. Our main efficacy criterion was per patient percentage of positive answers on Sexual Encounter Profile question 3(SEP3). Vascular parameters considered were intima-media thickness (IMT), flow-mediated dilation (FMD) on brachial artery and nitrate-mediated dilation. A total of 100 hypertensive men aging between 50 and 70 years were included. Among these patients, 74 had vasculogenic ED and 26 presented normal erectile function according to erectile domain of International Index of Erectile Function (IIEF-EF). Among those with ED, body mass index, waist-rip ratio, carotid IMT, triglycerides, total cholesterol and LDL-cholesterol were significantly higher than controls. After vardenafil on demand usage during phase 1, patients with more than 50% of positive answers on SEP3 or 50% and more than 6 points on IIEF basal score or positive answer to global evaliation question were considered responders. IIEF basal score correlated inversely with carotid IMT (r=-0.48, P<0.001) and with Framingham risk score (r= -0.41, P<0.001) in ED group. Clinical response to vardenafil strongly correlated with FMD (r= 0.70, P<0.001), except among diabetics. Non responders (n=35) on phase 1 were included on phase 2 when, after randomization, they received vardenafil 10 mg nightly or placebo during five weeks. Open vardenafil on demand were allowed one hour before sexual intercourse, and 38.8% of active group improved and became responders to vardenafil. Clinical response on phase 2 correlated with sexual frequency (r= 0.68, P<0.01), Framingham score (r= -0.65, P<0.01), carotid IMT (r= -0.61, P=0.01) and LDL-cholesterol (r= -0.64, P<0.01). We concluded that in hypertensive males with vasculogenic ED and no other clinical evidence of atherosclerosis, ED severity correlated with structural parameters (carotid IMT), while phosphodiesterase-5 effectiveness correlated with functional vascular aspects (brachial FMD). There were positive impact with continuous vardenafil on non responders to on demand regime and that could be an option to salvage strategy. Lack of PDE5 inhibitor efficacy in both therapeutic strategies could point out to higher cardiovascular risk and could be considered a useful clinical marker.

A disfunção erétil (DE) tem alta prevalência entre hipertensos e tem sido considerada marcador precoce de risco cardiovascular. A presença e gravidade da DE bem como a resposta clínica aos inibidores da fosfodiesterase tipo 5 (PDE5) parecem depender da biodisponibilidade do óxido nítrico (NO) endotelial e da extensão da doença aterosclerótica. O objetivo deste estudo foi avaliar a resposta clínica da vardenafila usada em dois regimes terapêuticos em hipertensos com DE vasculogênica e sem doença cardiovascular maior, correlacionando a gravidade da DE e a eficácia da vardenafila com dados antropométricos, laboratoriais, escore de risco cardiovascular e parâmetros vasculares funcionais e estruturais. A resposta clínica à vardenafila nos dois regimes foi avaliada conforme o percentual de respostas positivas à questão 3 do Perfil do Encontro Sexual (PES3). Os parâmetros vasculares considerados foram a espessura médio-intimal (EMI) da carótida comum, a dilatação mediada pelo fluxo (DMF) da artéria braquial e a dilatação nitrato-mediada (DNM). Foram incluídos 100 homens hipertensos com idade entre 50 e 70 anos, sendo 74 portadores de DE vasculogênica e 26 com função erétil normal que serviram de grupo controle. Nos pacientes com DE, o índice de massa corporal, relação cintura-quadril, EMI da carótida, níveis séricos de triglicerídeos, colesterol total e LDL foram significativamente maiores que no grupo controle. Após o uso de vardenafila on demand (fase 1), os pacientes com mais de 50% de respostas positivas ao PES3 ou 50% de respostas afirmativas e um incremento de 6 pontos ou mais em relação ao Índice Internacional de Função Erétil (IIEF-FE) basal e/ou resposta positiva a Questão de Avaliação Global (QAG), foram considerados respondedores. O escore do IIEF-FE basal se correlacionou negativamente com a EMI da carótida (r=-0,48, P<0,001) e com o escore de Framingham (r= -0,41, P<0,001) no grupo com DE. Houve forte correlação positiva entre a resposta clínica à vardenafila com a DMF (r= 0,70, P<0,001), que não se observou entre o sub-grupo de diabéticos. Os 35 pacientes considerados não-respondedores na fase 1 foram randomizados e, em desenho duplo-cego, receberam vardenafila ou placebo diariamente durante cinco semanas, podendo usar 10 mg de vardenafila uma hora antes da atividade sexual (fase2). Houve resposta clínica positiva em 38,8% dos que receberam a vardenafila na fase 2 e esta resposta se correlacionou com a frequência sexual (r= 0,68, P<0,01) e com o escore de Framingham (r= -0,65, P<0,01), com a EMI da carótida (r= -0,61, P=0,01) e com o LDL-colesterol (r= -0,64, P<0,01). A vardenafila foi bem tolerada em ambos os regimes terapêuticos. Concluímos que nessa amostra de hipertensos, a gravidade da DE foi relacionada a parâmetros vasculares estruturais (EMI), enquanto a resposta clínica à vardenafila on demand foi mais diretamente dependente da função vascular momentânea (DMF). Houve benefício na utilização de vardenafila diariamente com o objetivo de resgatar a eficácia do inibidor quanto à melhora do desempenho sexual. A falta de eficácia clínica ao inibidor da PDE5 em ambos os regimes terapêuticos pode servir como marcador clínico que identifica homens hipertensos com um risco cardiovascular aumentado. / Erectile dysfunction (ED) is a high prevalent disease in hypertensive subjects and has been considered an early cardiovascular risk marker. EDs presence and severity, as well as clinical response to phosfodiesterase type 5 (PDE5) inhibitors, vary according to nitric oxide (NO) availability and atherosclerosis extension. We investigated whether vasculogenic ED severity and clinical response to vardenafil used on demand or continuously were associated with structural and functional vascular changes in patients with uncomplicated hypertension. Our main efficacy criterion was per patient percentage of positive answers on Sexual Encounter Profile question 3(SEP3). Vascular parameters considered were intima-media thickness (IMT), flow-mediated dilation (FMD) on brachial artery and nitrate-mediated dilation. A total of 100 hypertensive men aging between 50 and 70 years were included. Among these patients, 74 had vasculogenic ED and 26 presented normal erectile function according to erectile domain of International Index of Erectile Function (IIEF-EF). Among those with ED, body mass index, waist-rip ratio, carotid IMT, triglycerides, total cholesterol and LDL-cholesterol were significantly higher than controls. After vardenafil on demand usage during phase 1, patients with more than 50% of positive answers on SEP3 or 50% and more than 6 points on IIEF basal score or positive answer to global evaliation question were considered responders. IIEF basal score correlated inversely with carotid IMT (r=-0.48, P<0.001) and with Framingham risk score (r= -0.41, P<0.001) in ED group. Clinical response to vardenafil strongly correlated with FMD (r= 0.70, P<0.001), except among diabetics. Non responders (n=35) on phase 1 were included on phase 2 when, after randomization, they received vardenafil 10 mg nightly or placebo during five weeks. Open vardenafil on demand were allowed one hour before sexual intercourse, and 38.8% of active group improved and became responders to vardenafil. Clinical response on phase 2 correlated with sexual frequency (r= 0.68, P<0.01), Framingham score (r= -0.65, P<0.01), carotid IMT (r= -0.61, P=0.01) and LDL-cholesterol (r= -0.64, P<0.01). We concluded that in hypertensive males with vasculogenic ED and no other clinical evidence of atherosclerosis, ED severity correlated with structural parameters (carotid IMT), while phosphodiesterase-5 effectiveness correlated with functional vascular aspects (brachial FMD). There were positive impact with continuous vardenafil on non responders to on demand regime and that could be an option to salvage strategy. Lack of PDE5 inhibitor efficacy in both therapeutic strategies could point out to higher cardiovascular risk and could be considered a useful clinical marker.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O diabetes mellitus(DM) e as disfunções tireoidianas(DT) são as duas desordens endocrinológicas mais comuns na prática clínica. A DT não reconhecida pode interferir no controle metabólico e adicionar mais risco a um cenário predisponente à doença cardiovascular. O objetivo deste estudo foi avaliar a prevalência da DT em pacientes com diabetes mellitus tipo 1 e tipo 2 (DM1 e DM2) e avaliar o risco cardiovascular em pacientes com DM2 com e sem DT utilizando parâmetros clínicos e laboratoriais. Trata-se de um estudo observacional de corte transversal. Foram avaliados 304 pacientes com DM2 e 82 pacientes com DM1. Os pacientes foram submetidos a um inquérito clínico-demográfico e avaliação laboratorial para determinação do perfil lipídico, glicídico e da função tireoidiana. Os pacientes com DM2 tiveram seus escores de risco cardiovascular em 10 anos determinados pelas equações de Framingham e do UKPDS risk engine. A frequência de disfunção tireoidiana entre os 386 pacientes foi de 14,7%, sendo de 13% nos que não possuíam disfunção prévia. A disfunção mais frequente encontrada foi de hipotireoidismo subclínico, com 13% no DM1 e de 12% no DM2. A prevalência de anticorpos anti-tireoperoxidase (TPO) positivos foi de 10,8%, sendo de14,6% em pacientes com DM1.Foram diagnosticados 44 (11,2%) novos casos de disfunção tireoidiana em pacientes que negavam ou desconheciam terem DT prévia.Destes novos casos, 12,8% em DM1 e 13,1% em DM2.Dos 49 pacientes com DT prévia, 50% dos DM1e 76% dos DM2 estavam compensados. Não foi observada diferença entre as médias do escore de risco de Framingham entre os pacientes DM2 com eutireoidismo e com hipotireoidismo subclínico. Observou-se uma associação entre o hipotireoidismo subclínico e risco cardiovascular nos pacientes com DM2 demonstrado pela diferença estatisticamente significativa entre as médias do escore UKPDS para doença coronariana não-fatal e fatal, acidente vascular cerebral fatal entre os dois grupos (p=0,007; 0,005;0,027 respectivamente). As demais funções tireodianas (hipotireoidismo clínico, hipertireoidismo clínico e subclínico) encontradas não foram analisadas devido ao pequeno número de pacientes em cada grupo.Concluímos que o rastreio da doença tireoidiana entre os pacientes com diabetes mellitus deve ser realizado rotineiramente considerando-se a prevalência de novos casos de DT diagnosticados e o fato de que os pacientes com DM2 e com hipotireoidismo subclínico avaliados possuírem um risco cardiovascular maior. Todavia, concluímos que estudos prospectivos e com maior número de pacientes são necessários para o esclarecimento do impacto da doença tireoidiana no risco cardiovascular do paciente com DM. / Diabetes mellitus and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The unrecognized TD may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective of this study was to evaluate the prevalence of TD in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM) and to evaluate the cardiovascular risk of patients with T2DM with and without thyroid dysfunction using clinical and laboratory parameters. This is an observational cross-sectional study. We evaluated 304 patients with T2DM and 82 patients with T1DM. The patients underwent a clinical-demographic survey and laboratory evaluation to determine the lipid and glycemic profile and thyroid function. Patients with T2DM had their 10 years cardiovascular risk scores determined by Framingham equations and the UKPDS risk engine. The frequency of TD among the 386 patients was 14.7% and 13% who denied previous TD. The most frequently TD was subclinical hypothyroidism, in 13% of patients with T1DM and in 12% of patients with T2DM.The prevalence of anti-TPO antibodies was 10.8%, being more frequently among patients with T1DM (14.6%). Forty-four (11.2%) new cases of TD were diagnosed during the study in patients who denied or were unaware of this clinical condition. Of the 49 patients with prior TD,50% of the T1DM and 76% of T2DM were compensated. No differencies were observed between the mean scores of the Framingham risk among patients with T2DM who had normal thyroid function compared to those with subclinical hypothyroidism. An association between subclinical hypothyroidism and cardiovascular risk in T2DM patients was found by statistically significant difference between the mean UKPDS scores for non-fatal and fatal CHD and fatal stroke between the two groups (p = 0,007;0,005;0027; respectively). The other TD (clinical hypothyroidism, clinical and subclinical hyperthyroidism) found were not analyzed due to the small number of patients in each group.We conclude that screening for thyroid disease among patients with diabetes mellitus should be routinely performed considering the prevalence of new cases diagnosed and the fact that patients with DM2 and subclinical hypothyroidism evaluated had a higher cardiovascular risk. However, prospective studies and with more patients are warranted to determine the impact of thyroid dysfunction in the cardiovascular risk of patients with diabetes.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Recent studies indicate a strong association among physical inactivity, low level of cardio-respiratory fitness and the presence of cardiovascular risk factors such as high blood pressure, diabetes and obesity. Medicine and Physical Education students are involved in the field of health rehabilitation, promotion and conservation, being physical activity a priority intervention to achieve this goal. However, little is known about the adoption of physical activity as part of the life style of Medicine and Physical Education students. The main goal of this paper is to compare the level of physical activity, the level of cardio-respiratory fitness and the cardiovascular risk in students of Medicine and Physical Education. The data collection took place at the Physical Education Department at the Federal University of Sergipe. In a first stage, the IPAQ questionnaire was applied to quantify the amount of physical activity in 126 students from the 7th and 8th periods of Medicine and Physical Education courses. In a second stage, 40 students were randomly selected, 20 from each course, to evaluate cardiovascular risk factors and cardio-respiratory fitness. We measured (a) blood pressure; (b) body mass index (BMI); (c) fat percentage (electrical bioimpedance); (d) waist circumference (WC); (e) biochemical lab tests and (f) cardio-respiratory fitness (Kline test). Comparing Medicine students versus Physical Education students, we noticed a higher frequency of subjects presenting: low level of physical activity (55 vs 15%; p=0,008); pre-high blood pressure by SBP (80 vs 25%; p=0,000) and by DBP (45 vs 5%; p=0,003); overweight (50 vs 10%; p=0,006); waist circumference (25 vs 0%; p=0,017); elevated total cholesterol (165±28 vs 142±28mg/dL; p=0,015); high LDLc (99±27 vs 81±23 mg/dL; p=0,026); high glycemia (81±8 vs 75±7 mg/dL; p=0,013); lower cardio-respiratory fitness (48±8 vs 56±7 L.min.-1; p=0,001). Even though the knowledge that practicing physical activities is an important preventive intervention for cardiovascular diseases, students of Medicine display a smaller amount of physical activities practice, lower level of cardio-respiratory fitness and, most importantly, higher frequency of cardiovascular risk, compared to those of Physical Education. / Estudos recentes indicam forte associação entre inatividade física, baixo nível de condicionamento cardio-respiratório e presença de fatores de risco cardiovascular como hipertensão arterial, diabetes e obesidade. O ensino da Medicina e da Educação Física está fundamentado com o campo da conservação, promoção e reabilitação da saúde, sendo a atividade física uma intervenção prioritária para este fim. Entretanto, pouco se sabe sobre a adoção da atividade física como parte do estilo de vida dos estudantes de Medicina e Educação Física. O objetivo principal do presente trabalho foi de comparar o nível de atividade física, o nível de condicionamento cardio-respiratório e o risco cardiovascular entre estudantes de Medicina e de Educação Física. A coleta de dados foi realizada no departamento de Educação Física da Universidade Federal de Sergipe. Em uma primeira etapa aplicou-se questionário IPAQ para quantificar atividade física em 126 alunos dos 7os e 8os períodos dos cursos de Educação Física e Medicina. Em uma segunda etapa, selecionou-se por intermédio de randomização, 40 alunos, 20 de cada curso, para avaliação de fatores de risco cardiovascular e avaliação do condicionamento cardio-respiratório. Foram mensurados: (a) pressão arterial; (b) índice de massa corpórea (IMC); (c) % de gordura (bioimpedância elétrica); (d) circunferência de cintura (CC), (e) testes bioquímicos laboratoriais e (f) condicionamento cardio-respiratório (Teste de Kline). Comparando-se estudantes de Medicina vs Educação Física foi observado maior freqüência de indivíduos apresentando: baixo nível de atividade física (55 vs 15%; p=0,008); pré-hipertensão pela PAS (80 vs 25%; p=0,000) e pela PAD (45 vs 5%; p=0,003); sobrepeso (50 vs 10%; p=0,006); circunferência de cintura (25 vs 0%; p=0,017); colesterol total elevado (165±28 vs 142±28 mg/dL; p=0,015); LDLc elevado (99±27 vs 81±23 mg/dL; p=0,026); glicemia elevada (81±8 vs 75±7 mg/dL; p=0,013); menor condicionamento cardio-respiratório (48±8 vs 56±7 ml/Kg/min; p=0,001). Apesar do conhecimento de que a prática de atividade física é uma importante intervenção preventiva para as doenças cardiovasculares, estudantes de Medicina apresentam menor quantitativo de prática de atividade física, menor nível de condicionamento cardio-respiratório e, mais importante, maior freqüência dos fatores de risco cardiovascular, comparados aos de Educação Física.

Made available in DSpace on 2014-07-29T15:29:19Z (GMT). No. of bitstreams: 1 Dissertacao CARLA FERREIRA.pdf: 3775197 bytes, checksum: bdad663383a24c725cbe0056da09f27e (MD5) Previous issue date: 2009-12-08 / Introduction: cardiovascular risk factors (CVRFs) are highly prevalent in and have an impact on elderly people s morbidity and mortality which is still unknown among elderly users of the National Health System (SUS). Objective: to investigate the prevalence of CVRFs in elderly basic care users in the Goiânia, Goiás SUS. Methodology: a cross-sectional study with multi-stage sampling; a household survey of 418 people over 60 years old who were SUS basic care users in Goiânia. Socio-economic, demographic, lifestyle, weight, height, waist circumference, blood pressure and medication use data were collected. The CVRFs under investigation were arterial hypertension, diabetes mellitus, total obesity, central obesity, dyslipedemias, smoking, sedentarism and alcohol consumption. The Chi-square test was used to analyze associations at a 5% level of significance. Results: the prevalences for CVRFs were 80.4% for arterial hypertension, 83.3% for central obesity, 59.8% for sedentarism, 32.2% for total obesity, 23.4% for dyslipidemias, 19.1% for diabetes mellitus, 10.0% for smoking and 5.9% for alcohol consumption. As far simultaneity is concerned, 2.4% of the elderly did not present any CVRFs. The simultaneity of three or more CVRFs occurred in 65% of the elderly people in the study and was more frequent among women. Conclusion: the CVRFs occurred simultaneously in more than half of the elderly under study. The most prevalent CVRFs were arterial hypertension, central obesity and sedentarism. It is necessary to intensify health promotion and cardiovascular disease prevention strategies among elderly users of SUS basic care in Goiânia, mainly among those with CVRF simultaneity. / Introdução: os fatores de risco cardiovascular (FRCV) apresentam alta prevalência e causam impacto na morbimortalidade de idosos, ainda desconhecido entre idosos usuários do Sistema Único de Saúde. Objetivo: investigar a prevalência de FRCV em idosos usuários da atenção básica do Sistema Único de Saúde (SUS) de Goiânia-Goiás. Metodologia: estudo transversal com amostragem em múltiplos estágios, realizado por meio de inquérito domiciliar com 418 idosos acima de 60 anos, usuários do SUS da atenção básica de Goiânia. Foram coletados dados socioeconômicos, demográficos, estilo de vida, peso, altura, circunferência da cintura, pressão arterial e uso de medicamentos. Os FRCV investigados foram: hipertensão arterial, diabetes mellitus, obesidade total, obesidade central, dislipidemias, tabagismo, sedentarismo e consumo de bebida alcoólica. Utilizou-se o teste do Qui quadrado para análises das associações, com significância de 5%. Resultados: as prevalências dos FRCV foram 80,4% de hipertensão arterial, 83,3% de obesidade central, 59,8% de sedentarismo, 32,2% de obesidade total, 23,4% de dislipidemias, 19,1% de diabetes mellitus, 10,0% de tabagismo e 5,9% de consumo de bebida alcoólica. Quanto à simultaneidade 2,4% dos idosos não apresentaram nenhum FRCV. A simultaneidade de três ou mais FRCV ocorreu em 65% dos idosos, sendo mais freqüente entre as mulheres. Conclusão: os FRCV ocorrem de forma simultânea em mais da metade dos idosos, sendo que os mais prevalentes foram hipertensão arterial, obesidade central e sedentarismo. É preciso intensificar as estratégias de promoção da saúde e prevenção de agravos cardiovasculares em idosos usuários da atenção básica do SUS de Goiânia, principalmente entre aqueles com simultaneidade de FRCV.