Cheng Sze-Lok Alfred. / "March 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 175-211). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

In many African countries, including South Africa, much attention has been centred on the management of HIV/AIDS and tuberculosis epidemics. However, there is growing awareness in South Africa that life-style related non-communicable conditions, such as diabetes and obesity, represent an important health priority (Pirie, 2005:42). The general objective of this study was to evaluate the treatment of diabetic patients in clinics on primary healthcare level and to determine what contributions can be made in the prevention of diabetic complications. The research method consisted out of the selection of the study population, data collection (questionnaire) and the data analysis. There was no structural way of deciding which patients would be selected to be interviewed. As the patients arrived for their appointments the interviewer was informed. No patient was forced to participate in this study and after they agreed to the interview, they signed a consent form that releases the University of any liability that may occur and to give their permission for the interview. The questionnaire was compiled which covered all the aspects of diabetes. This included diagnostic data, life-style, well-being, compliance and monitoring. The researcher completed the questionnaires whilst interviewing the patients. The data obtained from the questionnaires were statistically analysed by using the Statistical Analysis System, SAS 9.1. Effect size, which was given by the Phi coefficient, was used as a descriptive statistic. In this particular study population, the majority of patients were classified as type 2 diabetics. This can be viewed in table 4.8 where 62.14% of the total study population was classified as group B, which means that these patients use oral glucose lowering drugs to control their disease. A further 33.98% of the population was classified as group C diabetics, which means that these patients need oral glucose lowering drugs as well as exogenous insulin to maintain a healthy life. The latter group obviously consists of patients whose diabetic status was not under control in the past, thus the need for the insulin. This clearly shows that these patients have not been informed about how they can manage the disease by dietary modification and lifestyle interventions. Lifestyle, socio-economic and education played a major role in the development of this disease in these patients. The weight status of the study population was determined and can be viewed in table 4.15. Only 20.39% of them were of normal weight with a body mass index (BMI) ranging between 18.5 - 24.9 kg/m2. 39.81% of them were overweight with their BMI ranging between 25 - 29.9 kg/m2 and the remaining 39.81% of the study population were classified as obese with their BMI's above 30 kg/m2. The majority (an estimated 80%) of the study population were above optimal weight. This may cause the development of chronic complications, such as retinopathy, neuropathy and nephropathy. The socio-economic status of the study population was relatively poor because of unemployment. Although 90.07% of them said they had no difficulty to follow their diet (table 4.56) almost half of the patients said they had some difficulty to get the correct food for their specific needs (table 4.53). The first may be because they are still eating they way they used to with no modifications and the latter may be because of their financial status. Not being able to find work has a major effect on their lives. They cannot afford to buy foods suitable for their needs. As previously stated, patient education is fundamental in the managing and controlling diabetes. When these patients were asked whether they know what diabetes is, and what the complications of the disease might hold, most of them answered that it means they have 'sugar', and cannot eat sugary foods any more. This clearly indicates that they did not have a complete knowledge of their disease. After having explained to them in uncomplicated terms what the disease implicates, many of them said it had not been not explained to them previously and that they now understood it better. It was concluded that the majority of the studied population were under a false impression of what diabetes implied. This is partly due to the lack of time the clinic staffs have to spend with each patient, educating them about the disease. One aspect that was most obvious during this study was the fact that an estimated 20% of all patients studied had their own blood glucose monitor (table 4.80). This is somewhat concerning because to have optimal control over one's blood glucose levels, one needs to has a blood glucose monitor for regular monitoring. An estimated 70% of the studied population measures their blood glucose only once a month when they attend the clinic for their monthly visit (table 4.81). This is not nearly enough to ensure optimal control. The average blood glucose levels were calculated and described in section 4.7. Even with the minimal measurement, about 50% of these patients' blood glucose levels were fairly under control with an average of 6-9mmol/L (table 4.88). But the other estimated 50% of the population were not controlled with averages of either below 5mmol/L or above 9mmol/L. This is concerning because the possibility that these uncontrolled cases may develop chronic complications, might be unavoidable unless they start taking control of their lives. And for this to happen, these patients need all the possible education from qualified health care providers and the support of their families. Certain recommendations and restrictions were formulated and discussed. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.

In many African countries, including South Africa, much attention has been centred on the management of HIV/AIDS and tuberculosis epidemics. However, there is growing awareness in South Africa that life-style related non-communicable conditions, such as diabetes and obesity, represent an important health priority (Pirie, 2005:42). The general objective of this study was to evaluate the treatment of diabetic patients in clinics on primary healthcare level and to determine what contributions can be made in the prevention of diabetic complications. The research method consisted out of the selection of the study population, data collection (questionnaire) and the data analysis. There was no structural way of deciding which patients would be selected to be interviewed. As the patients arrived for their appointments the interviewer was informed. No patient was forced to participate in this study and after they agreed to the interview, they signed a consent form that releases the University of any liability that may occur and to give their permission for the interview. The questionnaire was compiled which covered all the aspects of diabetes. This included diagnostic data, life-style, well-being, compliance and monitoring. The researcher completed the questionnaires whilst interviewing the patients. The data obtained from the questionnaires were statistically analysed by using the Statistical Analysis System, SAS 9.1. Effect size, which was given by the Phi coefficient, was used as a descriptive statistic. In this particular study population, the majority of patients were classified as type 2 diabetics. This can be viewed in table 4.8 where 62.14% of the total study population was classified as group B, which means that these patients use oral glucose lowering drugs to control their disease. A further 33.98% of the population was classified as group C diabetics, which means that these patients need oral glucose lowering drugs as well as exogenous insulin to maintain a healthy life. The latter group obviously consists of patients whose diabetic status was not under control in the past, thus the need for the insulin. This clearly shows that these patients have not been informed about how they can manage the disease by dietary modification and lifestyle interventions. Lifestyle, socio-economic and education played a major role in the development of this disease in these patients. The weight status of the study population was determined and can be viewed in table 4.15. Only 20.39% of them were of normal weight with a body mass index (BMI) ranging between 18.5 - 24.9 kg/m2. 39.81% of them were overweight with their BMI ranging between 25 - 29.9 kg/m2 and the remaining 39.81% of the study population were classified as obese with their BMI's above 30 kg/m2. The majority (an estimated 80%) of the study population were above optimal weight. This may cause the development of chronic complications, such as retinopathy, neuropathy and nephropathy. The socio-economic status of the study population was relatively poor because of unemployment. Although 90.07% of them said they had no difficulty to follow their diet (table 4.56) almost half of the patients said they had some difficulty to get the correct food for their specific needs (table 4.53). The first may be because they are still eating they way they used to with no modifications and the latter may be because of their financial status. Not being able to find work has a major effect on their lives. They cannot afford to buy foods suitable for their needs. As previously stated, patient education is fundamental in the managing and controlling diabetes. When these patients were asked whether they know what diabetes is, and what the complications of the disease might hold, most of them answered that it means they have 'sugar', and cannot eat sugary foods any more. This clearly indicates that they did not have a complete knowledge of their disease. After having explained to them in uncomplicated terms what the disease implicates, many of them said it had not been not explained to them previously and that they now understood it better. It was concluded that the majority of the studied population were under a false impression of what diabetes implied. This is partly due to the lack of time the clinic staffs have to spend with each patient, educating them about the disease. One aspect that was most obvious during this study was the fact that an estimated 20% of all patients studied had their own blood glucose monitor (table 4.80). This is somewhat concerning because to have optimal control over one's blood glucose levels, one needs to has a blood glucose monitor for regular monitoring. An estimated 70% of the studied population measures their blood glucose only once a month when they attend the clinic for their monthly visit (table 4.81). This is not nearly enough to ensure optimal control. The average blood glucose levels were calculated and described in section 4.7. Even with the minimal measurement, about 50% of these patients' blood glucose levels were fairly under control with an average of 6-9mmol/L (table 4.88). But the other estimated 50% of the population were not controlled with averages of either below 5mmol/L or above 9mmol/L. This is concerning because the possibility that these uncontrolled cases may develop chronic complications, might be unavoidable unless they start taking control of their lives. And for this to happen, these patients need all the possible education from qualified health care providers and the support of their families. Certain recommendations and restrictions were formulated and discussed. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.

Chronic haemodialysis patients have a high prevalence of Hepatitis B and C virus infections both of which are associated with chronic liver disease and hepatocellular carcinoma Hepatitis B virus (HBV) was identified as a frequent cause of hepatitis during the early years of chronic haemodialysis therapy and strict adherence to infection control measures alone proved inadequate to control the transmission of infection between patients. A policy of regular screening of all patients and blood donations for hepatitis B surface antigen together with isolation of positive patients to separate dialysis units resulted in a significant decline in the incidence of new infections. Hepatitis B vaccination provided an important new means of protection. Despite the finding that haemodialysis patients did not respond to the vaccine as well as normal adults, randomized controlled trials showed significant protection in units with a previously high incidence of infection. Studies have identified both monocyte dysfunction and B cell inhibition by elevated levels of parathyroid hormone (PTH) as possible mechanisms for the reduced response in dialysis patients. Other factors which have been associated with this poor response include increased age, male gender, specific human leukocyte antigens, shorter time on a dialysis programme and poor nutritional status. One study has shown an increased response in patients receiving recombinant human erythropoietin and. there is in vitro evidence that nifedipine improves B cell proliferation in dialysis patients with hyperparathyroidism. Hepatitis C virus (HCV) infection in haemodialysis patients has been associated with blood transfusions in many studies. However, evidence exists that transmission between patients also occurs. There is disagreement as to what measures are necessary to prevent possible nosocomial spread. Some authors recommend isolation of HCV -infected patients to separate dialysis machines or units. There is also concern over the potential of dialyzer reuse to transmit the virus. A protocol for surveillance 0f hepatitis B and C infections was established in the dialysis unit at Groote Schuur Hospital while HCV positive patients were not isolated and reuse of dialyzers was continued for all patients. HBV -infected patients are dialyzed in a separate unit and their dialyzers are not reused. A trial of hepatitis B vaccination of all antibody negative patients was undertaken using four doses of a plasma-derived vaccine given intramuscularly at month 0,1 ,2 and 4.

O diabetes mellitus é considerado um dos problemas de saúde globalmente mais desafiadores do século 21. De acordo com as estimativas recentes do International Diabetes Federation - IDF, cerca de 382 milhões de pessoas são diabéticas e esse número tende a aumentar para além de 592 milhões em menos de 25 anos. Para melhor compreensão do Diabetes mellitus e suas complicações torna-se necessário buscar novos marcadores para a doença. O DM promove estresse oxidativo, inflamação e a formação de produtos avançados de glicação não enzimática (AGES), o que leva a dano tecidual no paciente diabético. Marcadores de dano oxidativo em proteínas e lipídeos na vigência do DM têm sido amplamente abordados na literatura, no entanto o estudo de lesões em DNA ainda requer mais atenção em modelos in vivo. Este trabalho teve como objetivo avaliar o dano oxidativo e resultante de glicação avançada em rim, fígado, cerebelo, sangue e urina de animais diabéticos, assim como a modulação do dano por diferentes períodos de tratamento com insulina, a fim de verificar se o controle da glicemia nos animais diabéticos protege contra a indução dos danos em biomoléculas. Para a indução do DM nos ratos Sprague-Dawley foram administrados 40 mg de STZ por kg de peso corpóreo por via intravenosa. Os níveis de MDA e 5-metildC foram avaliados por HPLC-DAD. A quantificação de HbA1c e dos adutos 1,N2-εdGuo, 1,N6-εdAdo, 8-oxodG e CEdG foi realizada por sistema HPLC-ESI-MS/MS. Os níveis de nitrito sérico foram determinados por leitura da absorbância em espectrofotômetro e a concentração de creatinina plasmática foi determinada por analisador bioquímico. Os resultados mostraram que as alterações metabólicas desencadeadas pela condição de hiperglicemia persistente não são prontamente revertidas após o controle da glicemia. Os níveis glicêmicos e de HbA1c apresentam diferença significativa entre os grupos de animais hiperglicêmicos e sadios, sendo observada uma queda dos valores de HbA1c somente a partir do tratamento com insulina por 6 semanas. Em plasma, rim e fígado as concentrações de MDA seguem o perfil de concentração de hemoglobina glicada (HbA1c), indicando que os eventos de glicação e estresse oxidativo podem estar relacionados. O controle glicêmico também apresentou efeito benéfico para a excreção de CEdG e 1,N6-εdAdo em urina, apesar de ser observado a partir dos níveis de 8- oxodG que a hiperinsulinemia leva a um quadro de estresse oxidativo. As três lesões são geradas por vias distintas: glicação avançada, peroxidação lipídica e ROS. Portanto, além do controle glicêmico, é importante que se desenvolvam estratégias de intervenção nas vias bioquímicas alteradas pela condição de hiperglicemia, a fim de reduzir os riscos das complicações decorrentes do diabetes mellitus. / Diabetes mellitus is generally considered one of the most challenging health problems of the 21st century. According to recent estimates from the International Diabetes Federation - IDF, about 382 million people have diabetes and this number is expected to increase beyond 592 million in less than 25 years. For a better understanding of diabetes mellitus and its complications becomes necessary to search for new biomarkers for the disease. The DM promotes oxidative stress, inflammation and the formation of advanced glycation end products (AGEs), which leads to tissue damage in the diabetic patient. Markers of oxidative damage to proteins and lipids in the presence of DM have been widely discussed in literature, however the study of DNA lesions in vivo models still requires more attention. This study aimed to evaluate the oxidative damage and advanced glycation in the kidney, liver, cerebellum, blood and urine of diabetic animals, as well as damage modulation for different periods of insulin treatment in order to verify that the glycaemic control in diabetic animals protects against induction of biomolecules damage. For induction of diabetes in Sprague-Dawley rats were administered 40 mg STZ per kg body weight intravenously. MDA and 5-metildC were evaluated by HPLC-DAD. The quantification of HbA1c and adducts 1,N2-εdGuo, 1,N6-εdAdo, 8-oxodG and CEdG was performed by HPLC-ESI-MS / MS system. The serum nitrite was determined by reading the absorbance in a spectrophotometer and the plasma creatinine concentration was determined by biochemical analyzer. The results showed that metabolic changes triggered by the condition of persistent hyperglycemia are not readily reversed after glycemic control. Blood glucose and HbA1c levels are significantly different between the groups of hyperglycemic and healthy animals, and was observed a fall in HbA1c only from insulin treatment for 6 weeks. In plasma, kidney and liver concentrations follow the profile of MDA concentration of glycated hemoglobin (HbA1c), indicating that the events of glycation and oxidative stress may be related. Glycemic control also showed beneficial effect for urine excretion of CEdG and 1,N6-εdAdo despite could be seen from 8-oxodG levels that the hyperinsulinaemia leads to a frame of oxidative stress. The three lesions are generated by distinct pathways: advanced glycation, lipid peroxidation and ROS. Therefore, beyond glycaemic control, it is important to develop intervention strategies in biochemical pathways altered by the condition of hyperglycemia in order to reduce the complications risk of diabetes mellitus.

O diabetes mellitus é considerado um dos problemas de saúde globalmente mais desafiadores do século 21. De acordo com as estimativas recentes do International Diabetes Federation - IDF, cerca de 382 milhões de pessoas são diabéticas e esse número tende a aumentar para além de 592 milhões em menos de 25 anos. Para melhor compreensão do Diabetes mellitus e suas complicações torna-se necessário buscar novos marcadores para a doença. O DM promove estresse oxidativo, inflamação e a formação de produtos avançados de glicação não enzimática (AGES), o que leva a dano tecidual no paciente diabético. Marcadores de dano oxidativo em proteínas e lipídeos na vigência do DM têm sido amplamente abordados na literatura, no entanto o estudo de lesões em DNA ainda requer mais atenção em modelos in vivo. Este trabalho teve como objetivo avaliar o dano oxidativo e resultante de glicação avançada em rim, fígado, cerebelo, sangue e urina de animais diabéticos, assim como a modulação do dano por diferentes períodos de tratamento com insulina, a fim de verificar se o controle da glicemia nos animais diabéticos protege contra a indução dos danos em biomoléculas. Para a indução do DM nos ratos Sprague-Dawley foram administrados 40 mg de STZ por kg de peso corpóreo por via intravenosa. Os níveis de MDA e 5-metildC foram avaliados por HPLC-DAD. A quantificação de HbA1c e dos adutos 1,N2-εdGuo, 1,N6-εdAdo, 8-oxodG e CEdG foi realizada por sistema HPLC-ESI-MS/MS. Os níveis de nitrito sérico foram determinados por leitura da absorbância em espectrofotômetro e a concentração de creatinina plasmática foi determinada por analisador bioquímico. Os resultados mostraram que as alterações metabólicas desencadeadas pela condição de hiperglicemia persistente não são prontamente revertidas após o controle da glicemia. Os níveis glicêmicos e de HbA1c apresentam diferença significativa entre os grupos de animais hiperglicêmicos e sadios, sendo observada uma queda dos valores de HbA1c somente a partir do tratamento com insulina por 6 semanas. Em plasma, rim e fígado as concentrações de MDA seguem o perfil de concentração de hemoglobina glicada (HbA1c), indicando que os eventos de glicação e estresse oxidativo podem estar relacionados. O controle glicêmico também apresentou efeito benéfico para a excreção de CEdG e 1,N6-εdAdo em urina, apesar de ser observado a partir dos níveis de 8- oxodG que a hiperinsulinemia leva a um quadro de estresse oxidativo. As três lesões são geradas por vias distintas: glicação avançada, peroxidação lipídica e ROS. Portanto, além do controle glicêmico, é importante que se desenvolvam estratégias de intervenção nas vias bioquímicas alteradas pela condição de hiperglicemia, a fim de reduzir os riscos das complicações decorrentes do diabetes mellitus. / Diabetes mellitus is generally considered one of the most challenging health problems of the 21st century. According to recent estimates from the International Diabetes Federation - IDF, about 382 million people have diabetes and this number is expected to increase beyond 592 million in less than 25 years. For a better understanding of diabetes mellitus and its complications becomes necessary to search for new biomarkers for the disease. The DM promotes oxidative stress, inflammation and the formation of advanced glycation end products (AGEs), which leads to tissue damage in the diabetic patient. Markers of oxidative damage to proteins and lipids in the presence of DM have been widely discussed in literature, however the study of DNA lesions in vivo models still requires more attention. This study aimed to evaluate the oxidative damage and advanced glycation in the kidney, liver, cerebellum, blood and urine of diabetic animals, as well as damage modulation for different periods of insulin treatment in order to verify that the glycaemic control in diabetic animals protects against induction of biomolecules damage. For induction of diabetes in Sprague-Dawley rats were administered 40 mg STZ per kg body weight intravenously. MDA and 5-metildC were evaluated by HPLC-DAD. The quantification of HbA1c and adducts 1,N2-εdGuo, 1,N6-εdAdo, 8-oxodG and CEdG was performed by HPLC-ESI-MS / MS system. The serum nitrite was determined by reading the absorbance in a spectrophotometer and the plasma creatinine concentration was determined by biochemical analyzer. The results showed that metabolic changes triggered by the condition of persistent hyperglycemia are not readily reversed after glycemic control. Blood glucose and HbA1c levels are significantly different between the groups of hyperglycemic and healthy animals, and was observed a fall in HbA1c only from insulin treatment for 6 weeks. In plasma, kidney and liver concentrations follow the profile of MDA concentration of glycated hemoglobin (HbA1c), indicating that the events of glycation and oxidative stress may be related. Glycemic control also showed beneficial effect for urine excretion of CEdG and 1,N6-εdAdo despite could be seen from 8-oxodG levels that the hyperinsulinaemia leads to a frame of oxidative stress. The three lesions are generated by distinct pathways: advanced glycation, lipid peroxidation and ROS. Therefore, beyond glycaemic control, it is important to develop intervention strategies in biochemical pathways altered by the condition of hyperglycemia in order to reduce the complications risk of diabetes mellitus.

A Neuropatia autonômica cardiovascular (NAC), apesar de ter sido apontada como fator de risco independente para doença cardiovascular (DCV) em pacientes com diabetes tipo 1 (DM1), permanece subdiagnosticada. Os objetivos do trababalho foram determinar a prevalência de NAC e seus indicadores clínicos e laboratoriais em pacientes com DM1 e a associação com outras complicações crônicas do diabetes, além de avaliar a concordância entre os critérios diagnósticos da NAC determinados pelos parâmetros da análise espectral e pelos testes reflexos cardiovasculares. Pacientes com DM1, duração da doença ≥ 5 anos e com idade ≥ 13 anos foram submetidos a um questionário clínico-epidemiológico, a coleta de sangue e de urina para determinação da concentração urinária de albumina, ao mapeamento de retina, e exame clínico para pesquisa de neuropatia diabética sensitivo motora além da realização de testes reflexos cardiovasculares. Cento e cinquenta e um pacientes com DM1, 53.6 % do sexo feminino, 45.7% brancos, com média de idade de 33.4 13 anos, idade ao diagnóstico de 17.2 9.8 anos, duração de DM1 de 16.3 9.5 anos, índice de massa corporal (IMC) de 23.4 (13.7-37.9) Kg/m2 e níveis de hemoglobina glicada de 9.1 2% foram avaliados. Após realização dos testes para rastreamento das complicações microvasculares, encontramos neuropatia diabética sensitivo motora, retinopatia diabética, nefropatia diabética e NAC em 44 (29.1%), 54 (38%), 35 (24.1%) e 46 (30.5%) dos pacientes avaliados, respectivamente. A presença de NAC foi associada com idade (p=0.01), duração do DM (p=0.036), HAS (p=0.001), frequência cardíaca em repouso (p=0.000), HbA1c (p=0.048), uréia (p=0.000), creatinina (p=0.008), taxa de filtração glomerular (p=0.000), concentração urinária de albumina (p=0.000), níveis séricos de LDL-colesterol (p=0.048), T4 livre (p=0.023) e hemoglobina (p=0.01) e a presença de retinopatia (p=0.000), nefropatia (p=0.000) e neuropatia diabética sensitivo motora (p=0.000), além dos seguintes sintomas; lipotimia (p=0.000), náuseas pós alimentares (p=0.042), saciedade precoce (p=0.031), disfunção sexual (p=0.049) e sudorese gustatória (p=0.018). No modelo de regressão logística binária, avaliando o diagnóstico de NAC como variável dependente, foi observado que apenas a FC em repouso, presença de neuropatia diabética sensitivo motora e retinopatia diabética foram consideradas variáveis independentes significativamente. A NAC é uma complicação crônica comum do DM1, atingindo cerca de 30% dos pacientes estudados e encontra-se associada à presença de outras complicações da doença. Indicadores da presença de NAC nos pacientes avaliados incluíram a idade, duração do diabetes, presença de HAS, frequência cardíaca de repouso e presença de sintomas sugestivos de neuropatia autonômica. O presente estudo ratifica a importância do rastreamento sistemático e precoce desta complicação. / The cardiovascular autonomic neuropathy (CAN), although considered as an independent risk factor for cardiovascular disease (CVD) in both patients with type 1 diabetes (T1D), remains underdiagnosed. The objective were to determine the prevalence, clinical and laboratorial indicators of CAN in patients with T1D and its association with other chronic complications of diabetes and evaluate the concordance between the diagnostic criteria for CAN diagnosis determined by the parameters of spectral analysis and the cardiovascular reflex tests. Patients with T1D aged ≥ 13 years and diabetes duration ≥ 5 years underwent a clinical-epidemiological survey, had blood samples collected, urinary samples for the determination of urinary albumin concentration, ophtalmoscopic exam, clinical neurological examination for diabetic neuropathy screeening and cardiovascular reflex tests. One hundred and fifty one patients with T1D, 53.6 % female, 45.7% Caucasian, mean age of 33.4 13 years, age at diagnosis of 17.2 9.8 years, diabetes duration of 16.3 9.5 years, body mass index (BMI) of 23.4 (13.7-37.9) kg/m2, glycated hemoglonin levels of 9.1 2% were evaluated. After performing the tests for screening for microvascular complications, we found diabetic sensory motor neuropathy, diabetic retinopathy, diabetic nephropathy and CAN in 44 (29.1%), 54 (38%), 35 (24.1%) and 46 (30.5%) of the patients, respectively. CAN was associated with age (p=0.01), diabetes duration (p=0.036), hypertension (p=0.001), resting heart rate (p=0.000), HbA1c (p=0.048), urea (p=0.000), creatinine (p=0.008), glomerular filtration rate (p=0.000), urinary albumin concentration (p=0.000), LDL-cholesterol (p=0.048), free T4 (p=0.023), hemoglobin (p=0.01) and presence of retinopathy (p=0.000), nephropathy (p=0.000) and diabetic neuropathy (p=0.000), the following symptons syncope (p=0.000), post prandial nausea (p=0.042), early saciety (p=0.031), sexual dysfunction (p=0.049) and gustatory sweating (p=0.018). In binary logistic regression model evaluating the diagnosis of CAN as a dependent variable, it was observed that only resting heart rate, presence of diabetic neuropathy and retinopathy were considered independent variables significantly. CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications of T1D. Indicators of the presence of CAN included age, duration of diabetes, presence of hypertension, resting heart rate and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for this complication.

A Neuropatia autonômica cardiovascular (NAC), apesar de ter sido apontada como fator de risco independente para doença cardiovascular (DCV) em pacientes com diabetes tipo 1 (DM1), permanece subdiagnosticada. Os objetivos do trababalho foram determinar a prevalência de NAC e seus indicadores clínicos e laboratoriais em pacientes com DM1 e a associação com outras complicações crônicas do diabetes, além de avaliar a concordância entre os critérios diagnósticos da NAC determinados pelos parâmetros da análise espectral e pelos testes reflexos cardiovasculares. Pacientes com DM1, duração da doença ≥ 5 anos e com idade ≥ 13 anos foram submetidos a um questionário clínico-epidemiológico, a coleta de sangue e de urina para determinação da concentração urinária de albumina, ao mapeamento de retina, e exame clínico para pesquisa de neuropatia diabética sensitivo motora além da realização de testes reflexos cardiovasculares. Cento e cinquenta e um pacientes com DM1, 53.6 % do sexo feminino, 45.7% brancos, com média de idade de 33.4 13 anos, idade ao diagnóstico de 17.2 9.8 anos, duração de DM1 de 16.3 9.5 anos, índice de massa corporal (IMC) de 23.4 (13.7-37.9) Kg/m2 e níveis de hemoglobina glicada de 9.1 2% foram avaliados. Após realização dos testes para rastreamento das complicações microvasculares, encontramos neuropatia diabética sensitivo motora, retinopatia diabética, nefropatia diabética e NAC em 44 (29.1%), 54 (38%), 35 (24.1%) e 46 (30.5%) dos pacientes avaliados, respectivamente. A presença de NAC foi associada com idade (p=0.01), duração do DM (p=0.036), HAS (p=0.001), frequência cardíaca em repouso (p=0.000), HbA1c (p=0.048), uréia (p=0.000), creatinina (p=0.008), taxa de filtração glomerular (p=0.000), concentração urinária de albumina (p=0.000), níveis séricos de LDL-colesterol (p=0.048), T4 livre (p=0.023) e hemoglobina (p=0.01) e a presença de retinopatia (p=0.000), nefropatia (p=0.000) e neuropatia diabética sensitivo motora (p=0.000), além dos seguintes sintomas; lipotimia (p=0.000), náuseas pós alimentares (p=0.042), saciedade precoce (p=0.031), disfunção sexual (p=0.049) e sudorese gustatória (p=0.018). No modelo de regressão logística binária, avaliando o diagnóstico de NAC como variável dependente, foi observado que apenas a FC em repouso, presença de neuropatia diabética sensitivo motora e retinopatia diabética foram consideradas variáveis independentes significativamente. A NAC é uma complicação crônica comum do DM1, atingindo cerca de 30% dos pacientes estudados e encontra-se associada à presença de outras complicações da doença. Indicadores da presença de NAC nos pacientes avaliados incluíram a idade, duração do diabetes, presença de HAS, frequência cardíaca de repouso e presença de sintomas sugestivos de neuropatia autonômica. O presente estudo ratifica a importância do rastreamento sistemático e precoce desta complicação. / The cardiovascular autonomic neuropathy (CAN), although considered as an independent risk factor for cardiovascular disease (CVD) in both patients with type 1 diabetes (T1D), remains underdiagnosed. The objective were to determine the prevalence, clinical and laboratorial indicators of CAN in patients with T1D and its association with other chronic complications of diabetes and evaluate the concordance between the diagnostic criteria for CAN diagnosis determined by the parameters of spectral analysis and the cardiovascular reflex tests. Patients with T1D aged ≥ 13 years and diabetes duration ≥ 5 years underwent a clinical-epidemiological survey, had blood samples collected, urinary samples for the determination of urinary albumin concentration, ophtalmoscopic exam, clinical neurological examination for diabetic neuropathy screeening and cardiovascular reflex tests. One hundred and fifty one patients with T1D, 53.6 % female, 45.7% Caucasian, mean age of 33.4 13 years, age at diagnosis of 17.2 9.8 years, diabetes duration of 16.3 9.5 years, body mass index (BMI) of 23.4 (13.7-37.9) kg/m2, glycated hemoglonin levels of 9.1 2% were evaluated. After performing the tests for screening for microvascular complications, we found diabetic sensory motor neuropathy, diabetic retinopathy, diabetic nephropathy and CAN in 44 (29.1%), 54 (38%), 35 (24.1%) and 46 (30.5%) of the patients, respectively. CAN was associated with age (p=0.01), diabetes duration (p=0.036), hypertension (p=0.001), resting heart rate (p=0.000), HbA1c (p=0.048), urea (p=0.000), creatinine (p=0.008), glomerular filtration rate (p=0.000), urinary albumin concentration (p=0.000), LDL-cholesterol (p=0.048), free T4 (p=0.023), hemoglobin (p=0.01) and presence of retinopathy (p=0.000), nephropathy (p=0.000) and diabetic neuropathy (p=0.000), the following symptons syncope (p=0.000), post prandial nausea (p=0.042), early saciety (p=0.031), sexual dysfunction (p=0.049) and gustatory sweating (p=0.018). In binary logistic regression model evaluating the diagnosis of CAN as a dependent variable, it was observed that only resting heart rate, presence of diabetic neuropathy and retinopathy were considered independent variables significantly. CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications of T1D. Indicators of the presence of CAN included age, duration of diabetes, presence of hypertension, resting heart rate and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for this complication.

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O sistema renina-angiotensina e o estresse oxidativo têm participação importante na fisiopatologia das complicações crônicas do diabetes. No presente estudo, foram avaliados 103 pacientes com diabetes tipo 1 (DM1) com idade de 28,810,6 anos e duração de doença de 13,18,5 anos e 158 controles não diabéticos quanto à presença dos polimorfismos I/D da ECA e C242T do p22phox, componente essencial para a ativação da NADPH oxidase. Esta análise foi realizada por reação de polimerase em cadeia para ambos os polimorfismos, seguida de restrição enzimática para avaliação do polimorfismo C242T p22phox. Ambas as distribuições genotípicas obedeciam ao princípio do equilíbrio de Hardy-Weinberg. Os pacientes diabéticos foram submetidos a avaliação clínica e laboratorial quanto à presença de fatores associados ao risco de complicações (história de tabagismo e antecedentes familiares de diabetes tipo 2, dose diária de insulina, níveis pressóricos, índice de massa corporal, relação cintura-quadril, excreção urinária de albumina, taxa de filtração glomerular, perfil lipídico, controle glicêmico, níveis de proteína C-reativa) e rastreados quanto à presença de nefropatia diabética, considerada presença de micro ou macroalbuminúria; retinopatia diabética não proliferativa ou proliferativa e hipertensão arterial. Não houve diferença significativa entre a presença dos alelos D e I da ECA ou C e T do p22phox entre diabéticos e controles. Os polimorfismos avaliados não apresentaram associação com a presença de nefropatia, retinopatia ou hipertensão arterial. Pacientes portadores do alelo D apresentaram maiores níveis de pressão arterial diastólica (72,2 12,3 vs 65,4 11,6 mmHg , p=0,047) e proteína C-reativa comparados aos portadores do genótipo II [0,18 (0,04-0,38) vs 0,09 (0,04-0,16) mg/dl, p=0,05] , porém ambas as análises perderam significância estatística após correção para duração do diabetes. A combinação dos polimorfismos não esteve associada à presença de complicações microvasculares ou hipertensão arterial. Concluímos que, na população de diabéticos tipo 1 estudada, a frequência dos polimorfismos I/D da ECA e C242T do p22phox , isoladamente ou em combinação, não apresentou diferença em pacientes com ou sem complicações microvasculares precoces ou hipertensão arterial. Os níveis dos diferentes marcadores de risco cardiovascular também não apresentaram diferença nos pacientes com os polimorfismos acima descritos. Entretanto, estudos prospectivos poderão determinar a possível interação entre estes polimorfismos e a duração do diabetes na expressão clínica das complicações crônicas da doença. / The renin-angiotensin system and the oxidative stress play an important role in the pathogenesis of the diabetic complications.In the present study 103 patients with type 1 diabetes (T1DM) aged 28.8 10.6 years and with a disease duration of 13.1 8.5 years and 158 non-diabetic controls were evaluated for the presence of the I / D polymorphism of the angiotensin converting enzyme (ACE) and the C242T polymorphism of the p22phox, an essential component for NADPH oxidase activation. The analysis was performed using polymerase chain reaction for both polymorphisms, followed by enzymatic restriction for C242T p22phox polymorphism. Genotypic distributions of both polymorphisms were in Hardy-Weinberg equilibrium. Diabetic patients underwent clinical and laboratory evaluation for the presence of risk factors associated with complications of diabetes (smoking and family history of type 2 diabetes, daily insulin dose, blood pressure, body mass index, waist hip ratio, urinary albumin excretion, glomerular filtration rate, lipid profile, glycemic control, C-reactive protein levels) and screened for the presence of diabetic nephropathy, considered as the presence of micro or macroalbuminuria, diabetic retinopathy and hypertension. There was no significant difference between the presence of ACE D or I allele and p22phox C or T allele between diabetic patients and controls. The evaluated polymorphisms were not associated with the presence of nephropathy, retinopathy or hypertension. Patients with the D allele showed higher levels of diastolic blood pressure (72.2 12.3 vs 65.4 11.6 mmHg, p = 0.047) and C-reactive protein compared with those carrying the II genotype [0.18 (0.04-0.38) vs 0.09 (0.04-0.16) mg/dl, p = 0.05], but both analysis lost statistical significance after correction for duration of diabetes. The combination of both polymorphisms was not associated with microvascular complications or hypertension. We conclude that in the studied population of type 1 diabetic patients, the frequency of ACE I / D and C242T of p22phox polymorphisms, alone or in combination, was not different in patients with or without early microvascular complications or hypertension. Also, the levels of different markers of cardiovascular risk did not differ for patients with the polymorphisms described above. However, prospective studies may determine the possible interaction between these polymorphisms and duration of diabetes in the clinical expression of chronic complications of diabetes.