The aim was to determine whether the dietary glycemic index (GI) related to coronary heart disease (CHD) risk and whether oxidized LDL could explain this relation. Nine prospective cohorts of GI or glycemic load (GL) associations were pooled in a meta-analysis and showed an increased risk of CHD for high GI (near significant at RR=1.13, 95%CI; 1.00-1.26) and GL diets (significant at RR=1.40, 95%CI; 1.17-1.68), both with significant evidence of heterogeneity (P<0.07). Sera from 151 type 2 diabetics who completed a 6-month trial of a low GI diet demonstrated no treatment difference in measures of oxidative damage. However, when data from both treatments were pooled, oxidized LDL as a marker of CHD risk inversely related to low GI carbohydrate intake. We conclude that GI and GL relate to CHD and oxidative damage to LDL may explain part of this association.

Individuals with abdominal obesity are at higher risk for developing type 2 diabetes, predisposing cardiovascular events and insulin resistance. Low glycemic index (GI) diets may be beneficial in the management of insulin resistance. Insulin resistance is associated with increased intramyocellular lipid (IMCL) content as measured by proton nuclear magnetic resonance spectroscopy (1H-MRS). The primary objective of this thesis was to determine whether a low GI diet can improve insulin sensitivity by reducing IMCL of skeletal muscle. One hundred and twenty-one male and female participants aged 30 to 70 years (mean+SD, 53+10)) with abdominal obesity, entered a 4 to 6 week weight-maintaining, low-fat dietary advice run-in phase. Of the 121 eligible participants, 95 completed the run-in phase and were randomly assigned to either a low-GI (LGID, n=48) or high-GI diet (HGID, n=47) for 24 weeks. Participants underwent a 75g oral glucose tolerance test (OGTT) and had soleus-muscle IMCL measured by 1H-MRS at the beginning and end of the intervention period. Insulin sensitivity was assessed by the homeostatic model assessment index (HOMA) and the insulinogenic index (ISI) was calculated for insulin secretion. At the end of the run-in phase, there were significant reductions in serum total-, LDL-, and HDL-cholesterol (all, p<0.0001) and an increase in fasting plasma glucose (p<0.05). In 57 participants who wore a continuous glucose monitoring system for 24 hours during the run-in period, a total of 30% (p<0.001) of the variation in the incremental area under the blood glucose curve after self-selected breakfast meals was explained by GI. After 24 weeks, diet GI was significantly lower in the LGID than HGID group (55.5+3.1 vs 63.9+3.1, p<0.0001). Plasma glucose 60 minutes after the OGTT was significantly lower on the LGID than at baseline (p<0.05) and there was a non-significant trend towards an increase in ISI (p=0.07). On the HGID, ISI increased significantly from baseline (p<0.01). It is concluded that the LGID reduced 60 minute plasma glucose but did not significantly affect IMCL or insulin sensitivity in individuals with abdominal obesity.

Individuals with abdominal obesity are at higher risk for developing type 2 diabetes, predisposing cardiovascular events and insulin resistance. Low glycemic index (GI) diets may be beneficial in the management of insulin resistance. Insulin resistance is associated with increased intramyocellular lipid (IMCL) content as measured by proton nuclear magnetic resonance spectroscopy (1H-MRS). The primary objective of this thesis was to determine whether a low GI diet can improve insulin sensitivity by reducing IMCL of skeletal muscle. One hundred and twenty-one male and female participants aged 30 to 70 years (mean+SD, 53+10)) with abdominal obesity, entered a 4 to 6 week weight-maintaining, low-fat dietary advice run-in phase. Of the 121 eligible participants, 95 completed the run-in phase and were randomly assigned to either a low-GI (LGID, n=48) or high-GI diet (HGID, n=47) for 24 weeks. Participants underwent a 75g oral glucose tolerance test (OGTT) and had soleus-muscle IMCL measured by 1H-MRS at the beginning and end of the intervention period. Insulin sensitivity was assessed by the homeostatic model assessment index (HOMA) and the insulinogenic index (ISI) was calculated for insulin secretion. At the end of the run-in phase, there were significant reductions in serum total-, LDL-, and HDL-cholesterol (all, p<0.0001) and an increase in fasting plasma glucose (p<0.05). In 57 participants who wore a continuous glucose monitoring system for 24 hours during the run-in period, a total of 30% (p<0.001) of the variation in the incremental area under the blood glucose curve after self-selected breakfast meals was explained by GI. After 24 weeks, diet GI was significantly lower in the LGID than HGID group (55.5+3.1 vs 63.9+3.1, p<0.0001). Plasma glucose 60 minutes after the OGTT was significantly lower on the LGID than at baseline (p<0.05) and there was a non-significant trend towards an increase in ISI (p=0.07). On the HGID, ISI increased significantly from baseline (p<0.01). It is concluded that the LGID reduced 60 minute plasma glucose but did not significantly affect IMCL or insulin sensitivity in individuals with abdominal obesity.

Hyperglycemia is prevalent in critical care, as patients experience stress-induced hyperglycemia, even with no history of diabetes. Hyperglycemia has a significant impact on patient mortality, outcome and health care cost. Tight regulation can significantly reduce these negative outcomes, but achieving it remains clinically elusive, particularly with regard to what constitutes tight control and what protocols are optimal in terms of results and clinical effort. Hyperglycemia in critical care is not largely benign, as once thought, and has a deleterious effect on outcome. Recent studies have shown that tight glucose regulation to average levels from 6.1–7.75 mmol/L can reduce mortality 17–45%, while also significantly reducing other negative clinical outcomes. However, clinical results are highly variable and there is little agreement on what levels of performance can be achieved and how to achieve them. A typical clinical solution is to use ad-hoc protocols based primarily on experience, where large amounts of insulin, up to 50 U/hr, are titrated against glucose measurements variably taken every 1–4 hours. When combined with the unpredictable and sudden metabolic changes that characterise this aspect of critical illness and/or clinical changes in nutritional support, this approach results in highly variable blood glucose levels. The overall result is sustained periods of hyper- or hypo- glycemia, characterised by oscillations between these states, which can adversely affect clinical outcomes and mortality. The situation is exacerbated by exogenous nutritional support regimes with high dextrose content. Model-based predictive control can deliver patient specific and adaptive control, ideal for such a highly dynamic problem. A simple, effective physiological model is presented in this thesis, focusing strongly on clinical control feasibility. This model has three compartments for glucose utilisation, interstitial insulin and its transport, and insulin kinetics in blood plasma. There are two patient specific parameters, the endogenous glucose removal and insulin sensitivity. A novel integral-based parameter identification enables fast and accurate real-time model adaptation to individual patients and patient condition. Three stages of control algorithm developments were trialed clinically in the Christchurch Hospital Department of Intensive Care Medicine. These control protocols are adaptive and patient specific. It is found that glycemic control utilising both insulin and nutrition interventions is most effective. The third stage of protocol development, SPRINT, achieved 61% of patient blood glucose measurements within the 4–6.1 mmol/L desirable glycemic control range in 165 patients. In addition, 89% were within the 4–7.75 mmol/L clinical acceptable range. These values are percentages of the total number of measurements, of which 47% are two-hourly, and the rest are hourly. These results showed unprecedented tight glycemic control in the critical care, but still struggle with patient variability and dynamics. Two stochastic models of insulin sensitivity for the critically ill population are derived and presented in this thesis. These models reveal the highly dynamic variation in insulin sensitivity under critical illness. The stochastic models can deliver probability intervals to support clinical control interventions. Hypoglycemia can thus be further avoided with the probability interval guided intervention assessments. This stochastic approach brings glycemic control to a more knowledge and intelligible level. In “virtual patient” simulation studies, 72% of glycemic levels were within the 4–6.1 mmol/L desirable glycemic control range. The incidence level of hypoglycemia was reduced to practically zero. These results suggest the clinical advances the stochastic model can bring. In addition, the stochastic models reflect the critical patients’ insulin sensitivity driven dynamics. Consequently, the models can create virtual patients to simulated clinical conditions. Thus, protocol developments can be optimised with guaranteed patient safety. Finally, the work presented in this thesis can act as a starting point for many other glycemic control problems in other environments. These areas include the cardiac critical care and neonatal critical care that share the most similarities to the environment studied in this thesis, to general diabetes where the population is growing exponentially world wide. Furthermore, the same pharmacodynamic modelling and control concept can be applied to other human pharmacodynamic control problems. In particular, stochastic modelling can bring added knowledge to these control systems. Eventually, this added knowledge can lead clinical developments from protocol simulations to better clinical decision making.

This dissertation examines the impact of exercise rehabilitation and the components of exercise prescriptions on optimizing health outcomes for people with diabetes (DM). Exercise is an accepted part of the diabetes management regime to help prevent or slow the progression of the disease. A combined aerobic and resistance training protocol is the recommended exercise regime for people with DM, but the question remains as to what the optimal dose may be for glycemic control and reduction of cardiovascular risk. This thesis aims to address three objectives surrounding optimal exercise prescriptions for diabetes: 1) To investigate aerobic exercise prescription efficacy in people with DM, coronary artery disease (CAD) and both CAD and DM to determine if there are population-specific VO2peak responses to exercise prescription; 2) To determine the optimal volume and intensity of resistance training exercise, in combination with aerobic training, that may improve glucose control, cardiovascular risk factors and body composition in people with type 2 DM (T2DM); and 3) To study the relationship between exercise performance, physiological changes and depressive mood in people with T2DM participating in a supervised, exercise program. Encouraging participation in an appropriately prescribed aerobic and resistance training program may help to improve adherence to exercise and elicit optimal health outcomes in people with T2DM. Tailoring the exercise prescription to suit the patient’s lifestyle, history and capacity is the utmost challenge for health care providers who hope to provide a complementary, non-pharmacologic therapeutic option for their patients.

abstract: This study examined the effect of consuming pinto, black, and dark red kidney beans with white rice in comparison to a white rice only control meal on the glycemic response of adults with type 2 diabetes (T2D). These bean and rice combinations are part of many traditional diets. Seventeen subjects with T2D treated by diet and/or metformin were randomly assigned to 4 treatments: white rice (control), pinto beans/rice, black beans/rice, and dark red kidney beans/rice. All treatments were portioned by weight and matched for available carbohydrate content of &sim; 50 grams. Capillary whole blood samples were collected at baseline and at 30, 60, 90, 120, 150 and 180 minutes posttreatment and assessed for glucose concentration using the YSI Stat Plus Analyzer. Net change glucose responses were significantly lower for the pinto, black, and dark red kidney bean and rice meals than control at 90, 120 and 150 minutes posttreatment (P < 0.05). Incremental area under the curve (iAUC) values were also significantly reduced for the bean/rice meals containing pinto (P < 0.01) and black beans (P < 0.05) in contrast to the rice control. Results suggest that the combination of whole beans and rice may be beneficial to those with T2D to assist with blood glucose management. / Dissertation/Thesis / M.S. Nutrition 2011

Diabetes Mellitus (DM) and periodontal disease (PD) are both common, chronic and debilitating diseases. This paper will illustrate the bidirectional relationship between the two disease processes and how treatment of periodontal disease can improve the glycemic control and overall health of patients with DM. Multiple studies that will be discussed have shown this relationship and concluded PD treatment improves the health of patients with DM, especially in regards to glycemic control. Unfortunately, at this time there is very little data from large scale studies on this topic. The proposed study intends to perform a RCT to show that non-surgical PD treatment in patients with periodontal disease improves glycemic control, hsCRP levels, and kidney function of patients with diabetes mellitus. The significance of this study cannot be understated. The hypothesized conclusions would provide an adjunct therapy to treat DM and its complications potentially preventing end organ damage and progression of disease, which would help to improve the great healthcare burden of this disease.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-09-04T19:21:42Z No. of bitstreams: 1 Zaira Onofre Nunes Avaliação do controle glicêmico e seus determinantes em pacientes com diabetes mellitus....pdf: 1394652 bytes, checksum: 56dba13366982abd621882b5e8bfad9c (MD5) / Made available in DSpace on 2012-09-04T19:21:42Z (GMT). No. of bitstreams: 1 Zaira Onofre Nunes Avaliação do controle glicêmico e seus determinantes em pacientes com diabetes mellitus....pdf: 1394652 bytes, checksum: 56dba13366982abd621882b5e8bfad9c (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / O Diabetes Mellitus (DM) é uma doença metabólica crônica caracterizada por hiperglicemia persistente devido a deficiência na secreção e/ou na ação da insulina. Geralmente, está associada a complicações micro e macrovasculares devido a persistência de valores altos de glicemia. Por conta da maior industrialização, mudança na qualidade e nos hábitos de vida, maus hábitos alimentares, maior expectativa de vida, dentre outros, o DM vem atingindo proporções epidêmicas no mundo. Este crescimento atinge tanto países desenvolvidos quanto em desenvolvimento constituindo, assim, um problema de saúde pública. Os dados sobre a epidemiologia do diabetes na Venezuela são escassos e limitados. Estima-se que a prevalência de DM neste país varie de 3.8 a 7.3% e acredita-se estar em crescimento. Informações sobre o controle glicêmico e fatores de risco para o controle inadequado do diabetes são importantes para o planejamento de programas de saúde que contribuam na melhoria do atendimento ao paciente diabético. Este trabalho teve como objetivo estimar a prevalência de controle glicêmico inadequado em pacientes diabéticos de acordo com o tipo e duração da doença, determinar fatores associados ao mau controle glicêmico e identificar informações úteis para programas de melhoria do controle glicêmico em pacientes com diabetes. Este estudo é um inquérito de corte-transversal, conduzido de janeiro a junho de 2007, onde a população em estudo foi composta por pacientes diabéticos atendidos regularmente em serviços e centros médicos em oito regiões da Venezuela. O controle glicêmico foi avaliado através da dosagem de HbA1c pelo método de HPLC (High-Performance Liquid Chromatography). O ponto de corte para determinar controle adequado foi HbA1c <7.0%. No total foram avaliados 4.075 indivíduos, sendo 349 (9%) portadores de DM tipo 1 (DM1) e 3.726 (91%) com DM tipo 2 (DM2). A prevalência de controle glicêmico inadequado foi de 76%; ao estratificarmos por tipo de diabetes, o pacientes com DM1 apresentaram 87% de controle inadequado e aqueles com DM2 75%. Na avaliação da regressão linear, das variáveis analisadas mostraram associação com o pior controle glicêmico para o DM1, o baixo nível de escolaridade e a pior auto-percepção do controle glicêmico. Já para o DM2 mostraram associação com pior controle glicêmico menor idade, tipo de tratamento, menor nível de escolaridade, maior duração da doença, aderência ruim a dieta, a participação em grupos de educação para o diabetes e a pior auto-percepção do controle. Apesar das evidências clinicas que apóiam o controle rigoroso da glicemia, constatamos que poucos pacientes diabéticos na Venezuela alcançaram as metas de controle glicêmico recomendadas. Isso pode contribuir para o aumento das taxas de complicações micro e macrovasculares e podem impactar em aumento nos custos dos cuidados de saúde. / Diabetes Mellitus (DM) is a chronic metabolic disease characterized by persistent hyperglycemia due to deficiency in the secretion and / or insulin action. Generally is associated with macrovascular and microvascular complications due to persistent high levels of blood glucose. Due to the increased industrialization, changes in quality and lifestyle, poor eating habits, higher life expectancy, among others, the DM is reaching epidemic proportions in the world. This increase affects both developed and developing countries and thus constitutes a public health problem. Data on the epidemiology of diabetes in Venezuela is scarce and limited. It is estimated that the prevalence of DM in this country ranges from 3.8 to 7.3% and is believed to be growing. Information on glycemic control and risk factors for inadequate control of diabetes are important for planning health programs that contribute to the improvement of care for diabetic patients. This study aimed to estimate the prevalence of inadequate glycemic control in diabetic patients according to the type and duration of disease, determine factors associated with poor glycemic control and to identify useful information for programs to improve glycemic control in patients with diabetes. This study is a cross-sectional survey, conducted from January to June 2007, which the study population was composed of diabetic patients seen regularly at services and medical centers in eight regions of Venezuela. Glycemic control was assessed by measurement of HbA1c by HPLC (High-Performance Liquid Chromatography). The cutoff point for determining appropriate control was HbA1c <7.0%. Overall 4.075 individuals were evaluated, 349 (9%) patients with type 1 DM (T1DM) and 3.726 (91%) with type 2 DM (T2DM). The prevalence of poor glycemic control was 76%; when stratified by type of diabetes, patients with T1DM were 87% of inadequately controlled and those with T2DM 75%. In the evaluation of linear regression, the variables showed association with poor glycemic control for type 1 diabetes, the low level of education and worse self-perception of glycemic control. As for DM2 were associated with poor glycemic control variables younger age, type of treatment, lower education level, longer disease duration, poor adherence to diet, group education for diabetes and worse self-perception of control. Despite the clinical evidence supporting tight control of diabetes, we found that few diabetic patients in Venezuela met the recommended glycemic control targets. This may contribute to increased rates of macrovascular and microvascular complications and which may impact on rising costs of health care.

O Diabetes Mellitus (DM) é uma doença metabólica que implica em altas incidências de mortalidade e morbidade. A hiperglicemia crônica é responsável pelo surgimento de inúmeras complicações em longo prazo nestes pacientes. Atualmente, é recomendado por diretrizes internacionais que pacientes com DM sejam monitorados e manejados em seu tratamento a partir dos níveis de hemoglobina glicada (A1C). A A1C é formada por reações não enzimáticas de glicação na hemoglobina, refletindo a glicemia dos últimos 120 dias. A A1C possui forte associação com os desfechos clínicos no DM e apresenta uma excelente padronização de seus métodos analíticos. Contudo, diversas situações clínicas podem interferir falsamente em seus níveis e prejudicar a interpretação de seus resultados, como em anemias (carenciais ou hemolíticas), hemoglobinopatias, gravidez, doença renal crônica, etc. Por outro lado, a albumina glicada (AG) é uma frutosamina formada por glicações na albumina e reflete uma glicemia média de cerca de 2 a 3 semanas. A AG não é influenciada pela concentração de outras proteínas no plasma e também não sofre interferência pelas condições que afetam a A1C. Este marcador tem sido fortemente avaliado como uma ferramenta alternativa para a A1C, a partir da análise de seus níveis por um novo método enzimático descrito em 2002. Estudos tem demonstrado uma forte associação entre estes dois marcadores e grande semelhança em predizer as complicações do DM. Entretanto, a AG se mostra melhor para avaliar flutuações nos níveis de glicose e a resposta ao tratamento terapêutico. Neste trabalho, foi avaliado o desempenho analítico de dois kits enzimáticos de AG e realizado uma comparação entre os métodos, encontrando excelentes resultados. Ainda, foi determinado o intervalo de referência para os níveis de AG em brasileiros saudáveis. A forte correlação encontrada entre AG e A1C demonstra que a AG pode ser um teste útil para o controle glicêmico no DM, principalmente quando a A1C não é recomendada. / Diabetes Mellitus is a metabolic disease with high incidence rates of mortality and morbidity. Chronic hyperglycemia is responsible for several long-term complications in these patients. Currently, international guidelines recommend that glycemic monitoring in DM should be performed by glycated hemoglobin (A1C) levels, to provide a correct clinical conduction. A1C is relative to non-enzymatic glycation reactions in hemoglobin and reflects the glucose levels from the last 120 days. It is well established the great association between A1C and clinical outcomes in DM, besides, its analytical methods present an excellent standardization. However, some conditions may influence and imply misinterpretation in A1C results, such as anemia, hemoglobinophaties, pregnancy, chronic renal disease, etc. On the other hand, glycated albumin (GA) is a fructosamine produced by glycation reactions in albumin and it reflects a mean glycemia at around 2 to 3 weeks. GA is not influenced by the concentrations of other plasma proteins, as well as by those conditions that interfere in A1C. GA has been strongly evaluated as an alternative marker to A1C, through its quantitative measurement by an enzymatic methodology described in 2002. Recent studies have demonstrated a high association between GA and A1C and a great similarity between these tests in predicting DM future complications. Nevertheless, GA has showed be better to assess the glucose fluctuations in blood and the response to treatment. This study evaluated the analytical performance of two GA enzymatic kits and also executed a methods comparison, and found excellent results. Also, we established the reference range for GA levels in healthy Brazilians. The high correlation found between GA and A1C indicates that GA could be a useful test for glycemic control in DM, especially when A1C is unreliable.

Orientador: Chung Man Chin / Banca: Antonio de Padua Pithon Cyrino / Banca: Roberto Barbosa Bazotte / Banca: Julieta Ueta / Banca: Rosangela Gonçalves Peccinini / Resumo: No Brasil estima-se a existência de aproximadamente 12 milhões de adultos com Diabetes Mellitus (DM) e destes entre 54 a 76% apresentam taxas de mau controle. Esta situação torna o DM um sério problema de saúde pública, devido tanto ao número de pessoas afetadas como aos custos envolvidos no seu controle e no tratamento de suas complicações. A previsão é que em 2030 haverá um crescimento de 67,11% nesta população. Tal situação demonstra a necessidade de melhora urgente no atendimento ou a inserção de novas abordagens de cuidado com evidências científicas (estudos translacionais). Neste sentido, este estudo translacional fase 1 pretende desenvolver e avaliar um protocolo de Atenção Farmacêutica intensivo com metodologia educacional de empoderamento (ATENFAR-EPW), visando contribuir na melhoria do controle glicêmico e qualidade de vida de adultos com Diabetes Mellitus tipo 2 (DM2). MÉTODOS. Estudo conduzido em 3 etapas por farmacêutico-educador em diabetes: (1) desenvolvimento e elaboração do protocolo de ATENFAR-EPW e de instrumentos para acompanhamento e avaliação de indicadores; (2) estudo clínico controlado e randomizado em dois grupos - grupo de intervenção com n=12 (GAF) e grupo de atendimento usual com n=8 (GAU); (3) avaliação de aceitação do protocolo. RESULTADOS. (1) características do protocolo desenvolvido: (a) atendimento domiciliar e ou... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In Brazil it is estimated there are approximately 12 million adults with Diabetes Mellitus (DM), and, from this population, the rate for poor glycemic control varies from 54 to 76%. This makes DM a serious public health problem due to both, the number of people affected, and the cost of controlling and treating DM related complications. This situation demonstrates the urgent need for improvement in service or the insertion of new approaches to care based on scientific evidence (translational research). Thus, this study aims to develop a translational research and evaluate a protocol for intensive Pharmaceutical Care with educational methodology of empowerment (ATENFAR-EPW), aiming to improve glycemic control and quality of life of adults with diabetes mellitus type 2 (DM2). METHODS. The study was conducted in steps by the pharmacist-educator in diabetes: (1) development and drafting of the protocol ATENFAR-EPW and tools for monitoring and evaluation of the indicators, (2) controlled and randomized clinical study into two groups - the intervention group with n = 12 (GAF) and usual care group with n = 8 (GAU), conducted from October 2010 to July 2011. RESULTS. (1) characteristics of the developed protocol: (a) home care or by phone or outpatient, (b). number of visits / duration = 6 ± 2 visits / 12 weeks, (c) length of service / adult = 56 ± 28 min, (d) no. of interventions / adult = 48 ± 14. (2) Evaluation of the impact of the study: (a) significant reduction in HbA1c (- 1.3 ± 1.1, p = 0.005), (b) significant improvement of... (Complete abstract click electronic access below) / Doutor