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.

Hyperglycaemia is a common condition in the very low birth weight infant and is linked to mortality and increased risks of morbidities such as sepsis and retinopathy of prematurity. The preterm neonate is in a state of transition from complete dependence on the mother to physiological independence. Many metabolic regulation systems are under-developed, attenuating the natural metabolic hormonal control response. Tight regulation of glucose levels can significantly reduce the negative outcomes associated with hyperglycaemia, but achieving it remains clinically elusive for the neonate. Glucose control in adult critical care is a highly researched topic, and several studies have demonstrated significantly improved outcomes with protocols that modulate the insulin and/or nutrition inputs into the patient. Despite the potential, no standard protocol exists for neonates. Glucose restriction is often used as a treatment for neonatal hyperglycaemia, however this deprives the infant of much needed energy for growth. Limited trials of insulin infusions have been reported, based on fixed protocols or ad-hoc clinical decisions that do not objectively account for an individual patient's metabolic state. Model-based methods can deliver control that is patient-specific and adaptive to handle highly dynamic patients. A physiological model of the glucose-insulin regulatory system is presented in this thesis, adapted from adult critical care. This model has three compartments for glucose utilisation, effective interstitial insulin and its transport, and insulin kinetics in blood plasma, with emphasis on clinical applicability. The predictive control for the model is driven by the patient-specific and time-varying insulin sensitivity parameter. A novel integral-based parameter identification enables fast and accurate real-time model adaptation to individual patients and patient condition. Validation on retrospective clinical data demonstrated the model's ability to capture the major dynamics of the glucose-insulin system in the critically ill neonate. Model fit and prediction performance analysis resulted in a similar level of performance as adult intensive care models and thus suitable for model-based targeted control. Comparison of insulin sensitivity profiles with adult critical care patients highlighted the glycaemic control problem as one of managing inter- and intra-patient variability. Stochastic models and time-series methods for forecasting future insulin sensitivity are presented in this thesis. These methods can deliver probability intervals to support clinical control interventions. The risk of adverse glycaemic outcomes given observed variability from cohort-specific and patient-specific forecasting methods can be quantified to inform clinical staff. Hypoglycaemia can thus be further avoided with the probability interval guided intervention assessments. Simulation studies of clinical control trials on `virtual patients' derived from retrospective clinical data provided a framework to optimise control protocol design in-silico. Comparisons with retrospective control showed substantial improvements in glycaemia within the target 4 - 7 mmol/L range by optimising the infusions of insulin. The simulation environment allowed experimentation with controller parameters to arrive at a protocol that operates within the constraints imposed by the clinically fragile state of the preterm infant. The resulting control system was piloted in seven 12-24 hour clinical trials at the Christchurch Women's Neonatal Department. Glucose levels were tightly controlled in all cases over a trial cohort that represented a wide range of patient conditions and severity of illness. Model predictive performance agreed with simulation results and the stochastic model forecast bounds maintained patient safety. Overall, the research presented takes model-based neonatal glycaemic control from concept to proof-of-concept clinical pilot trials. The thesis develops the full range of models, tools and methods to optimise the protocol design and problem solution. This research thus provides a template for model-based glycaemic control development in general that could be extended to other glycaemic control and similar problems.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (M.S.)--University of Wisconsin-Madison, 1993. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 112-126).

The author deals with oxidative stress and its effects on the pathogenesis of various diseases including the development of insulin resistance. The work is divided in the usual way overview of current knowledge on the issues, methods, results, discussion and conclusions. Part of this work is to describe an animal experiment in the waking state, whose introduction to our department was one of the tasks of this graduate work.

Made available in DSpace on 2015-07-22T20:49:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-04-29. Added 1 bitstream(s) on 2015-08-11T03:26:25Z : No. of bitstreams: 1 Publico-256.pdf: 245625 bytes, checksum: 61276128685f362be02ff3b4eea05dbc (MD5) / A presente pesquisa visa estudar as repercussões materno-fetais da natação, na glicemia, triglicérides, ganho de peso e ingesta alimentar materna, além do número e peso dos filhotes ao nascimento. Foram utilizadas 24 ratas fêmeas Wistar adultas, com peso inicial de 235 gramas, sendo distribuídas em 4 grupos: controle grávida sedentária (CGS) (n=6), controle grávida treinada (CGT) (n=6), experimental grávida sedentária (EGS) (n=6), e experimental grávida treinada (EGT) (n=6). Foi utilizada a streptozotocina para a obtenção do diabetes no grupo experimental, e colocado as ratas para cópula, sendo a confirmação feita pela presença de espermatozóide no esfregaço. O controle da glicemia e triglicérides foram feitos nos quatro grupos, iniciando no dia zero de gestação (coleta 1), seguido do 7º (coleta 2), 14º (coleta 3) e 19º dia (coleta 4). O treinamento físico (natação) foi realizado cinco vezes por semana, por um período de 60 minutos, durante três semanas consecutivas até o dia do parto espontâneo. Foi realizado o controle do peso e ingestão alimentar materna diariamente, e após o nascimento, os filhotes foram contados e pesados. Observamos que, o exercício físico (natação) de moderada intensidade foi capaz de diminuir significantemente os valores glicêmicos, principalmente nas ratas prenhas diabéticas, apresentando também, benefícios no perfil dos triglicérides, além de não promover alterações sobre o feto. / This research aims to study the materno-fetal repercussion of the swimming on the glucose, triglycerides levels, weight gain and maternal food intake, and also the number and weight of offspring at birth. We used 24 Wistar adult female rats, with 235 g of initial weight, distributed into 4 groups: sedentary pregnant control (CGS) (n=6), trained pregnant control (CGT) (n=6), sedentary pregnant experimental (EGS ) (n=6) and trained pregnant experimental (EGT) (n=6). It was used streptozotocin-induceddiabetes in the experimental group, and the rats were paired for copulation, and the confirmation by the presence of sperm in the smear. The control of glucose and triglycerides levels were made in the four groups, starting from day zero of gestation (collection 1), followed by the 7th (collection 2), 14th (collection 3) and 19th days (collecting 4). The physical training (swimming) was performed five times a week (60 minutes), for three consecutive weeks until the day of spontaneous delivery. The maternal weight and food intake were daily controled, and after birth, the offsprings were counted and weighed. Therefore, physical exercise (swimming) of moderate intensity was able to significantly reduce the glycemic values, especially in pregnant diabetic rats, also, benefits in the profile of triglycerides, and not to promote change on the fetus. / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2014-06-11T19:32:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-01-10Bitstream added on 2014-06-13T21:05:31Z : No. of bitstreams: 1 melo_crm_dr_botfm.pdf: 282857 bytes, checksum: b93322b1d4fd06e5dda5714db163ab21 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A restrição hospitalar de alimentação e fluido oral para parturientes é uma tradição obstétrica fortemente organizada, justificada pelo risco de regurgitação e aspiração do conteúdo gástrico durante a anestesia. Estudos demonstram que independente do tempo da última refeição, o estômago nunca está completamente vazio, pois o jejum não elimina o conteúdo estomacal; pelo contrário, aumenta a concentração de ácido clorídrico, podendo o jejum prolongado causar aumento do volume gástrico e da acidez. Embora a infusão intravenosa seja necessária, em muitas circunstâncias obstétricas, para administração de medicamentos ou anestesia, o emprego de fluidos intravenosos de rotina não pode ser considerada um substituto completamente seguro de alimento e líquidos no trabalho de parto. Estudos comparam o esforço do trabalho de parto com o desempenho atlético como correr uma maratona, porém há carência de informação das necessidades nutricionais da parturiente e seu feto A normatização das práticas durante a assistência ao parto normal reflete a promoção do parto e nascimento saudáveis, porém observam-se ainda atitudes desvinculadas dos últimos achados científicos. / Oral fluid and dietary restriction for parturients in hospital settings is a highly organized obstetric tradition aimed at preventing regurgitation and aspiration of gastric matter from taking place during anesthesia. Studies have shown that, independently from the time of the last meal, the stomach is never completely empty because fasting does not eliminate stomach contents. Quite the contrary, there is an increase in chloridric acid. Besides, prolonged fasting may raise the level of gastric volume and acidity. Intravenous infusion is necessary, but when it comes to medication or anesthesia management, routine intravenous fluids may not work as well as food and liquids during obstetric labor. Some studies show that giving birth takes as much effort as running a marathon. Nevertheless, information about the nutritional needs of parturient and fetus is scarce. Although less scientific forms of labor management can still be found, concrete measures towards promoting a healthier labor can be taken by the standardization of the assistance to the mother in normal labor.

abstract: Background: Acetic acid in vinegar has demonstrated antiglycemic effects in previous studies; however, the mechanism is unknown. Objective: To determine whether acetic acid dissociates in the addition of sodium chloride and describe a flavorful vinaigrette that maintains the functional properties of acetic acid. Design: Phase I - Ten healthy subjects (23-40 years) taste tested five homemade vinaigrette and five commercial dressings. Perceived saltiness, sweetness, tartness, and overall tasted were scored using a modified labeled affective magnitude scale. Each dressing was tested three times for pH with a calibrated meter. Phase II – Randomized crossover trial testing six dressings against a control dressing two groups of nine healthy adult subjects (18-52 years). Height, weight and calculated body mass index (BMI) were performed at baseline. Subjects participated in four test sessions each, at least seven days apart. After a 10-hour fast, participants consumed 38g of the test drink, followed by a bagel meal. Capillary blood glucose was obtained at fasting, and every 30 minutes over a 2-hour period the test meal. Results: Dressing pH reduced as sodium content increased. In the intervention trials, no significant differences were observed between groups (p >0.05). The greatest reduction in postprandial glycemia (~21%) was observed in the dressing containing 200 mg of sodium. Effect size was large in both group 1 (η2=0.161) and group 2 (η2=0.577). Conclusion: The inclusion of sodium into acetic acid may impair its ability to attenuate blood glucose after a meal. / Dissertation/Thesis / Masters Thesis Nutrition 2017

Esse estudo teve como objetivo avaliar as alterações hemodinâmicas e do nível de glicemia decorrentes do uso do anestésico local articaína a 4% com epinefrina nas concentrações 1:100.000 (A100) e 1:200.000 (A200) em cirurgias periodontais na maxila, realizadas em diabéticos. Em relação aos anestésicos, foram avaliados: tempo de início de ação, duração da anestesia sobre os tecidos mole, analgesia pós-operatória, sangramento trans-operatório, qualidade da cicatrização, parâmetros hemodinâmicos e glicemia medidos durante as cirurgias. Para isso, 18 voluntários com idades entre 40 e 65 anos foram selecionados. Destes, 10 não apresentavam alterações sistêmicas (não diabéticos-não DM), enquanto 8 eram portadores de diabetes mellitus não insulinodependentes (DM), todos com condições periodontais semelhantes. Foram submetidos a cirurgias periodontais bilateralmente na região da maxila sob anestesia local com A100 e A200, de forma duplo-cega, randomizada e cruzada. O tempo cirúrgico foi semelhante para todos os grupos, e A100 e A200 mostraram-se igualmente eficazes para cirurgias periodontais. Foi utilizada quantidade idêntica de ambos anestésicos em todas as cirurgias (1 tubete; 1,8ml), o tempo cirúrgico foi semelhante em todos os procedimentos. O tempo de inicio de ação foi similar para todos, independentemente da concentração de epinefrina ou presença de diabetes. O tempo de duração da anestesia foi significativamente maior para os DM, sem haver correlação com a concentração de epinefrina. O sangramento trans-operatório foi significativamente maior nos pacientes diabéticos apenas na fase de incisão com A200. Nas demais fases, o sangramento foi muito semelhante entre DM e Não DM. A analgesia pós-operatória foi considerada excelente, refletindo na baixa ingestão de analgésicos (paracetamol), especialmente pelo grupo DM, independentemente da concentração de epinefrina. Quanto à cicatrização, não houve diferença entre os grupos. As mudanças transitórias nos parâmetros hemodinâmicos (frequência cardíaca-FC; pressão arterial-PA) tiveram pouco significado clínico, apesar de os diabéticos apresentarem certa tendência a elevação na PA nas fases de incisão e debridamento. Os diabéticos não apresentaram elevação da glicemia ao longo das fases cirúrgicas, independente da concentração de epinefrina presente na solução anestésica, ao passo que os não diabéticos mostraram que a maior concentração de epinefrina resulta num maior tempo para a normalização dos níveis glicêmicos. Concluindo, tais resultados mostram que A100 e A200 são equieficazes para a realização de cirurgias periodontais. Sendo assim, a utilização de anestésico com menor concentração de epinefrina (1:200.000) parece ser a melhor escolha para os indivíduos portadores de alterações sistêmicas como os diabéticos. / The present study compared the effect of articaine 4% associated with epinephrine in two different concentrations, 1:100.000(A100) and 1:200.000(A200), in periodontal surgeries performed in diabetic patients. We analyze hemodynamic parameters, blood glucose concentration, onset and duration of anesthetic action on soft tissues, intraoperative bleeding and wound healing. Eighteen volunteers, age range 40 to 65 years, with similar periodontal disease and conditions, were separate in two groups, type 2 diabetes mellitus (DM, 8 volunteers) or with no diabetes mellitus (Non DM, 10 volunteers). They´re submitted to a matched bilateral periodontal surgery in maxilla, under local anesthesia with either A100 or A200, in a double blind, randomized, crossed manner. The duration of surgery was the same for all groups, with A100 and A200 being equally effective for periodontal surgeries. Identical volumes of both anesthetic solutions were used (1 cartridge:1,8ml) in all surgeries. The anesthetic latency was similar in diabetics or non-diabetics for both epinephrine concentration. In diabetic patients the anesthetic duration was increased regardless the epinephrine concentration. Intraoperative bleeding only increased in diabetic patients with A200 during incision phase. The duration of postoperative analgesia was excellent, reflecting by a low intake of postoperative medications (paracetamol). Wound healing was relatively normal for all volunteers regardless the local anesthetic employed or presence of diabetes. The transient changes in blood pressure or hart hate were not clinically significant but the diabetic patients have some tendency to increase their blood pressure in some surgical phases. In diabetic subjects, blood glucose have no increase throughout surgical phases, regardless the epinephrine concentration present in the anesthetic solution, but the Non DM presents a prolonged time for normalize their blood glucose after A100. In conclusion, this study demonstrate that epinephrine concentration (1:100.000 or 1:200.000) in articaine 4% solution have the same efficacy for periodontal surgeries. Therefore, the formulation with a lower vasoconstrictor concentration (A200) seems to be the more adequate choice for patients with systemic diseases like diabetes.

Made available in DSpace on 2018-08-01T22:56:53Z (GMT). No. of bitstreams: 1 tese_7425_INGRID BROMERSCHENKEL.pdf: 1154542 bytes, checksum: 3423eda335571be10962af53db93b9b4 (MD5) Previous issue date: 2014-02-25 / Na clínica equina frequentemente se depara com a dificuldade de interpretar resultados de exames bioquímicos devido a escassas referências para a comparação. A glicose é o principal substrato utilizado pelo organismo para a realização de diferentes funções biológicas. A glicose sanguínea está em constante fluxo, sendo transportada a diversas partes do corpo e em cada espécie animal ocorrem variações da glicemia principalmente em função da idade, dieta e condições fisiológicas. A literatura cita inúmeros modelos matemáticos para estimativa de peso em cavalos, com base em medidas corporais e fitas métricas adaptadas. Entretanto, esses nem sempre são adaptados para todas as raças e idades, e algumas técnicas de estimativa de peso corporal reproduzem resultados mais precisos que outros dependendo desses fatores. Dessa forma, este estudo objetivou estabelecer as concentrações séricas proteicas de potros sadios da raça Mangalarga Marchador no período neonatal; avaliar a utilização do glicosímetro portátil para a mensuração da glicemia, considerando como controle os resultados mensurados por meio de teste laboratorial; determinar se a variação dos valores de glicemia mensurados pelo glicosímetro portátil esta de acordo com a Food and Drug Administration; determinar as concentrações plasmáticas de glicose durante o período neonatal utilizando-se o teste laboratorial; comparar quatro metodologias para a mensuração de peso e verificar a precisão de cada uma delas em relação ao peso real do animal mensurado em balança comercial. Não houve variação significativa das frações proteicas entre os momentos estudados. Os potros estudados não apresentaram alterações significativas nas concentrações glicêmicas durante o período neonatal. O glicosímetro portátil demonstrou precisão similar ao teste laboratorial na determinação dos níveis glicêmicos em potros neonatos. A média da taxa de erro do glicosímetro permaneceu dentro do limite exigido pela Food and Drug Administration. Em potros com 12 horas até 30 dias de idade pode-se adotar a F2 eFMAPE como método alternativo para mensuração de peso, já que os resultados de dessas metodologias não diferiram do obtido pela balança. / In equine clinic often faced with the difficulty of interpreting results of biochemical tests due to scant references for comparison. Glucose is the main substrate used by the body to perform different biological functions. Blood glucose is in constant flux, being transported to various parts of the body and within each animal species variations of glycemia primarily a function of age, diet and physical conditions occur. The literature cites a number of mathematical models to estimate horses weight, based on body measurements and adapted tapes generated by these models. However, these models or weight tapes are not always suitable for all breeds and ages, and some techniques for estimating body weight reproduce more accurate results than others depending on these factors. Thus, this study aimed to establish the protein serum concentrations in healthy foals Mangalarga Marchador the neonatal period; evaluate the use of portable glucometer for blood glucose measurements, considering how control the results measured by laboratory test and determine if the variation of glycemia measured by portable glucose is in agreement with the Food and Drug Administration; determine plasma glucose concentrations during the neonatal period using laboratory testing and; compare four methods for measuring weight and verify the accuracy of each in relation to the actual weight of the animal measured in trade balance. There was no significant variation of protein fractions between the times. The foals were no significant changes in glucose concentrations during the neonatal period. The portable glucose showed similar accuracy for laboratory test to determine glucose levels in neonatal foals. The average rate of glucometer error remained within the limits required by the Food and Drug Administration. And in foals 12 hours to 30 days old can adopt the F2 and FMAPE as an alternative method for measuring weight, since the results of any of these methodologies differ measured by the scales.