Obesity is characterized by hyperinsulinemia and chronic inflammation, contributing to insulin resistance and type 2 diabetes (T2D) risk. Pattern recognition receptors (PRRs) of the innate immune system, including Toll-like Receptors (TLRs) and Nod-like Receptors (NLRs), have been identified as propagators of metabolic inflammation. Circulating bacterial components exert distinct effects on inflammation and insulin sensitivity via TLRs and NLRs. Specific types of bacterial peptidoglycan engage NOD1 and NOD2. Activators of NOD1 increase inflammation and insulin resistance, while activators of NOD2 promote immune tolerance and insulin sensitivity. NOD1 and NOD2 use the common downstream adaptor RIPK2 to drive immune responses, but the role of RIPK2 in glucose homeostasis was unknown. RIPK2 is positioned to mediate effects of xenobiotics and microbial components on blood glucose. For example, tyrosine kinase inhibitors (TKIs) are being investigated for diabetes treatment. Improvements in blood glucose control have been observed in diabetic cancer patients receiving TKI therapy but the mechanism underlying these changes remains unclear. Several TKIs inhibit RIPK2. We sought to understand if TKIs that inhibit RIPK2 block inflammatory and metabolic consequences of NOD signalling. We hypothesized inhibition of inflammation via NOD1-RIPK2 by certain TKIs contributes to lowered blood glucose/improved insulin sensitivity in pre-clinical models of obesity. We showed that RIPK2 was required for acute glycemic consequences of NOD1 and NOD2 activation, and RIPK2-specific TKIs attenuated these glycemic effects. We found TKI-mediated improvements in blood glucose are independent of NOD-RIPK2 signalling during diet-induced obesity. However, RIPK2 mediated the effects of certain TKIs on blood insulin. Finally, we tested if RIPK2 mediated the effects of bacterial components derived from commensal microbiota. We found injection of upper intestinal microbe components lowered blood glucose via NOD2-RIPK2 signalling. These findings demonstrate that modulation of RIPK2 signalling by xenobiotic or microbial factors is an important contributor to blood glucose and insulin homeostasis. / Thesis / Doctor of Philosophy (PhD) / Obesity increases the risk of chronic diseases, including Type 2 Diabetes (T2D). Obesity stops insulin from working properly, leading to the inability to lower blood glucose. Obesity and T2D are linked to chronic, low-grade activation of the immune system. The immune system normally defends the body against microbes by inducing a pro-inflammatory response. Inflammation can also be activated or inhibited by drugs (xenobiotics), and different aspects of inflammation can increase or decrease blood glucose and insulin. A major unanswered question was how certain cancer drugs and bacterial components interact with the immune system to change blood glucose or insulin. This work tested how an innate immune pathway that detects bacterial cell wall components is influenced by cancer drugs and alters blood glucose and insulin in pre-clinical models. This work is targeted at understanding how new prebiotics or existing drugs can be tasked as therapeutic strategies for prediabetes and T2D.

Both in type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of ?-cells, leading to the impaired insulin secretion. Thus, the search for agents to protect b-cell and enhance its function is important for diabetes treatment. Studies have reported that baicalein, a flavone originally isolated from the roots of Chinese herb Scutellaria baicalensis, has various claimed beneficial effects on health, such as anti-oxidant, anti-viral, anti-thrombotic, and anti-inflammatory effects. However, it is unclear whether it exerts an anti-diabetic action. Here, we present evidence that baicalein may be a novel anti-diabetic agent. Specifically, dietary intake of baicalein significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in high-fat diet (HFD)-fed middle-aged diabetic mice, which was associated with the improved isle t?-cell survival and mass. Baicalein treatment had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in HFD-fed mice. In in-vitro studies, baicalein significantly augmented glucose-stimulated insulin secretion in insulin-secreting cells (INS1) and promotes viability of INS1 cells and human islets. These results demonstrate that baicalein may be a naturally occurring anti-diabetic agent by directly modulating pancreatic?-cell function. / Master of Science

Type 2 diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia, insulin resistance, and the dysfunction of β-cells. While there are several therapies for T2D, there is no effective treatment that can reverse the functional decline of pancreatic β cells in T2D patients. Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by human intestinal L cells, which can stimulate the proliferation and differentiation of β cells and promote glucose-stimulated insulin secretion (GSIS), thereby playing a critical role in maintaining glycemic homeostasis. Recently, GLP-1-based medications have been developed for treating T2D. However, most of the GLP-1-based drugs are expensive and have significant adverse effects. Therefore, development of safer and more convenient agents that can mimic the physiologically fed state to promote endogenous GLP-1 secretory function of intestinal L-cells to improve glucose homeostasis holds great potential for the prevention and treatment of T2D. This project aimed to examine whether natural compound genipin promotes intestinal GLP-1 secretion and exerts anti-diabetic effects. I found that genipin rapidly increased GLP-1 secretion from intestinal L-cells, with 10 and 100 μM concentration inducing significant incretin hormone release. L-cells exposed to genipin displayed a rapid increase in intracellular [Ca²⁺]i and the activity of phospholipase C (PLC). Inhibition of PLC ablated genipin-stimulated Ca²⁺] increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from the cells depends on the PLC/Ca²⁺ pathway. In vivo, genipin reduced the non-fasting and fasting blood glucose levels, improved insulin resistance, and protected again high fat diet-induced liver damage. All together, these data indicate that genipin is a naturally occurring anti-diabetic agent, which could be a pharmaceutical lead for developing anti-diabetic drugs. / M.S. / More than 34 million Americans are suffering from diabetes, with over 90% of these cases being type 2 diabetes (T2D). Loss of β-cell mass and function is central to the deterioration of glycemic control over time in T2D. Therefore, preservation or improvement of β-cell mass and its insulin secretory function could prevent and treat T2D. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing functional decline of pancreatic β-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a critical role in maintaining glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell proliferation. This present work is to determine whether natural compound genipin promotes intestinal GLP-1 secretion and thus exerts anti-diabetic effect.

The elderly population is increasing at a rapid rate each year, and with the increase in the elderly population there is a need for better medical assistance and devices. The greatest problem this demographic is facing is the ability to age in place. More elderly people are being placed in nursing homes, assisted living homes, moving in with relatives due to disabilities or fear of disabilities caused by a life threaten event such as heart disease, stroke, falling/fainting, or uncontrolled glucose levels. Falling is the number one leading cause of deaths, injuries and incapacity in the elderly. Stroke is the 3rd leading cause of death in the U.S; it is the 2nd leading cause worldwide. Rapid change in glucose levels is another leading cause of disabilities and deaths. Heart disease is the 2nd leading cause of death in the elderly. These life threatening events can be prevented and if treated early enough can allow the person to have a full recovery and continue to age in place. A device was proposed that could monitor these four life threatening events: heart disease, stroke, falling/fainting and changes in glucose levels. This device will monitor the user continuously. Research was conducted to see what other products are on the market and how they detect these events and how reliable they are for the user. A literature review was performed to understand what other people are doing to solve the aging in place problem. Using this and needs assessment of the elderly, the system architecture for the wrist worn device was designed along with a testing plan and procedure. More research needs to be done in certain areas to better improve solutions and technology in the area aging in place of the elderly. Before this device can bridge some of the gaps between the current issues and the solution the device will have to be tested for several things such as its ability to differentiate between stimulated falling/fainting and fall like activities such as sitting then lying. The orientation and position will be tested to see if the device can actually tell where the person is located. The device will have to be tested against well-known devices and see if it gives similar precise and accurate readings in real time. / Master of Science

BACKGROUND: The half-time (HT) period of a soccer match is viewed as a period for recovery. Completely inactive and passive HT has implications on metabolic responses and subsequent performance during the initial phases of the second half. PURPOSE: Determine the effects of an active rewarm-up, compared to a passive period, at halftime on various measures of performance during the first 15-minutes of the second half using global positioning system (GPS) units. Identify the effects of the active versus passive HT period, with CHO beverage supplementation, on blood parameters. METHODS: Crossover design study, twenty collegiate male soccer players participated in two 90-minute soccer matches with passive rest (CON) or a moderate-intensity rewarm-up (RWU) during HT with CHO supplementation. Subjects received five fingerstick blood samples throughout the match (BG) and four subjects had serum insulin/BG taken three times during the match. RESULTS: RWU had significantly (p<0.05) higher measures for total distance, average speed, speed exertion, accelerations, HMP distance, decelerations, and EE during TI-4 half when compared to CON. No subjects experienced hypoglycemia. However, CON did have a significant drop in BG after HT and the lowest mean BG taken at 60-minutes. Tendency for CON and RWU to have HT insulin levels that were elevated and reduced, respectively. CONCLUSION: A passive HT period is not optimal, given its causal role in temporary physical performance deficits in the second half of soccer matches. The results provide a strong rationale for collegiate soccer players and teams to incorporate the 8-minute RWU into the HT regime to optimize second half performance. / Master of Science / The half-time (HT) period of a soccer match is commonly viewed as a period of rest and recovery. A completely inactive HT period has metabolic and performance implications during the initial phases of the second half. A transient reduction in blood glucose (BG) concentrations could contribute to the second half performance decrement. The purpose of this study was to determine the effects of an active rewarm-up, compared to a passive period, at halftime on various measures of performance using global positioning system (GPS) units. Additionally, identify the effects of the active versus passive half-time period, with carbohydrate (CHO) beverage supplementation, on blood parameters. In a crossover design study, twenty collegiate male soccer players participated in two 90-minute soccer matches that included a passive rest (CON) or a moderate-intensity rewarm-up (RWU) during the 15-minute HT period with the consumption of a CHO beverage. Each subject received five finger stick blood samples throughout the match to monitor plasma blood glucose and a subset of four subjects had serum insulin taken three times during the match. The study found that an active HT, compared to passive, mixed with CHO supplementation significantly improved physical performance at the start of the second half. A passive HT period is not advised or optimal, given its causal role in temporary physical performance deficits in the second half of soccer matches. The results from this study provide a strong rationale for collegiate soccer players and teams to incorporate the 8- minute moderate-intensity into the HT regime in order to optimize second half performance.

Diabetes mellitus is one of the metabolic disorders prevailing all the over world. About 381.8 million people are affected by diabetes mellitus (DM) during 2013 and it is estimated to increase to 80% by 2035. Nephropathy, retinopathy, neuropathy and cardiovascular diseases are common complications arise in the patients suffering from diabetes Type I and Type II. Continuous monitoring of glucose will give greater clinical acumen on glucose metabolism of patients than conventional intensified glucose monitoring. It benefits patients to plan their meals and insulin dosages to prevent hypo-and hyperglycemia. Diabetes is a major cause of chronic kidney disease (CKD). Chronic kidney disease increases the risk of cardiovascular diseases (CVD). CVD and CKD are strongly intertwined. Urea and potassium are the major markers used in the diagnosis of chronic kidney disease and cardiovascular disease, respectively. Continuous monitoring of urea and potassium will help to initiate appropriate medical intervention to decelerate the progression of chronic kidney disease and cardiovascular disease. Conventional invasive blood withdrawal procedure has potential risks like infection, pain and discomfort to the patients. Moreover, invasive techniques deter periodic blood sampling as it requires for frequent vascular puncturing. At present, no medical device is available for continuous monitoring of blood analytes non-invasively. Present investigations aim at developing a non-invasive technique for monitoring blood analytes (glucose, urea and potassium) which have great potential to use as a point of care diagnostics. Interstitial fluid bathes the cells of the body and it is ultrafiltrate of plasma. It contains ions like potassium, sodium, etc., and neutral molecules like glucose, urea, etc. Analytes (glucose, urea and potassium) level in interstitial fluid equilibrates with blood with lag time of 0 – 15 minutes. Reverse iontophoresis is a process in which a small current is applied through the skin to enable the transdermal extraction of interstitial fluid. Reverse iontophoresis is a non-invasive method and it is suitable for developing an integrated system to extract and analyze the extracted analyte. It enables frequent analyte sampling in high risk patients like elderly and paediatric with more comfort than conventional methods. In the present work, investigations are conducted on non-invasive monitoring of blood glucose, urea and potassium using reverse iontophoresis (RI). As part of experimental investigations, in vitro models are developed. In vitro investigations are conducted to optimize the reverse iontophoresis parameters current density and time of extraction. With these optimized parameters, the in vivo investigations are conducted on human subjects. A dedicated instrumentation suitable for extraction of analytes is developed. Screen printed electrochemical glucose sensors suitable for revere iontophoresis applications are developed using mediated carbon ink. Glucose oxidase is immobilized on screen printed sensor using cross linking method. Electrochemical and material characterization studies are conducted on the developed sensors. The obtained results confirm that the suitability of developed sensor can be used for serum glucose measurement as well as for reverse iontophoresis. Screen printed potentiometric urea biosensors are also developed to monitor the blood urea level non-invasively using reverse iontophoresis. The extraction and sensing system consists of a reverse iontophoresis electrodes, a working electrode, and a reference electrode. Unease enzyme is immobilized in the polypyrrole matrix on the working electrode using cyclic voltammetry. The electrochemical and material characterizations are conducted on screen printed sensors. The sensitivity, selectivity and sensing range of sensors show that they have a potential application in reverse iontophoresis applications. The in vitro models are used to evaluate the developed (urea and glucose) sensors. They are further validated by this conducting the clinical investigations on 15 human subjects. A correlation between blood analyte (glucose and urea) level and transdermally extracted analytes (glucose and urea) is established. It is attempted to integrate both the sensors (glucose and urea) and evaluated their performance on human subjects. The effect of potassium present in the stratum corneum of skin during reverse iontophoresis is investigated by conducting in vivo studies on human subjects. Tape stripping technique is used to detect the presence of potassium in stratum corneum. Reverse iontophoresis investigations with and without passive diffusion are also conducted to analyze the effect of potassium in stratum corneum. Skin impedance is measured during reverse iontophoresis in order to study the effect of reverse iontophoreteic current on skin properties. The clinical investigations are conducted on human subjects to validate the performance of the developed sensors (glucose and urea) with the approval of Institute Human Ethical Committee (IHEC), IISc, Bangalore. Non-invasive monitoring of blood analytes (glucose and urea) on human subjects is successfully demonstrated with the indigenously developed sensors through reverse iontophoresis.

Critically ill patients often exhibit abnormal glycaemia that can lead to severe complications and potentially death. In critically ill adults, hyperglycaemia is a common problem that has been associated with increased morbidity and mortality. In contrast, critically ill infants often suffer from hypoglycaemia, which may cause seizures and permanent brain injury. Further complicating the matter, both of these conditions are diagnosed by blood glucose (BG) measurements, often taken several hours apart, and, as a result, these conditions can remain poorly managed or go completely undetected. Emerging ‘continuous’ glucose monitoring (CGM) devices with 1-5 minute measurement intervals have the potential to resolve many issues associated with conventional intermittent BG monitoring. The objective of this research was to investigate and develop methods and models to optimise the clinical use of CGM devices in critically ill patients. For critically ill adults, an in-silico study was conducted to quantify the potential benefits of introducing CGM devices into the intensive care unit (ICU). Mathematical models of CGM error characteristics were implemented with existing, clinically validated, models of the insulin-glucose regulatory system, to simulate the behaviour of CGM devices in critically ill patients. An alarm algorithm was also incorporated to provide a warning at the onset of predicted hypoglycaemia, allowing a virtual dextrose intervention to be administered as a preventative measure. The results of the in-silico study showed a potential reduction in nurse workload of approximately 75% and a significant reduction in hypoglycaemia, while also providing insight into the optimal rescue dose size and resulting dynamics of glucose recovery. During 2012, ten patients were recruited into a pilot clinical trial of CGM devices in critical care with a primary goal of assessing the reliability of CGM devices in this environment, with a specific interest in the effects of CGM device type and sensor site on sensor glucose (SG) data. Results showed the mean absolute relative difference of SG data across the cohort was between 12-24% and CGM devices were capable of monitoring some patients with a high degree of accuracy. However, certain illnesses, drugs and therapies can potentially affect sensor performance, and one particular set of results suggested severe oedema may have affected sensor performance. A novel and first of its kind metric, the Trend Compass was developed and used to assesses trend accuracy of SG in a mathematically precise fashion without approximation, and, importantly, does so independent of glucose level or sensor bias, unlike any other such metrics. In this analysis, the trend accuracy between CGM devices was typically good. A recent hypothesis suggesting that glucose complexity is associated with mortality was also investigated using the clinical CGM data. The results showed that complexity results from detrended fluctuation analysis (DFA) were influenced far more by CGM device type than patient outcome. In addition, the location of CGM sensors had no significant effect on complexity results in this data set. Thus, while this emerging analytical method has shown positive results in the literature, this analysis indicates that those results may be misleading given the impact of technology outweighing that of physiology. This particular result helps to further delineate the range of potential applications and insight that CGM devices might offer in this clinical scenario. In critically ill infants, CGM devices were used to investigate hypoglycaemia during the first 48 hours after birth. More than 50 CGM data sets were obtained from several studies of CGM in infants at risk of hypoglycaemia at the Waikato hospital neonatal ICU (NICU). In light of concerns regarding CGM accuracy, particularly during the first few hours of monitoring and/or at low BG levels, an alternative, novel calibration scheme was developed to increase the reliability of SG data. The recalibration algorithm maximised the value of very accurate calibration BG measurements from a blood gas analyser (BGA), by forcing SG data to pass through these calibration BG measurements. Recalibration increased all metrics of hypoglycaemia (number, duration, severity and hypoglycaemic index) as the factory CGM calibration was found to be reporting higher values at low BG levels due to its least squares calibration approach based on the assumption of a less accurate calibration glucose meter. Thus, this research defined new calibration methods to directly optimise the use of CGM devices in this clinical environment, where accurate reference BG measurements are available. Furthermore, this work showed that metrics such as duration or area under curve were far more robust to error than the typically used counted-incidence metrics, indicating how clinical assessment may have to change when using these devices. The impact of errors in calibration measurements on metrics used to classify hypoglycaemia was also assessed. Across the cohort, measurement error, particularly measurement bias, had a larger effect on hypoglycaemia metrics than delays in entering calibration measurements. However, for patients with highly variable glycaemia, timing error can have a significantly larger impact on output SG data than measurement error. Unusual episodes of hypoglycaemia could be successfully identified using a stochastic model, based on kernel density estimation, providing another level of information to aid decision making when assessing hypoglycaemia. Using the developed algorithms/tools, with CGM data from 161 infants, the incidence of hypoglycaemia was assessed and compared to results determined using BG measurements alone. Results from BG measurements showed that ~17% of BG measurements identified hypoglycaemia and over 80% of episodes occurred in the first day after birth. However, with concurrent BG and SG data available, the SG data consistently identified hypoglycaemia at a higher rate suggesting the BG measurements were not capturing some episodes. Duration of hypoglycaemia in SG data varied from 0-10+%, but was typically in the range 4-6%. Hypoglycaemia occurred most frequently on the first day after birth and an optimal measurement protocol for at risk infants would likely involve CGM for the first week after birth with frequent intermittent BG measurements for the first day. Overall, CGM devices have the potential to increase the understanding of certain glycaemic abnormalities and aid in the diagnosis/treatment of other conditions in critically ill patients. This research has used a range of prospective and retrospective clinical studies to develop methods to further optimise the use of CGM devices within the critically ill clinical environment, as well as delineating where they are less useful or less robust. These latter results clearly define areas where clinical practice needs to adapt when using these devices, as well as areas where device makers could target technological improvements for best effect. Although further investigations are required before these devices are regularly implemented in day-to-day clinical practice, as an observational tool they are capable of providing useful information that is not currently available with conventional intermittent BG monitoring.

Better disease care behaviors in youth with type 1 diabetes (T1D) are strongly related to better metabolic control (HbA1c). However, HbA1c results are only available, on average, every three months, and may not accurately capture intricacies of blood glucose fluctuations. Youth then must rely on blood glucose levels obtained throughout the day to determine which disease care behaviors to perform to maintain optimal metabolic control. Youth may have difficulty performing these disease care behaviors properly or consistently, which makes parental monitoring a crucial aspect of the diabetes regimen. Additionally, youth who experience frequent or severe hypoglycemia may develop a fear of hypoglycemia, which may impact their disease care behaviors and blood glucose levels directly. Average blood glucose levels strongly related to HbA1c which verifies HbA1c as a good indicator of average blood glucose levels. The Average Daily Risk Range (ADRR) index had a stronger relation to HbA1c than Mean Amplitude of Glycemic Excursions (MAGE) index; however, the percentage of blood glucose levels below, within, and above range may be the best indicator of glycemic variability, as it is more easily calculated and understood. More parental monitoring related to more diabetes prevention behaviors but not intervention behaviors or less glycemic variability.

Os valores de glicemia considerados fisiológicos em recém-nascidos, assim como os valores considerados patológicos, levando a danos no sistema neurológico, são bastante debatidos na literatura e há pouco consenso. O objetivo deste trabalho foi analisar a glicemia de 172 recém-nascidos adequados para a idade gestacional, a termo e em aleitamento materno exclusivo, no primeiro dia de vida, através de monitor contínuo de glicemia intersticial, que registra a glicemia a cada 5 minutos. O aparelho foi retirado após 24 horas e os resultados foram analisados em programa de computador. A amostra apresentou glicemia média de 66,6 mg/dl logo após o nascimento, com redução até a sexta hora de vida, com o valor de 53,7 mg/dl. Apenas na decima quarta hora de vida, a glicemia voltou a atingir valores entre 60 e 70 mg/dl. A média da glicemia dos recém-nascidos, durante o primeiro dia de vida, foi de 60,1 mg/dl (+/- 8,3). Da amostra, 63,9% apresentou uma ou mais medidas iguais ou menores que 50 mg/dl, 16,3% apresentou uma ou mais medidas iguais ou menores que 40 mg/dl; 4,6% apresentou uma ou mais medidas iguais ou menores que 30 mg/dl e 1,2% apresentou uma ou mais medidas iguais ou menores que 20 mg/dl. Os resultados mostraram um padrão de glicemia para essa casuística, com glicemia que cai rapidamente do nascimento até a sexta hora de vida e volta a subir até a decima quinta hora, ao atingir um valor que permanece estável até o final do dia. Este estudo permitiu elaborar uma curva de evolução dos valores de glicemia intersticial, com média e dois desvios padrões acima e abaixo. A porcentagem de recém-nascidos com a glicemia igual ou abaixo de 40 mg/dl, nesse estudo, comparada a outros estudos utilizando dosagem intermitente, mostrou que a monitorização contínua é capaz de detectar maior ocorrência de valores abaixo de 40 mg/dl. Recém-nascidos com valores de glicemia igual ou abaixo de 30 mg/dl estão abaixo da curva de normalidade traçada nesse estudo e devem, posteriormente, serem estudados em estudo prospectivo. A curva de evolução dos valores de glicemia pode contribuir para o estabelecimento de padrão de valoresglicêmicos durante as primeiras 24 horas de vida em recém-nascidos nascidos a termo, adequados a idade gestacional e sem agravos no período neonatal. / The values of glycemia that are considered physiological in neonates, as well as those considered pathological (that is, leading to damages in the neurological system) are widely debated in literature, and there is little consensus. The objective of this study was to analyze the glycemia of 172 appropriate for gestational age term newborns, who were exclusively breastfed, on the first day of life, through a continuous glucose monitoring device, which calculates interstitial glycemia every 5 minutes. The device was removed after 24 hours, and the results were analyzed in a computer program. The sample had a mean glycemia of 66.6 mg/dl shortly after birth, with a reduction until 6 hours of life, reaching a value of 53.7 mg/dl. At only 14 hours of life, the blood glucose returned to values between 60 and 70 mg/dl. The mean blood glucose of the newborns during the first day of life was 60.1 mg/dl (+/- 8.3). 63.9% of the sample had one or more values of glycemia equal to or lower than 50 mg/dl, 16.3% had one or more values equal to or lower than 40 mg/dl. 4.6% had one or more values equal to or lower than 30 mg/dl and 1.2% had one or more values equal to or lower than 20 mg/dl. The results present the glycemia pattern considered physiological for this sample, with glycemia that falls rapidly from birth up to 6 hours of life and goes back up to 15 hours, reaching a value that remains stable until the end of the first day. This study allowed the development of an evolution curve of interstitial glycemia values, with mean and two standard deviations above and below it. The percentage of newborns with glycemia at or below 40mg/dl in this study, compared to other studies using intermittent dosing, showed that continuous monitoring is able to detect a higher occurrence of values below 40 mg/dl. Newborns with blood glucose values equal to or lower than 30 mg/dl are below the normality curve plotted in this study and should be further studied in a prospective study. The evolution curve of the glycemia values may contribute to the establishment of glycemic values during the first 24 hours of life in term newborns who are appropriate for gestational age and didn\'t present any conditions in the neonatal period.

Este trabalho contribui para o projeto de um sistema não-invasivo capaz de quantificar o nível de glicose no sangue através de imagens da íris humana, o projeto recebeu o nome de GlucoÍris. Este foi desenvolvido pelo Departamento de Engenharia Mecânica (LabMetro), da Universidade Federal de Santa Catarina (UFSC) onde foi concebido e avaliado um sistema óptico/mecânico e um programa de computador para extrair parâmetros quantitativos associados à coloração e estrutura da íris humana. Um primeiro protótipo de dispositivo capaz de adquirir imagens digitais coloridas da íris foi desenvolvido juntamente com uma primeira versão de um programa de computador. Alterações na íris com 24 voluntários foram avaliadas. Os resultados atingidos em trabalhos anteriores mostraram que, de fato, a cor da imagem de uma íris sofre alterações em função de variações no nível de glicose na corrente sanguínea, indicando que é possível medir a glicemia através da íris humana. Partindo-se dos resultados das fases anteriores do projeto, este trabalho se dedicou em desenvolver um sistema, utilizando redes neurais, para se fazer uma estimação/previsão do valor de glicemia através de análises de imagens da íris humana. Com os dados de cor extraídos das imagens e os valores de glicemia conhecidos, para os casos estudados, avaliou-se a capacidade da rede em estimar novos valores de glicemia para os voluntários em questão. / This work contributes to the project of a non-invasive system which is able to quantify the glucose level in the blood through the human iris images; the project was named GlucoÍris. It was developed by the mechanical engineering department (LabMetro) of the Federal University of Santa Catarina (UFSC) where it was placed and analyzed an optical/mechanical system. Also, it was created a computer program to find out quantitative parameters associated with the color and the structure of the human iris. Together with the prime version of a computer program it was developed an earliest prototype of the apparatus which was able to obtain digital colored images of the iris. The alterations found out in the iris of the twenty-four volunteers where evaluated. Actually, due to the variations of the glucose level in the blood, previous studies showed that the color of the image of an iris experiences changes, indicating that it is possible to measure the sugar rate in the blood through the human iris. Applying the results of previous stages of the project, the purpose of this study was to develop a system, using neural networking, to estimate the blood glucose rate through the analysis of the images of the human iris. Employing the color data found in the images and the known blood glucose amount on the studied cases, it was evaluated the networking ability to estimate new sugar rates in the mentioned volunteers\'s blood.