Very premature infants often experience high blood sugar levels as a result of incomplete metabolic development, illness, and stress. High blood sugar levels have been associated with a range of worsened outcomes and increased mortality, but debate exists as to whether high blood sugar levels are a cause of, or marker for, these worsened outcomes. Insulin can be used to lower blood sugar levels, but there is no standard protocol for its use in neonates, and the few clinical studies of insulin use in neonatal intensive care are relatively small and/or have resulted in high incidence of dangerously low blood sugar levels. Hence, there is a need for a safe and effective protocol for controlling blood sugar levels to a normal range in order that potential clinical benefits can be successfully studied in this clinical cohort. This thesis adapted a glucose-insulin model successfully used in adult intensive care for the unique physiology and situation of the very premature infant. The model aims to reflect known physiology. As such, sources and disposal of glucose and insulin within the body are examined using both published data and unique data sets from a study here in New Zealand. In addition, the absorption of glucose from milk feeds is examined. This glucose-insulin physiological model is then used alongside statistical forecasting to develop a protocol for selecting an appropriate insulin dose based on targeting of likely outcomes to a specified target normal range. The protocol is tested in silico using virtual trials, and then clinically implemented, with results showing improved performance over current clinical practice and other published studies. In particular, ~77% of blood glucose is observed within the specified target range across the cohort, and there has been no incidence of dangerously low blood glucose levels. This protocol is thus safe and effective, accounting for inter- and intra- patient variability, and thus enabling patient-specific care.

Thesis (MNutr (Interdisciplinary Health Sciences. Human Nutrition))--University of Stellenbosch, 2009. / Thesis presented in partial fulfillment of the requirements for the degree of Master of Nutrition at Stellenbosch University. / ENGLISH ABSTRACT: The glycemic index (GI) has proven to be a valuable nutritional tool in the management and prevention of diabetes and other chronic diseases of lifestyle 1,3,4,5,6,79,12,14,15. In this quantitative, cross-sectional, observational and descriptive study, the aim was to determine the knowledge and level of comprehension of South African registered dietitians with regard to GI and glycemic load (GL) as well as to determine their ability to use/implement the GI in the treatment of diabetes / insulin resistance. A questionnaire was emailed to 388 registered dietitians for completion. The questionnaire was based on relevant scientific literature and divided into three parts. The first part gathered demographical information about the participants, with special emphasis on where they had acquired their knowledge of GI principles. The second and third parts contained closed-end questions to which the participants were required to answer ‘true’ or ‘false’ or were presented with a multiple choice. Twenty-five questions specifically focused on the GI and the other 12 focused on GL. One hundred and fourteen subjects took part in the study. The results showed that most dietitians (54 %) did not learn GI principles at university and that the year that they qualified did not affect test results. The University attended did not seem to affect test results either, with the exception of Medunsa (Medical University of South Africa), where graduates scored on average significantly lower than the rest of the group). The test scores varied between 43% and 97%. The average test score for the group was 71% with those dieticians in private practice scoring the highest average (76%) compared to those working in other practice areas. Although 84% percent of participants reportedly used GI principles in their daily practice with patients, compared to only 33% who reportedly used GL principles, results showed no significant difference between knowledge or comprehension levels of GI and GL or the ability to implement GI or GL principles. To conclude, South African dietitians seem to have a good general knowledge of GI, but there is still room for improvement in order to ensure that dietitians can become experts in the field. It is recommended that curricula be revised to give this subject more attention during formal university training. / AFRIKAANSE OPSOMMING: Navorsing het bewys dat die Glukemiese Indeks (GI) ‘n waardevolle wetenskaplike hulpmiddel is in die voorkoming en bestuur van diabetes en ander chroniese siektes van lewenstyl 1,3,4,5,6,79,12,14,15 . Die doelwit in hierdie kwantitatiewe, dwars-snit, beskrywende studie was om die kennis- en begripsvlak van Suid-Afrikaanse dieetkundiges te toets rakende die GI en glukemiese lading (GL) asook hul vermoëns om hierdie beginsels toe te pas en te gebruik in die behandeling van diabetes en insulienweerstandigheid. ‘n Vraelys is aan 388 dieetkundiges gepos. Die vraelys was gebasseer op relevante wetenskaplike literatuur en het uit drie afdelings beslaan. Die eerste afdeling was ten doel om demografiese inligting oor deelnemers te bekom met spesifieke belang by die afkoms van hul kennis oor die GI. Die tweede en derde afdelings het bestaan uit vrae waarop ‘waar’ of ‘vals’ gemerk moes word of uit veelvuldige keuse vrae. Vyfen-twintig vrae het gefokus op die GI en twaalf vrae het gefokus op die GL. Eenhonderd-en-veertien persone het deelgeneem aan die studie. Die resultate het getoon dat meerderheid van die deelnemers (54%) nie die beginsels aangaande die GI op universiteit geleer het nie. Die jaar waarop graduasie plaasgevind het, het blykbaar nie ‘n invloed op uitkoms gehad nie, en die universiteit waar graduasie plaasgevind het, het ook nie die uitslag beïnvloed nie, uitsluitend Medunsa (waar gegradueerdes aansienlik swakker gevaar het as die res van die groep). Toets uitslae het gewissel tussen 43% en 97%. Die gemiddelde toetspunt was 71%. Dieetkundiges werkend in privaat praktyk het die hoogste gemiddelde toetspunt van 76% behaal in vergelyking met dieetkundiges wat in ander velde praktiseer. Ten spyte daarvan dat 84% deelnemers aangetoon het dat hulle GI beginsels in hulle werksomstandighede toepas, in vergelyking met slegs 33% wat GL beginsels toepas, was daar geen noemenswaardige verskil in uitkomste rakende deelnemers se kennis of begripsvlak van GI of GL, of hul vermoë om verwante beginsels toe te pas nie. Ter opsomming wil dit voorkom of Suid- Afrikaanse dieetkundiges oor ‘n goeie vlak van algemene kennis betrekkende die GI beskik. Daar is wel steeds ruimte vir verbetering om te verseker dat dieetkundiges as ware kenners op die gebied kan optree. Dit word aanbeveel dat universiteite se kurrikulums aangepas word om sodoende voorsiening te maak vir verbeterde voor-graadse opleiding oor die onderwerp.

The main aim of this thesis was to increase our understanding of the metabolic responses associated with short-term high-fat overfeeding. To this end, four separate studies are described in this thesis; each of which involved the provision of a high-fat, high-energy diet to young, healthy, lean individuals. The first of these experimental chapters (Chapter 2) determined the effects of a 7-day, high-fat (65%), high-energy (+50%) diet on postprandial metabolic and endocrine responses to a mixed meal challenge. This chapter demonstrates that 7-days of overfeeding impaired glycaemic control in our subject cohort but did not influence the response of selected gut hormones (acylated ghrelin, GLP-1 and GIP). In a mechanistic follow up study utilising stable isotope tracer methodology we then demonstrate that overfeeding-induced impairments in glycaemic control are attributable to subtle alterations in plasma glucose flux, rather than the overt tissue-specific adaptations (e.g. increased EGP, or reduced glucose disposal) that have previously been reported (Chapter 3). In an attempt to delineate the time-course of diet-induced impairments in glycaemic control, we then investigated the effects of 1-day of overfeeding (+80% energy with 73% of total energy coming as fat) (Chapter 4). Results demonstrate that a single day of overfeeding elicits responses which are comparable to 7-days of high-fat overfeeding; highlighting the rapidity with which excessive high-fat food intake can negatively influence glucose metabolism. In chapter 5 we utilised stable isotope tracer and muscle biopsy techniques to demonstrate that 7-days of high-fat overfeeding impairs glycaemic control but does not influence the fed-state mixed muscle protein fractional synthesis rate (FSR). In conclusion, the findings of this thesis demonstrate that while short-term high-fat overfeeding negatively influences whole-body glucose metabolism, skeletal muscle protein metabolism appears to be relatively unaffected in young, lean, healthy humans.

Abstract The aim of this study was to evaluate the treatment, course and outcome of pregnancy in Finland using two cohorts of diabetic women. The clinical cohort consisted of data from all 210 women with Type 1 diabetes and their 296 pregnancies managed between 1986 and 1995 in the two northernmost provinces of Finland. The register-based study population included all 1442 mothers with a singleton birth who had insulin treatment during pregnancy in 1991-1995 according to the Medical Birth Register. Of these mothers, 954 (66%) had pre-existing diabetes. Insulin-treated diabetes complicated 4.5/1000 births in Finland in 1991-1995, the prevalence of Type 1 diabetes being 2.9/1000 in the whole country and 3.3/1000 in Northern Finland. In the 1990's the care of these women shifted from tertiary level only to include the secondary level hospitals as well, and was more often carried out on an out-patient basis. This care policy in association with the self-monitoring of blood glucose levels contributed to an obvious improvement in glycaemic control during pregnancy. Despite that, the high proportion (73%) of women entering pregnancy with unsatisfactory glycaemic control did not decrease during the study period. Retinopathy complicated 134 (45.3%) diabetic pregnancies, while clinical nephropathy was found in 23 (7.8%) cases. Although retinopathy was more often aggravated during the first pregnancy, the occurrence of retinopathy or its severe form was not increased at the beginning of consecutive pregnancies. Of the mothers, 50 (16.9%) had pre-eclampsia during pregnancy, and in 28% of these cases it was classified as superimposed. It was found more often among primiparous than multiparous (25.6% vs. 11.0%, respectively), and its occurrence rose with the severity of diabetes. In both cohorts, the rates of preterm deliveries, Caesarean sections and large for gestational age (LGA) infants were significantly (p < 0.001) higher in Type 1 diabetic pregnancies than in the background population. The rates of congenital anomalies (CA) were 540-629/10000 in two study populations, both being 2-3-fold as compared to the background population. Cardiac malformations were most common, with anomalies in the genitourinary tract and the musculoskeletal organs being next in frequency. Sixty-three percent of malformed infants were boys. Though pregnancy itself was not found to worsen the prognosis of diabetes, at least in the short term, pregnancy in diabetic women still remains a high risk state with an increased rate of prematurity, operative deliveries, CAs and peri- and neonatal mortality. In order to decrease the mortality rate in diabetic births, attention should be directed at both the prevention of CA and at identifying the foetuses at risk for intrauterine death. The postneonatal mortality rate is also high, reflecting a shift in the deaths from the early neonatal period to a later age. Therefore, a combined mortality, including induced abortions, stillborns and infant deaths, would give a more realistic idea of the outcomes in diabetic pregnancies.

Au cours de l’administration simultanée de plusieurs médicaments injectables, sont utilisées une ligne principale de perfusion et une ou plusieurs ligne(s) en dérivation. La ligne principale est directement reliée au cathéter et permet l’administration des solutions utilisées pour l’apport hydro-électrolytique ou de maintenir une voie d’abord veineuse perméable. Les autres thérapeutiques vont être perfusées en dérivation de cette ligne principale. La prise en charge des patients relevant de soins intensifs et de réanimation nécessite une polymédication. Les traitements d’urgence impliquent majoritairement des médicaments à marge thérapeutique étroite. Lors de l’administration de médicaments en solutions concentrées, de faibles perturbations du débit d’administration peuvent engendrer de fortes perturbations cliniques et notamment, pour les médicaments vasoactifs, créer une instabilité hémodynamique. C’est pourquoi il est important d’étudier la problématique de la perfusion simultanée, de déterminer l’impact sur le débit massique des lignes de perfusion et la technique optimale des changements de seringues pour prévenir les variations intempestives du débit de perfusion. Ce mémoire présente un travail de développement et d’évaluation d’une démarche d’optimisation d’un système de perfusion complexe. Il consiste à étudier au travers d’évaluations in vitro et d’études cliniques la conception d’une ligne de perfusion en évaluant notamment un dispositif médical innovant afin de proposer, in fine, une solution applicable dans un service de soins intensifs. La première partie consiste à présenter l’ensemble des dispositifs médicaux de perfusion utilisés dans un département d’anesthésie-réanimation. La seconde partie s’intéresse à l’administration d’un médicament couramment perfusé sur la voie proximale: la noradrénaline. Les études in vitro, corroborées par des données cliniques, ont permis de montrer la supériorité de l’administration de noradrénaline à 0,5 mg/mL perfusée en Y avec une solution saline isotonique à débit fixe de 5 mL/h. Cette multiperfusion fait intervenir l’utilisation d’un prolongateur trois voies à faible volume résiduel, permettant d’optimiser les conditions de relais de seringues, connues comme étant à l’origine d’instabilités hémodynamiques chez les patients traités par catécholamines. Un programme hospitalier de recherche clinique interrégional est déposé dans le but d’établir des recommandations de perfusion des catécholamines.La troisième partie aborde l’administration des médicaments sur voie distale en sélectionnant l’insuline comme marqueur-médicament. Les résultats de cette étude clinique prospective randomisée contrôlée ont montré que l’utilisation d’un dispositif médical innovant, le dispositif Edelvaiss-Multiline 8 (Doran International) caractérisé par un tube multilumières à faible volume résiduel qui permet de dédier une voie à une seule thérapeutique, permettait de réduire significativement le temps passé en hypoglycémie pour 1000 heures de perfusion d’insuline au cours de perfusion continue d’insuline en soins intensifs périopératoires.Enfin, dans une dernière partie, les critères clés d’un montage optimisé de multiperfusion sont élaborés et sont mis en application dans un département d’anesthésie-réanimation dans le but d’optimiser et uniformiser la ligne de perfusion des patients. Ce travail a permis de valider les caractéristiques clés de la ligne de perfusion définis dans de précédentes études non cliniques : la nature du matériau des dispositifs médicaux utilisés, l’utilisation de valves appropriées, la minimisation des volumes internes des tubulures de perfusion, l’utilisation de systèmes de perfusion automatisés permettant de contrôler au mieux le débit d’administration des médicaments. / For the simultaneous administration of injectable drugs, the infusion line includes a main line with one or several derivative lines. The main line, which is directly connected to the catheter, is dedicated to hydration infusion or to maintain a permeable vein. Other medications will be added on the derivative lines.Intensive care unit patients frequently require lots of medications in the same time. Most of emergency drugs are substances with narrow therapeutic range. When concentrated solutions are employed, tiny mass flow rate disturbances can provoke clinical damages, such as haemodynamic instability. So, several parameters have been studied on simultaneous infusions: mass flow rate and syringes changeovers.The purpose of this work was to develop and optimize complex infusion line systems. An innovative infusion medical device has been evaluated in clinical trials and in vitro studies. The final objective was to design an optimized infusion line, which could be applied to ICUs.The whole medical devices used in ICUs was first listed. Then, noradrenaline has been used as the reference drug to study central venous catheter proximal line. A 0.5 mg/mL noradrenaline solution Y-infused with a saline (5mL/h) has been shown by clinical and in vitro data to be the best solution. Nevertheless, this conclusion was valid only with the use of a very low dead-space volume Y-extension set. Thanks to this device, syringe changeovers optimization is possible.The central venous catheter distal line has been studied in a second time through an open randomized controlled prospective clinical trial. Primary endpoint of the study was the impact of two different insulin infusion lines (Edelvaiss-Multiline 8, Doran International versus standard line) on glycaemic variability. Doran’s innovative device consists of an exten¬sion set with eight accesses connected to nine separated lumens in a single tube. This allows to dedicate an isolated way for insulin. With its use, a significant decrease of hypoglycaemia occurring in 1000h of infusion period was clinically demonstrated. Finally, all the data were synthetized to optimize an ICU multi-infusion line. The one, which has been designed for surgery and intensive care units, was tested on patients.To conclude, items responsible for mass flow rate disturbances have been identified: medical devices material, addition of appropriated valves, internal volume line minimization and use of automated infusion systems (as pumps). The ideal infusion line has to take into account all these parameters.

Four studies investigating the assessment of glycaemic control in cystic fibrosis are presented within this thesis. The first was a validation study of continual glucose monitoring (CGM) in cystic fibrosis (CF). 50 stable adults with CF underwent home CGM for 3 days, during which time they attended the CF centre for OGTT. Gold standard fasting (0 hour) plasma glucose and 2 hour plasma glucose values during OGTT were compared with concurrent CGM sensor glucose values using a 'limits of agreement' analysis. CGM was found to be valid in adults with CF, with its accuracy being consistent with that published in non-CF populations. The next investigation compared OGTT with CGM with several objectives: to determine whether OGTT is a relevant and adequate measure of glycaemia in CF, find out whether CGM could offer a superior alternative to OGTT and explore whether OGTT and CGM results are associated with prior change in lung function and weight in adults with CF. Data from the first study was used to show that the OGTT can only identify abnormal glycaemic control in CF at a late stage, and that CGM is a more relevant reflection of everyday glycaemia in CF. No correlation was found between prior change in lung function and nutritional status in CF and glycaemia measured by OGTT or CGM. The subsequent study investigated whether CGM could identify early abnormal glycaemic control in CF. This involved ten non-CF healthy controls undergoing the same study protocol as the 50 stable adults with CF, to determine 'normal' glycaemic control parameters. Of 25 CF patients with normal glucose tolerance by OGTT, 19 (76%) had significantly higher mean and/or variability of CGM levels than healthy controls. This lead to changes in their management, including 2 subjects being commenced on insulin therapy. The final investigation was a questionnaire study, asking the 50 CF patients to provide information on their experience of undergoing CGM. 58% of patients responded, with replies indicating that they found CGM broadly acceptable, interfering little in their lives and that their experiences were generally positive. This insight into patients' experiences of CGM can be used to guide future clinical and research roles for this tool. These studies have provided novel data regarding the assessment of glycaemic in CF. Information captured by CGM has greater relevance to CF patients' daily lives than OGTT. CGM can identify early problems with glycaemic control leading to changes in management that may not be detected by conventional measures. CGM offers potential in further clinical application and research to improve the lives and outcomes for adults with CF.

Yes / Smoking increases the risk of developing type 2 diabetes. However, several population studies also show a higher risk in people 3–5 years after smoking cessation than in continuing smokers. After 10–12 years the risk equates to that of never-smokers. Small cohort studies suggest diabetes control deteriorates temporarily during the first year after quitting. We examined whether or not quitting smoking was associated with altered diabetes control in a population study, for how long this association persisted, and whether or not this association was mediated by weight change. Methods We did a retrospective cohort study (Jan 1, 2005, to Dec 31, 2010) of adult smokers with type 2 diabetes using The Health Improvement Network (THIN), a large UK primary care database. We developed adjusted multilevel regression models to investigate the association between a quit event, smoking abstinence duration, change in HbA1c, and the mediating effect of weight change. Findings 10 692 adult smokers with type 2 diabetes were included. 3131 (29%) quit smoking and remained abstinent for at least 1 year. After adjustment for potential confounders, HbA1c increased by 0·21% (95% CI 0·17–0·25; p<0·001; [2·34 mmol/mol (95% CI 1·91–2·77)]) within the first year after quitting. HbA1c decreased as abstinence continued and became comparable to that of continual smokers after 3 years. This increase in HbA1c was not mediated by weight change. Interpretation In type 2 diabetes, smoking cessation is associated with deterioration in glycaemic control that lasts for 3 years and is unrelated to weight gain. At a population level, this temporary rise could increase microvascular complications.

The tiger nut (Cyperus esculentus) has attracted a lot of unsubstantiated health claims, yet there is a dearth of research investigation within Ghana specifically in the area of food product development. This study addresses the development of ‘functional bread and biscuit’ from tiger nuts obtained from UK market (Spain). The chemical constituents; carbohydrate, lipid, protein, dietary minerals and antioxidants, the functional properties of three varieties of tiger nuts obtained from Ghana (black and brown), Cameroon (yellow) and UK market (Spain) (brown) were investigated using standard analytical methods as well as the blood glucose response of healthy adults who consumed the developed bread. Tiger nuts were found to be good sources of carbohydrate (51-82g/100g) and lipids (21-37g/100g). The dietary fibre components ranged between 18, 1, 19 and 19g/100g for IDF, SDFP, HMWDF, and ITDF respectively, while the available carbohydrate as sugars were 45, 0.5 and 5g/100g for glucose, maltose and xylose respectively. Minerals that were found to be inherent to the crop were; potassium, phosphorus, magnesium, copper, iron, zinc and selenium and do not depend on place of origin. The following ratios for Sodium/Potassium 0.04, Calcium/Phosphorus 0.13 and Calcium/Magnesium 0.28 were obtained. Tiger nuts had TPC ≥ 134GAE per g, DPPH and stability index of 0.9-8.7mmol/litre and 3- 4 respectively. In conclusion the tiger nuts originating from different geographical locations were good sources of health giving minerals and had diversity of physical properties and chemical constituents which could inform future research in the functional food industry. Tiger nut could be added to the Ghana food basket and the product developed from it could be a potential functional food because of its effect on glucose response and phytochemical contents. It could again be used to replace artificial antioxidants (BHA or BHT) which are used in the food industry to inhibit lipid and protein oxidation especially the black variety.

Thesis (M.Ing. (Mechanical Engineering))--North-West University, Potchefstroom Campus, 2007.

Poorly controlled diabetes is common among the majority of youth with type 1 diabetes and can lead to adverse health outcomes at an early age. There is a need to change this to minimise the risk of negative long-term consequences. The onset of complications from diabetes can be prevented or delayed with good management as demonstrated by blood glucose being kept close to or within the normal range. Diabetes control is challenging for young people due to a combination of physiological and psychological factors. Diabetes control needs to be monitored both at an individual level and also at a population level, in order to optimise health outcomes and provide important information for health service provision. There are gaps in knowledge relating to the current level of diabetes control at a population level and of the epidemiological characteristics of youth with type 1 diabetes in the Canterbury region in New Zealand. There has been no research of this nature in the Canterbury region since 2003. There are also gaps in knowledge and a lack of national and international research that investigates psychosocial characteristics of youth with type 1 diabetes and the impact these may have on diabetes control. There is a potentially promising intervention, namely, Motivational Interviewing (MI), that although previous research investigating it with diabetes has shown some promise, methodological problems have limited the conclusions that can be drawn. This thesis, within the New Zealand context, addresses some of these gaps and adds to the body of knowledge of research concerning diabetes control and youth with type 1 diabetes, and investigates MI intervention for youth with poorly controlled diabetes. The thesis encompasses three studies. The first study is an audit that provides up-to-date information on epidemiological characteristics and clinical outcomes for the youth population with type 1 diabetes residing in the Canterbury region. The second study is a cross-sectional study that investigates the relationship between glycaemic control and key psychosocial characteristics: illness beliefs, self-efficacy, and quality of life in youth with type 1 diabetes in Canterbury. The third study is a longitudinal study that investigates the efficacy of MI as an intervention for youth with poorly controlled type 1 diabetes, and explores its impact on diabetes outcomes using statistical and clinical analyses. The first study showed that from 2003 to 2010 the prevalence of adolescents and young adults with type 1 diabetes in Canterbury has increased; there is therefore an increased demand on health resources. In addition, in 2010 glycaemic control at a population level was in the poorly controlled diabetes range and this had remained unchanged since 2003. This suggests the need for more intensive interventions. The second study found that poor diabetes control in youth with type 1 diabetes is influenced by a number of factors, including negative views on diabetes, lower perceived personal control, higher diabetes-related concerns, and lower levels of worry about complications. These findings provide a new understanding of the importance of balancing worries about diabetes complications and the perception of diabetes as a threatening condition. The third study showed that the MI intervention was generally successful in improving diabetes outcomes – clinical, psychosocial, and behavioural changes were observed. Statistically and clinically significant positive changes were found across multiple variables: glycated haemoglobin (HbA1c), glycaemic variability, adherence, and psychosocial functioning. Taken together, the findings of the three studies indicate that majority of youth with type 1 diabetes in the Canterbury region had poor glycaemic control, which suggests that additional interventions may be required to improve management of their condition, especially interventions targeting psychosocial functioning (e.g., illness perceptions) and diabetes self-management. Motivational Interviewing may be a viable option, and therefore further research into this approach is recommended.