Magister Chirurgiae Dentium (MChD) / Chronic inflammation of the periodontium is known as periodontal disease. The inflammation can be contained only within gingival connective tissue or can progress, leading to the loss of gingival connective tissue and alveolar bone. Lately, periodontal disease is considered as a co-morbidity of diabetes mellitus (Polak, Sanui et al., 2020). Though studies that have assessed the relationship of periodontal status with the glycemic control in type 1 diabetes mellitus adolescents, such studies have not been conducted in South Africa.

Introduction Patients with serious psychiatric disorders have an increased morbidity and mortality in somatic diseases and elevated prevalence of both diabetes and prediabetes. This increased frequency of somatic diseases is believed to be associated with life style choices and side effects of the antipsychotic medication. Aim In our study we investigated the prevalence of diabetes and prediabetes and compared metabolic risk factors and treatments between patients with and without serious psychiatric disorders in patients with diabetes in Region Örebro County (RÖC). Material and methods The prevalence of diabetes and prediabetes was determined in 944 patients identified from psychiatric outpatient clinics in RÖC. Information about risk factors and treatments were acquired by retrospective examination of medical records. Results Diabetes was identified in 113 patients and prediabetes in 42 patients. In patients with diabetes and serious psychiatric disorders men had significantly higher levels of HbA1c (p<0.01) and creatinine (p<0.01) compared to women, whereas women had higher BMI (p<0.05). No significant differences in HbA1c and BMI were found between patients with psychiatric disorders and all patients in RÖC with diabetes. Patients with psychiatric disorders did however have a significantly higher number of current smokers and a lower prescription of antihypertensive medication. Conclusions The prevalence of diabetes and prediabetes were 12.0% and 4.4%, respectively, in patients with serious psychiatric disorders. Our study indicates no difference in glycaemic control between psychiatric and non-psychiatric patients with diabetes, but there are differences in certain risk factors connected to diabetes.

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.

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.

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.

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.

Type 1 Diabetes is a dangerous and life-long disease for which its prevalence is global. Research has shown that tight glycaemic control of this disease significantly reduces the risks of developing several life threatening diabetic complications. The Ets-Insulin-Bolus Calculator (EIBC), inspired by the Ets concept (Equivalent Teaspoon Sugar), was primarily designed to assist type I diabetics in improving their blood glucose control. The EIBC has shown to improve the average blood glucose level of type 1 diabetics. The need for this study however is to determine whether the ET!3C promotes tighter glycaemic control for type 1 diabetics based on a more-in-depth numerical analysis. With the use of the latest technology in blood glucose monitoring, the CGMS from Medtronic, mathematical models expressing and rating blood glucose control have been proposed and derived in this study. A clinical trial with type 1 diabetics has also been conducted. The use of the models together with the clinical trial results have shown that the EIBC does in fact promote tighter glycaemic control for type 1 diabetics. / Thesis (M.Ing. (Mechanical Engineering))--North-West University, Potchefstroom Campus, 2007.