Thesis (Ph.D. (Dietetics))--North-West University, Potchefstroom Campus, 2010.

Background Due to population growth, aging, urbanisation, increasing prevalence of obesity and physical inactivity, diabetes mellitus (DM) has become one of the most important and prevalent chronic diseases. Glycated haemoglobin A1c (HbA1c) assessment is currently being used all over to monitor glycaemic control as a cornerstone of diabetes care. It might also be a useful screening tool for non–insulin dependent DM, also known as type 2 DM (T2DM). Elevated HbA1c can be linked with long–term risk of cardiovascular complications. Aim The aim of the study was to determine whether HbA1c can be used as reliable screening tool for early detection of T2DM in an African population. Methods This study was a cross–sectional study and was part of the South African, North–West Province (SANWP) leg of the 12–year Prospective Urban and Rural Epidemiological (PURE) study. Baseline data was collected from March to December 2005. A total of 2010 volunteers were recruited from randomly selected households. Data was collected on socio–demographic characteristics, physical activity, dietary intakes, blood pressure and anthropometry. HbA1c, fasting plasma glucose (FPG), liver enzymes and HIV status were determined. Ethical approval for the PURE study was obtained in July 2004. Oral glucose tolerance tests (OGTT) were also done for a sub–group of 465 subjects. The Statistical Consultation Services of the North–West University were consulted to analyse data with SPSS 17.0 and STATISTICA 9.0. Results The HbA1c values within the diabetic FPG groups were 7.46% for men and 8.08% for women. HbA1c values increased significantly progressively from the normal FPG groups to the groups with impaired FPG and the diabetic FPG groups for both men and women. No significant increases were found in HbA1c between the OGTT groups (normal 2 hour plasma glucose (PG), impaired 2–hour PG and diabetic 2–hour PG). Total cholesterol, triglycerides, body mass index and FPG increased significantly and high–density lipoprotein cholesterol decreased significantly with an increase in HbA1c values in men and women. In addition, systolic blood pressure increased significantly in women with increased HbA1c. Thus, with an increase in HbA1c, an increase in the number of risk factors was observed. When using HbA1c and FPG in combination, 43 subjects of the whole population were detected with having a risk of developing T2DM. However, when considering the commonality of subjects identified to be diabetic or at risk by the OGTT, FPG and HbA1c individually, only one subject was identified by all the methods as having diabetes or being at risk to develop diabetes. Discussion and conclusions An increase in HbA1c and FPG was associated with an increase in risk factors and therefore with metabolic syndrome (MS). MS is associated with an increased risk of developing T2DM and therefore it can be concluded that HbA1c was useful for detecting in this population individuals at increased risk of developing T2DM. The use of FPG and HbA1c in combination was considered a better screening tool when compared to HbA1c alone. Factors other than what were measured in this study might be the cause of the unexpected results obtained in the participants with impaired OGTT. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2011.

Bakgrund: Av befolkningen i Sverige 9,7 miljoner är fyra till sex procent drabbade av diabetes. Nästan nittio procent av dessa personer har diabetes typ två. I omvårdnadsprocessen ingår undervisning och att förmedla information som en del av sjuksköterskans arbete. För att omvårdnaden av diabetes som syftar till att stabilisera HbA1c skall uppnå goda resultat, krävs en förändrad livsstil. Forskning har visat att mötet med sjuksköterskan har betydelse för att personen skall kunna förändra sin livsstil. Syfte: var att beskriva personer med diabetes typ två upplevelse av mötet med sjuksköterskan. Metod: Studien genomfördes som en allmän litteraturstudie som baserades på femton kvalitativa artiklar. Analysen genomfördes med inspiration av Friberg (2012). Resultat: presenteras i tre kategorier med subkategorier: upplevelsen av det första mötet, upplevelsen av information i mötet, upplevelsen av sjuksköterskans undervisning i mötet. De viktiga faktorerna i mötet som framkom var; samarbete, kontinuitet, delaktighet, undervisning och individuell information. Diskussion: Tre delar som diskuterades var; faktorer i det första mötet som främjade att en relation utvecklades, betydelsen av att få individuell information och betydelsen av sjuksköterskans undervisning. Slutsats: Det finns ett behov av att belysa hur personer upplever mötet med sjuksköterskan. Genom att sjuksköterskan utbildas att ge personer stöd och individuellt anpassad information och undervisning kan det leda till en förbättrad egenvård. / Background: Of the population in Sweden 9.7 million are four to six percent injured by diabetes. Almost ninety percent of these persons have diabetes type two. In the nursing process includes support as a part of the nurse's work. In the nursing process includes education and to convey information as a part of the nurse's work. The goal with the care of diabetes is to stabilize HbA1c and to achieve good results is it necessary to change lifestyle. Research has shown that the meeting with the nurse is important for the person to be able to change their lifestyle. Aim: The aim was to describe people with diabetes type two experience of meeting with the nurse. Methods: The study was conducted as a literature study based on fifteen qualitative articles. The analysis was performed with the inspiration of Friberg (2012). Results: Presented in three categories with subcategories: the experience of the first meeting, the experience of information in the meeting, the experience of the nurse's teaching in the meeting. The important factors in the meeting that emerged were: cooperation, continuity, participation, education and individual information. Discussion: Three sections that were discussed; factors in the first meeting that promoted a relationship developed, the importance of getting individual information and the role of the nurse's teaching. Conclusion: There is a need to describe how people experience the meeting with the nurse. If the nurse are trained to give persons support and individual information and education can it lead to a better self-care.

To accurately predict the outcome of a late phase study, pharmacometric models can help in drug development. Making informed decision on which models to use will also facilitate drug development. This can depend on the mechanism of action for the drug as well as stability and runtime factors. This is an investigation of four published semi-mechanistic pharmacometric models to predict glycosylated red blood cells (HbA1c) in a late phase study of an anti-diabetic drug together with an assessment of their stability and power to detect drug effects. Mean plasma glucose (MPG), fasting plasma glucose (FPG) or FPG and fasting serum insulin (FSI) are used together with HbA1c as drivers for change in the models. We find that less complex models, with fewer differential equations, are quicker to run and more stable, and that MPG alone is superior to FPG or FPG and FSI to detect a drug effect. The findings are useful for drug development in the anti-diabetic area, and show that a less mechanistic model performs well under these conditions.

Emerging evidence suggests that vitamin D may be associated with type 2 diabetes (T2DM), however current data are inconsistent regarding metabolic disorders underlying T2DM. The objectives of this thesis were to investigate the association of vitamin D with the primary pathophysiological disorders of type 2 diabetes: namely insulin resistance (IR) and beta (β)-cell dysfunction, and the metabolic syndrome (MetS). All studies included individuals participating in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, comprising 712 subjects 30 years and older, and at risk of T2DM at baseline. Serum 25-hydroxyvitamin D [25(OH)D] was measured to assess vitamin D nutritional status. Validated oral glucose tolerance test derived indices for IR and β-cell function were calculated. In the first cross-sectional study, multivariate linear regression analyses indicated a significant inverse association of serum 25(OH)D with IR (β=-0.003, p=0.007) and a significant positive association of 25(OH)D with β-cell function (β=0.004, p=0.03) at the baseline PROMISE clinic visit (n=712). In another cross-sectional study also conducted using data from the baseline PROMISE clinic visit, higher 25(OH)D was found to be significantly associated with a reduced presence of the MetS after multivariate adjustment (OR=0.76, 95% CI 0.62-0.93). Low serum 25(OH)D was also significantly associated with various MetS components. In light of the findings in the first cross-sectional study, the third study examined prospective associations of baseline 25(OH)D with 3-year follow-up IR and β-cell function (n=489). Although baseline 25(OH)D was not significantly associated with follow-up IR, a significant positive association of baseline 25(OH)D with β-cell function at follow-up was observed (β=0.005, p=0.015). Lastly, in a longitudinal substudy (n=127), seasonal changes in 25(OH)D over 2.5 years did not significantly affect changes in IR and β-cell function. In conclusion, results indicated that baseline serum 25(OH)D was cross-sectionally related to IR, β-cell function and the MetS, and was prospectively related to β-cell function at the 3-year follow-up. In addition, seasonal changes in 25(OH)D do not adversely affect IR and β-cell function over time. These findings suggest a potential role for higher 25(OH)D levels in reducing diabetes risk, although additional longitudinal studies are warranted.

Coffee consumption has consistently been associated with a reduction in risk of type 2 diabetes mellitus (T2DM), although the mechanism for this association remains unknown. Sub-clinical inflammation, non-alcoholic fatty liver disease (NAFLD), and lipoprotein abnormalities characterize and predict T2DM. Limited evidence suggests that coffee may have a beneficial role in these disorders but further investigation is warranted. Our aim therefore was to investigate the associations of caffeinated and decaffeinated coffee with markers of inflammation, liver injury, and lipoproteins, in a non-diabetic cohort. No significant associations of caffeinated or decaffeinated coffee with inflammatory markers or lipoproteins were identified. Caffeinated coffee consumption however was inversely associated with alanine aminotransferase (β= -0.09, p= 0.0107) and aspartate aminotransferase (β= -0.05, p= 0.0161) in multivariate analysis. Decaffeinated coffee was not associated with liver enzymes. These analyses suggest that caffeinated coffee’s beneficial impact on NAFLD may be a potential mechanism for its inverse association with T2DM.

Obesity is an adverse factor in the development and severity of breast cancer. Obesity is often accompanied by an increase in circulating insulin, which is also associated with poor BC prognosis. Although not expressed in normal breast tissue, the insulin receptor (IR) is highly expressed in BC, therefore insulin signaling in BC cells may be responsible for the negative prognostic effects associated with hyperinsulinemia. This thesis describes the development of a cell-based system to study how insulin affects BC. My work shows that MCF10A, untransformed human breast epithelial cells that express the IR, require insulin for normal proliferation and morphology. Interestingly, I discovered hyperactivation of ERK1/2 in MCF10A cells in response to insulin withdrawal, resulting in a loss of epithelial phenotype. Unexpectedly, while losing epithelial phenotype, MCF10A cells depleted of insulin failed to migrate. In conclusion, breast cells that express IR require insulin for migration and maintenance of epithelial characteristics.

Emerging evidence suggests that vitamin D may be associated with type 2 diabetes (T2DM), however current data are inconsistent regarding metabolic disorders underlying T2DM. The objectives of this thesis were to investigate the association of vitamin D with the primary pathophysiological disorders of type 2 diabetes: namely insulin resistance (IR) and beta (β)-cell dysfunction, and the metabolic syndrome (MetS). All studies included individuals participating in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, comprising 712 subjects 30 years and older, and at risk of T2DM at baseline. Serum 25-hydroxyvitamin D [25(OH)D] was measured to assess vitamin D nutritional status. Validated oral glucose tolerance test derived indices for IR and β-cell function were calculated. In the first cross-sectional study, multivariate linear regression analyses indicated a significant inverse association of serum 25(OH)D with IR (β=-0.003, p=0.007) and a significant positive association of 25(OH)D with β-cell function (β=0.004, p=0.03) at the baseline PROMISE clinic visit (n=712). In another cross-sectional study also conducted using data from the baseline PROMISE clinic visit, higher 25(OH)D was found to be significantly associated with a reduced presence of the MetS after multivariate adjustment (OR=0.76, 95% CI 0.62-0.93). Low serum 25(OH)D was also significantly associated with various MetS components. In light of the findings in the first cross-sectional study, the third study examined prospective associations of baseline 25(OH)D with 3-year follow-up IR and β-cell function (n=489). Although baseline 25(OH)D was not significantly associated with follow-up IR, a significant positive association of baseline 25(OH)D with β-cell function at follow-up was observed (β=0.005, p=0.015). Lastly, in a longitudinal substudy (n=127), seasonal changes in 25(OH)D over 2.5 years did not significantly affect changes in IR and β-cell function. In conclusion, results indicated that baseline serum 25(OH)D was cross-sectionally related to IR, β-cell function and the MetS, and was prospectively related to β-cell function at the 3-year follow-up. In addition, seasonal changes in 25(OH)D do not adversely affect IR and β-cell function over time. These findings suggest a potential role for higher 25(OH)D levels in reducing diabetes risk, although additional longitudinal studies are warranted.

Coffee consumption has consistently been associated with a reduction in risk of type 2 diabetes mellitus (T2DM), although the mechanism for this association remains unknown. Sub-clinical inflammation, non-alcoholic fatty liver disease (NAFLD), and lipoprotein abnormalities characterize and predict T2DM. Limited evidence suggests that coffee may have a beneficial role in these disorders but further investigation is warranted. Our aim therefore was to investigate the associations of caffeinated and decaffeinated coffee with markers of inflammation, liver injury, and lipoproteins, in a non-diabetic cohort. No significant associations of caffeinated or decaffeinated coffee with inflammatory markers or lipoproteins were identified. Caffeinated coffee consumption however was inversely associated with alanine aminotransferase (β= -0.09, p= 0.0107) and aspartate aminotransferase (β= -0.05, p= 0.0161) in multivariate analysis. Decaffeinated coffee was not associated with liver enzymes. These analyses suggest that caffeinated coffee’s beneficial impact on NAFLD may be a potential mechanism for its inverse association with T2DM.

Obesity is an adverse factor in the development and severity of breast cancer. Obesity is often accompanied by an increase in circulating insulin, which is also associated with poor BC prognosis. Although not expressed in normal breast tissue, the insulin receptor (IR) is highly expressed in BC, therefore insulin signaling in BC cells may be responsible for the negative prognostic effects associated with hyperinsulinemia. This thesis describes the development of a cell-based system to study how insulin affects BC. My work shows that MCF10A, untransformed human breast epithelial cells that express the IR, require insulin for normal proliferation and morphology. Interestingly, I discovered hyperactivation of ERK1/2 in MCF10A cells in response to insulin withdrawal, resulting in a loss of epithelial phenotype. Unexpectedly, while losing epithelial phenotype, MCF10A cells depleted of insulin failed to migrate. In conclusion, breast cells that express IR require insulin for migration and maintenance of epithelial characteristics.