Type 2 diabetes (T2DM) is a chronic disease characterized by cellular insulin resistance and consequent disturbances in glucose metabolism. Long-term consumption of buckwheat has been previously shown to improve glycemia in individuals with T2DM; however, the underlying mechanisms as well as the contribution of improved acute glycemic responses have not been fully characterized. The current study used cell culture and clinical studies to investigate the mechanisms and effectiveness of common buckwheat for acute modulation of glucose metabolism and glycemia. Glucose uptake was inhibited in H4IIE cells treated with a buckwheat extract (BWE), an effect attributed to the actions of an unknown compound(s). Reduced glucose uptake and transepithelial glucose transport was also present in Caco2 colorectal adenocarcinoma cells and monolayers. The mechanism behind inhibited glucose uptake did not involve modulation of several signaling pathways regulating glucose metabolism, including p38 MAPK, p42/44 ERK, PI3Kγ, PKC, PKA, mTOR and AMPK. Interestingly, BWE treatment was associated with other effects on glucose metabolism, including elevated glucose production and levels of gluconeogenic enzymes. However, these effects were not mediated through the classical pathway of CREB activation involving cyclic AMP and PKA. In a blinded, reference product-controlled study, consumption of a cracker product made from whole grain common buckwheat flour containing 50 grams of available carbohydrate was not associated with changes in post-prandial glucose or insulin concentrations in both healthy individuals and those with diet-controlled T2DM. However, consumption of buckwheat crackers was associated with changes in selected gastrointestinal satiety hormones. Interestingly, several significant correlations observed between fasting concentrations and the overall post-prandial response of these hormones were affected by T2DM. In conclusion, glucose-lowering effects of common buckwheat are not due to the actions of known bioactive compounds, and may involve direct inhibition of facilitative transporters by a novel compound. Although a buckwheat food product did not reduce post-prandial glycemia, identifying the compound responsible for inhibited glucose uptake will allow development of food products enriched with this compound, and may represent a more effective dietary approach to managing glycemia.

The goal of this study was to compare different anthropometric measures in terms of their ability to predict T2DM and to determine whether predictive ability was modified by ethnicity. Anthropometrics were measured at baseline on 1073 non-Hispanic Whites (nHW), African Americans (AA) and Hispanics (HA), of which 146 developed T2DM after 5.2 years. Logistic regression models were used with areas under the receiver operator characteristic curve (AROC) comparing the prediction of models. Overall, there was no clear distinction between measures of overall and central obesity in terms of T2DM prediction. Waist-height ratio (AROC=0.678) was the most predictive measure, followed by BMI (AROC=0.674). Results were similar in nHW and HA, although, in AA, central adiposity measures best predicted T2DM. Measures of central and overall adiposity predicted T2DM to a similar degree, except in AA where central measures were most predictive.

The goal of this study was to compare different anthropometric measures in terms of their ability to predict T2DM and to determine whether predictive ability was modified by ethnicity. Anthropometrics were measured at baseline on 1073 non-Hispanic Whites (nHW), African Americans (AA) and Hispanics (HA), of which 146 developed T2DM after 5.2 years. Logistic regression models were used with areas under the receiver operator characteristic curve (AROC) comparing the prediction of models. Overall, there was no clear distinction between measures of overall and central obesity in terms of T2DM prediction. Waist-height ratio (AROC=0.678) was the most predictive measure, followed by BMI (AROC=0.674). Results were similar in nHW and HA, although, in AA, central adiposity measures best predicted T2DM. Measures of central and overall adiposity predicted T2DM to a similar degree, except in AA where central measures were most predictive.

Purpose: The prevalence of diabetes (DM) is increasing globally with type 2 diabetes (T2DM) being primarily responsible for this alarming trend. Age and DM have been associated with an increased prevalence of AR cataract in earlier studies but T2DM has not been considered separately from type 1 diabetes. Furthermore, study results have been inconsistent in terms of whether nuclear sclerosis (NS), cortical cataract (CC) or posterior subcapsular (PSC) are specifically associated with DM. The purpose of this thesis was to provide Canadian data on these issues while considering the limitations found in earlier studies in terms of variable age group selection and cataract definition. Logistic regression analysis was extended beyond risk analysis to model the prevalence of AR cataract across the human age range. Finally, as statins are commonly prescribed for patients with T2DM, the impact of using this pharmaceutical on AR cataract prevalence was investigated. Methods: A file review of over 6397 clinic files was performed to create the Waterloo Eye Study (WatES) database. Abstracted data included patient age and sex, the presence of early to late AR cataract (NS, CC, PSC or related lens extraction-LE), systemic health diagnoses including a diagnosis of T2DM or type 1 diabetes, and any medication used. Data quality was looked at through repeatability with double-entry of files and calculation of missing data rates. Comparisons were done between the study population demographics (age and sex) and those available on the general population and representative Canadian optometric patients. Prevalence of AR cataract was determined for the entire study group and for yearly age-groups. The probability of AR cataract generated from logistic regression analysis was used to model the prevalence of AR cataract over the entire age range of patients. Similar functions were determined for T2DM and non-diabetic (ND) subgroups and then again after further subdividing them into patients who did and did not use statins. The age of 50% prevalence of AR cataract were determined for each of these functions. Distribution rates of mixed and uniform cataract were calculated and compared for the T2DM and ND subgroups. Age of first lens extraction and differences in LE rates were also determined for these groups. Multivariable logistic regression analysis was done to determine odds ratios (OR) for associations between variables (patient age, being female, having a diagnosis of T2DM, smoking, systemic hypertension, and statin use) and the outcome of AR cataracts or its subtypes. Results: Data abstraction repeatability was found to be high and missing data rates were found to be low. While significant differences existed between the demographics of the general population and this clinic population, the sex and age distributions were comparable to optometric practices in Canada. The overall prevalence of AR cataract, NS, CC,and PSC in this population was 35.3%, 28.8%, 9.9%, and 3.6% respectively. The yearly prevalence of AR cataract in this population was found to increase in a sigmoid trend over the course of the human age span that began to rise after 38 years of age and approached 100% by 75 years of age. When modelled into a probability of cataract function, 50% prevalence of AR cataract occurred at 56.6 years of age. T2DM was reported in 452 WatES patients; 97% of whom were over 38 years of age. The probability of 50% AR cataract, NS, and CC prevalence occurred almost four years earlier in the T2DM subgroup compared to those without diabetes. PSC was much less prevalent and did not reach 50% levels, but the age of 10% prevalence was eight year earlier in the T2DM group compared to the ND group. Patients with T2DM had more mixed cataract, a higher rate of LE and an earlier age of first LE than non-diabetics. Statin use was reported in 761 patients; 96% who were over 38 years of age. Statin use was 3.5 times more common in patients with T2DM compared to non-diabetics. When the diabetic subgroups were further subdivided by those who do and do not use statins, the age of 50% probability of AR cataracts was now almost eight years earlier in the T2DM patients using statins compared to the ND patients who did not. The probability functions were similar between T2DM patients not using statins and ND patients who did report statin use. Having a diagnosis of T2DM was significantly associated with early to late NS and CC when controlling for statin use, whereas statin use was significantly associated with NS and PSC when controlling for a diagnosis of T2DM. Conclusions: AR cataract, T2DM and statin use were prevalent conditions in this clinic population, especially over 38 years of age. Modelling the prevalence of AR cataract over a broad age range could assist predicting cataract in Canadian optometric patients. A diagnosis of T2DM resulted in an earlier development of all three cataract subtypes, resulting in increased rates of LE and mixed cataract. However, the association was only significant for NS and CC when controlling for statin use. Given the frequent use of statins in patients with T2DM, the significant association found between statin use and increased risk of AR cataract warrants further study.

Interest in the ketogenic diet and its potential to treat obesity and type 2 diabetes has been steadily growing in recent years. With a very limited amount of calories coming from carbohydrates (typically < 50 gm/day), and the majority of calories coming from fat, this diet leads to a states of physiological ketosis, in which ketone bodies replace glucose as the primary source of energy. Early clinical trials found this to lead to a spontaneous reduction in calories consumed, and it has been suggested that a state of ketosis has appetite suppressing properties. There are a few studies evaluating self-reported decrease in hunger while consuming a ketogenic diet, as well as the changes in hormone levels associated with appetite, but this evidence is limited. The primary determinant of weight change is the difference between calories consumed and calories burned, however there is some suggestion that the macronutrient composition of the ketogenic diet may have a specific metabolic advantage for weight loss separate from the total number of calories in deficit. Multiple diet comparison studies have found the ketogenic diet to be effective for weight loss in the short term, particularly when compared to low fat diets. It is questionable whether the ketogenic diet is sustainable in the long term, particularly without frequent nutritional counseling and monitoring. Still, there is preliminary evidence that the ketogenic diet can lead not only to a large amount of weight loss, but may also be effective in treating and reversing type 2 diabetes. Clinical trials have shown decreases in HbA1c, fasting glucose, and reduction of antiglycemic medication requirements, though it is unclear if these effects are primarily due to weight loss itself, or the specific composition of the ketogenic diet. These benefits need to be weighed against the risks, and a common criticism is its high fat content which can adversely affect serum lipid levels and thus risk of cardiovascular disease. Consuming a ketogenic diet with a high intake of saturated fat has been found to increase LDL cholesterol, however this effect can be mitigated by favoring polyunsaturated or monounsaturated fats instead. While the above findings provide a preliminary understanding of the effects of the ketogenic diet, more research is needed to further elucidate the effectiveness and safety of the diet for treating obesity and type 2 diabetes.

The prevalence of overweight and obesity in adolescents has increased dramatically over the past few decades. This increase is associated with a higher risk of developing Type 2 Diabetes Mellitus (T2DM). The "R.U.A. Healthy Kid?" program was created to target modifiable risk factors related to development of T2DM. This study specifically focuses on the influence of snacking habits. Researchers have documented an increase in snacking occasions and preference for low-nutrient snacks among adolescents. Many adolescent diabetes prevention programs target dietary behaviors, but none have used the Stages of Change as a theoretical framework to promote behavior change. The purpose of this study was to determine the impact of a three month community-based intervention on snack consumption and snacking habits of adolescents with risk factors for T2DM. Additionally, it explored the use of the Stages of Change model to understand how the intervention impacted adolescents' movement through the stages, and if reported stage was related to reported snack consumption and snacking habits. At completion of the study, the majority of participants reported forward progress in stages of change, indicating they were actively making changes in regards to high-nutrient (healthy) snacking. There was also a decrease in low-nutrient (unhealthy) snack consumption, and a significant improvement in overall snacking score. Participants reported several factors influenced their snack choice including hunger, taste, and availability. These findings are important to the development of appropriate programs to encourage healthy dietary behaviors at a young age.

In the past 30 years the prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus (T2DM) and other co-morbidities. Visceral adipose tissue is believed to play a vital role in these conditions, but underlying mechanisms remain unclear. A close association exists between obesity, diabetes and oxidative stress, resulting in increased reactive oxygen species formation. The experiments in this thesis address this by searching for possible biochemical changes which may be specific for the onset of obesity related T2DM, as well as looking for genetic alterations at molecular and gene expression levels. This thesis also explored various techniques such as polymerase chain reaction (PCR), colorimetric assays and real-time RT-PCR. The aim was to investigate the role of adipose tissue in obesity and T2DM, focusing on markers of oxidative stress and gene expression in human visceral adipose tissue from subjects categorised as lean, obese and obese with T2DM. This cross-sectional study measured two markers of oxidative stress, two markers of DNA damage, gene expression analysis and identification of genes associated with T2DM and obesity. Specific gene sequencing was carried out on the glutathione reductase gene to determine possible gene variants. Results showed a paradoxical decrease in adipose markers of oxidative stress in subjects with obesity and T2DM. There appeared to be a protective mechanism in these subjects, displaying reduced levels of oxidative stress compared to other groups. This could be due to a significant proportion of these subjects being on ACE inhibitor and statin therapy, which may be confounding results and minimising the effects of the oxidative burden. Additionally, the same subjects showed an increased expression of the glutathione reductase gene. It is difficult to conclude if the decreased levels of oxidative stress in these subjects were a result of the increased glutathione reductase expression in the visceral adipose tissue or if there remains an unseen factor influencing the dramatic expression change seen in this group of subjects. No glutathione reductase gene variants were identified in these samples. This analysis highlighted that within this sample set, the impact of oxidative stress is in fact reversible as the antioxidant capacity in these subjects is evident, and in combination with correct drug therapy it may be possible to combat oxidative burden and reduce the subsequent damage inflicted upon the cells.

Thesis submitted in fulfilment of the requirements for the degree Masters of Technology: Radiography in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology / BACKGROUND: Diabetic patients are at increased risk of cardiovascular events and stroke, and its prevention is therefore the desired goal. In the arsenal of available techniques, ultrasound plays a vital role in primary healthcare. It is reliable, cost-effective and a noninvasive diagnostic tool that may prove beneficial for screening individuals at risk of cardiovascular disease (CVD) and stroke in SA. OBJECTIVE: To determine the interrelationships between carotid ultrasound findings with glycaemia status and contributing risk factors of atherosclerosis in the selected population. METHODS: Initially blinded by the glycaemia status, blood results, contributing risks and patient demographics, both carotid arteries were evaluated with duplex ultrasound (DUS), during July 2010 – July 2011. Using graphs, figures, frequency tables, means and standard deviations for the selected study population, univariate, multivariate and stepwise regression analysis was done to determine the association between ultrasound findings and risk factors for atherosclerosis. The hypothesis tested in this study was to determine if there is an increased incidence of carotid artery intima-media thickening (CIMT), plaque formation and stenosis in patients diagnosed with T2DM and hyperglycaemia in a very specific sub-population of mixedancestory, residing in Bellville South Africa (BSA). RESULTS: Of 534 subjects, 375 were of mixed ancestry and ≥35yrs of age, which met the inclusion criteria for the carotid ultrasound substudy. The glycaemic status for each individual was established, and 44% (165/375) were diagnosed hyperglycaemic, of which 66.7% (110/165) were diabetic (T2DM) and 33.3% (55/165) were pre-diabetic (Pre-DM). Majority (56%:265/375) had a normal glycaemic status. The ultrasound measurement of the carotid wall thicknesses (Mean Rt. and Lt. CIMT) revealed a statistically significant rise from normal glycaemia status to DM status for both the males (p = 0.0115*; p = 0.0259*) and females (p < 0.0001**; p < 0.0001**) respectively. In terms of plaques and internal carotid artery (ICA) stenosis (124/375), when grouped into normal and hyperglycaemic sub-groups, indicated plaque presence and some form of narrowing. A <50% stenotic ratio noted in 61% (76/124) of the hyperglycaemic group, that was 1.6 times higher than those with normal glycaemia (48/124). Predisposing factors demonstrated significantly higher levels in the females than in the males. The univariate multiple regression analysis after adjusted R² of 0.3247 for all independent variables (predisposing /contributing risk factor markers) of age (yrs.), SBP (mmHg), hs-CRP (mg/L), S-Cotinine (ng/mL) and LDL (mmol/L) showed statistically significant positive associations with dependent variable of the mean carotid wall thickness (p < 0.0001**, p< 0.0001**, p = 0.0033*, p = 0.0409* and p = 0.0044)* respectively. Statistically significant positive differences and standard error (SE), for every unit of change (1yr.) of age (yrs.), as a contributing factor for herosclerosis, there was a change in the mean carotid wall thickness as predicted according to this model. The total contribution of independent risk factors to CIMT ultrasound measurements were calculated as 34.5% (Adjusted R² = 0.3247). In the multivariate stepwise regression analysis, the independent variables of age (p< 0.0001) ** and systolic blood pressure (p < 0.0001) ** showed the strongest positive association with carotid wall thickeness changes. The hs-CRP (mg/L) inflammatory markers (p = 0.0014)* and LDL (mmol/L) (p = 0.0208)* were the 2nd and 3rd highest positive associated contributory risk factors for carotid artery wall thickening. The hip circumference (p = 0.0008)* and waist circumference (p = 0.0 555) + risk factors related to obesity was significant and approached significance, respectively, with the predicted increase of carotid artery wall thickening. CONCLUSION: Subjects diagnosed with T2DM and hyperglycaemia had increased levels of CIMT, plaques and carotid artery stenosis, compared to those subjects without T2DM. Age and systolic blood pressure, inflammatory (raised hs-CRP) and LDL cholesterol changes, and central (truncal) waist circumference adiposity, were positively associated with increased carotid intima media thickness. Smoking (S-Cotinine) and gender also reflected a direct relationship with CIMT changes. The hip circumference adiposity and diastolic blood pressure measurements were not directly associated with an increase in CIMT, which are in keeping with hypertension and obesity formulas. These findings confirm the association of thickened CIMT, plaques and stenosis with ‘unhealthy’ T2DM subjects at higher risk of CVD and stroke. The total contribution of independent risk factors to CIMT measurements were calculated as 34.5% (Adjusted R² =0.3247). The gathered information, discussion of results, and concluding statements thereby supports the recommendation of carotid artery ultrasound evaluation, for screening and diagnosis in primary health care, for ‘flagging’ high risk individuals at risk of stroke, so that lifestyle changes and appropriate management is early adopted.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Revisión por pares / INTRODUCCIÓN: Los pacientes con diabetes mellitus tipo 2 son más propensos a una baja calidad de vida, discapacidad e incluso muerte. También, tienen una mayor predisposición a la depresión en comparación con los pacientes no diabéticos; así como una evolución favorable producto de la evaluación e intervención de su salud mental. OBJETIVOS: El objetivo de este estudio fue explorar la presencia de síntomas depresivos en una población ambulatoria con diagnóstico de diabetes mellitus tipo 2 y filiación militar. También examinar los factores asociados a la presencia de síntomas depresivos. MÉTODOS: Realizamos un estudio transversal en 108 personas con diabetes mellitus tipo 2, durante enero de 2012 en una muestra ambulatoria de un hospital de las fuerzas armadas. Los síntomas depresivos se evaluaron con el test autoaplicado de Zung. Usamos la prueba de Chi-cuadrado para examinar las asociaciones entre síntomas depresivos y los factores asociados de interés. Usamos modelos lineales generalizados crudos y ajustados para estimar las Razones de Prevalencia (RP) de la asociación entre las características clínicas y sociodemográficas con la presencia de síntomas depresivos. RESULTADOS: La prevalencia de sintomatología depresiva fue de 56,5% (intervalo de confianza 95%: 46,6-66,0%). El análisis bivariado mostró como significativa la asociación entre la presencia de síntomas depresivos con las variables: sexo, edad y complicaciones clínicas de la diabetes. En los análisis ajustados, la retinopatía diabética [RP: 1,3; intervalo de confianza 95%: 1,1-1,7], y la neuropatía diabética [RP: 1,4; intervalo de confianza 95%: 1,1-1,7] se asociaron a una mayor presencia de síntomas depresivos luego de considerar el sexo de los participantes. CONCLUSIONES: Observamos una elevada presencia de síntomas depresivos en la población de estudio, especialmente en los pacientes geriátricos o del sexo femenino. También en aquellos con complicaciones tardías de la diabetes mellitus tipo 2, y que probablemente representen la repercusión de la enfermedad en la calidad de vida del paciente. Un abordaje multidisciplinario, con enfoque físico y mental, debe ser considerado ya que podría beneficiar a la evolución de los pacientes con esta concomitancia en Perú.

Diabetes is a chronic, complex illness with a risk for acute and long-term complications. The aim of this quality improvement project on prevention of type 2 diabetes was to increase self-management behaviors in patients at high risk of type 2 diabetes, decrease the financial burden of type 2 diabetes, and decrease the incidence of complications that can occur from type 2 diabetes. The primary outcome of this project was each participant reporting at least one lifestyle modification that would be helpful in preventing type 2 diabetes after attending two group education sessions. A pretest posttest design was used for this project. Three completed the initial questionnaires, and two attended the educational sessions and completed the posttest questionnaires. Of the total number of participants, one reported a decrease in hot/cold cereal, regular soda, sugar or honey in coffee/tea, other potatoes, tomato sauces, chocolate, doughnuts, and cookies, cake, pies, brownies. Two participants reported a decrease in fruit juice, fried potatoes, and pizza. One participant had an increase in physical activity while the other participant had no change in physical activity. The landmark Diabetes Prevention Program (DPP) Trial demonstrated that counseling on a healthy diet and moderate physical activity reduced the incidence of type 2 diabetes. The two participants in this project reported they made some helpful changes in diet after two education sessions. It is vital to the success of a prevention program to convey the significance of preventing a chronic disease such as type 2 diabetes