Compared to other Canadians, Aboriginal people suffer disproportionately from Type 2 diabetes and its complications. In an attempt to fill gaps in services for Aboriginal people to support better management of diabetes and to prevent further complications, the West Side Community Clinic launched a monthly outreach diabetes education program using an informal hands-on approach to learning about meal planning and other forms of diabetes management. The purpose of this qualitative study was to determine the impact that the program has had on the participants' health and well-being through the stories they shared in a group or individual interview. Out of the core group of 30 women, most of them Aboriginal, eleven participated in the group interview and five women participated in individual interviews.<p>Findings reveal that the program's impact on participants' health and well-being is embedded within the context of their lives. Diabetes is managed within multiple life realities in an individual, a familial and a community context. The women report learning management skills and sharing support among participants and staff of Diabetes Morning; and altered health status such as regulated blood glucose levels and weight loss. Opportunities for change include more programming like Diabetes Morning, more often, more information, access to low-cost diabetes-friendly foods, communication with health care practitioners, and integrating knowledge on a day-to-day basis. Domains for outcome indicators and contextual indicators are suggested for the program.

Studies show that insulin induced activation and assembly of insulin receptor substrate-1 (IRS1) and phosphatidylinositol-3-kinase (PI3K), within remodelled actin structures is critical for GLUT4 translocation to the cell surface in muscle cells. This study identifies the F-actin binding protein, nexilin, as a novel IRS1 binding partner. Insulin stimulates nexilin to dissociate from IRS1 and interact with actin. Nexilin knockdown has no effect on insulin-stimulated IRS1 tyrosine phosphorylation, but does enhance insulin-stimulated IRS1-PI3K interaction, increasing PIP3 formation, PKB activation and glucose uptake. This study also shows that nexilin overexpression may have an inhibitory effect on PKB phosphorylation and glucose uptake in adipocytes. These findings suggest nexilin is a negative regulator of IRS1 action on PI3K and insulin-stimulated dissociation of IRS1-nexilin allows the formation of IRS1-PI3K complexes in cytoskeletal-membrane compartments. Nexilin also specifically associates with the PH domain of IRS1, and not IRS2, suggesting a mechanism for signaling specificity of these isoforms.

Studies show that insulin induced activation and assembly of insulin receptor substrate-1 (IRS1) and phosphatidylinositol-3-kinase (PI3K), within remodelled actin structures is critical for GLUT4 translocation to the cell surface in muscle cells. This study identifies the F-actin binding protein, nexilin, as a novel IRS1 binding partner. Insulin stimulates nexilin to dissociate from IRS1 and interact with actin. Nexilin knockdown has no effect on insulin-stimulated IRS1 tyrosine phosphorylation, but does enhance insulin-stimulated IRS1-PI3K interaction, increasing PIP3 formation, PKB activation and glucose uptake. This study also shows that nexilin overexpression may have an inhibitory effect on PKB phosphorylation and glucose uptake in adipocytes. These findings suggest nexilin is a negative regulator of IRS1 action on PI3K and insulin-stimulated dissociation of IRS1-nexilin allows the formation of IRS1-PI3K complexes in cytoskeletal-membrane compartments. Nexilin also specifically associates with the PH domain of IRS1, and not IRS2, suggesting a mechanism for signaling specificity of these isoforms.

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.

Compared to other Canadians, Aboriginal people suffer disproportionately from Type 2 diabetes and its complications. In an attempt to fill gaps in services for Aboriginal people to support better management of diabetes and to prevent further complications, the West Side Community Clinic launched a monthly outreach diabetes education program using an informal hands-on approach to learning about meal planning and other forms of diabetes management. The purpose of this qualitative study was to determine the impact that the program has had on the participants' health and well-being through the stories they shared in a group or individual interview. Out of the core group of 30 women, most of them Aboriginal, eleven participated in the group interview and five women participated in individual interviews.<p>Findings reveal that the program's impact on participants' health and well-being is embedded within the context of their lives. Diabetes is managed within multiple life realities in an individual, a familial and a community context. The women report learning management skills and sharing support among participants and staff of Diabetes Morning; and altered health status such as regulated blood glucose levels and weight loss. Opportunities for change include more programming like Diabetes Morning, more often, more information, access to low-cost diabetes-friendly foods, communication with health care practitioners, and integrating knowledge on a day-to-day basis. Domains for outcome indicators and contextual indicators are suggested for the program.

Adiposity has been shown to secrete bioactive cytokines and growth factor known as adipocytokines, they can contribute to obesity, diabetes and complications of diabetes. Visfatin is a novel adipocytokine, and it was shown to exert insulin-mimetic effects in stimulating glucose transport and induced triglyceride accumulation in preadipocytes and triglyceride synthesis from gluvose. Visfatin plasma levels are increased in morbid obesity and type 2 diabetes mellitus. These finding indicate that visfatin may play a role in the association between visceral obesity and increased metabolic risk, visfatin gene suggested that genetic variation in the visfatin gene may, indeed, have a minor effect on visceral and subcutaneous visfatin messenger RNA expression profiles and parameters of glucose and insulin metabolism. In this study, we explored the relationships between the plasma level of visfatin and genetic single nucleotide polymorphisms (SNPs) of visfatin gene in type 2 diabetes mellitus (T2DM) with and without macrovascular disease. Plasma visfatin was found to be elevated significantly in T2DM with macrovascular disease patients. Moreover, waist to hip ratio was independently associated with plasma visfatin level. There were statistically significant differences in visfatin -948 G/T genetic variants distribution between T2DM with macrovascular disease and the T2DM control group. The visfatin -948 G/T heterozygotes showed higher mean high-density lipoprotein cholesterol than the carriers of the G allele. The results of the current study indicated that plasma visfatin levels were associated with macrovascular complications in type 2 diabetes. However, the definite roles of visfatin in the pathogenesis of insulin resistance, glucose and lipid metabolism are unclear. The observation of changes in the plasma concentrations of visfatin seen in T2DM and T2DM with macrovascular diseases may exert beneficial effects in understanding roles of visfatin in physiologic activity and metabolic disorder. Further studies are needed to elucidate the mechanisms behind visfatin overexpression in humans.

Statement of Problem: Aboriginal youth are at greater risk of Type 2 Diabetes (T2D) compared to non-Aboriginal youth. Diabetes prevention strategies need to consider cultural factors that are embedded within an ecological perspective. Methods: Photovoice was used to explore the meanings of T2D and the Aboriginal Youth Mentorship Program (AYMP). Also, a non-randomized crossover experimental trial was performed on children. Grade 4 students were offered a 5 month intervention led by high school mentors. The main outcome measures were WC and BMI z score. Results: Results indicate that youth were very hopeful that T2D can be prevented or managed through nutrition and physical activity. They believe that AYMP can help with T2D prevention, through learning positive health behaviors, but also by enhancing social determinants of health related to education, employment and social support networks. After the intervention, the change in WC was significantly lower in the intervention group compared to the control group (p <0.05). Conclusion: Findings from this research study show that AYMP may be a successful program in teaching positive lifestyle behaviors while supporting social determinants of health; the combined biological and social outcomes can benefit students in reducing their risk for T2D. / October 2015

Aims: Elders with type 2 diabetes represent the faster growing demographic segment today, yet there is little known about the factors that influence their diabetes self care management. The factors (age related developmental deficits, health literacy, knowledge of diabetes as a disease, and prior attendance within a structured diabetes educational program) that most impact diabetes self care among this age group was determined from the literature. Seven research questions and three model hypothesis questions were posed to examine the relationships between these identified factors. Method: The study was composed of 75 elders with type 2 diabetes who resided within two metropolitan regions in the Southwest. The elders were asked to perform manual dexterity tests, visual acuity examination, and tests of cognition along with answering questions in regard to their health literacy and knowledge of diabetes. Results: Of all the factors examined only health literacy and cognitive reasoning ability were statistically significant to the measure of diabetes self care.

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.

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