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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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.

HSV-2 may have adverse consequences in HIV. I evaluated the impact of HSV-2 co-infection on (highly active antiretroviral therapy)-untreated HIV infection in a systematic review of observational studies (study 1) and a retrospective cohort (study 2). I further evaluated whether HSV reactivation rates in co-infected persons differ by use of suppressive cART (study 3). Study 1 found modest evidence that HSV-2 seropositivity may be associated with accelerated progression to opportunistic infection or clinical AIDS, but not with increased HIV viral load. Some evidence suggests that HSV-2 disease activity is associated with increased HIV viral load and decreased CD4 counts. Study 2 compared rates of CD4 count change by HSV-2 status (Focus HerpeSelect ELISA) among 218 patients with a past period of ART-untreated follow-up using mixed linear regression models. No significant difference in the rate of CD4 count change was observed in HSV-2 seropositives at +13.6 cells/mm3/year (p=0.12) in univariate analysis, and -4.5 cells/mm3/year (p=0.68) in analysis adjusted for sex, HSV-1, oral and genital HSV symptoms, immigrant status, and immigrant*time interaction. These findings support the need for carefully designed and executed studies of HSV-2 suppression as an adjunctive management strategy for HIV disease, but raise questions regarding the exact mechanism of negative synergy between these viruses and the relative importance of HSV-2 latency and replication in driving these effects. In Study 3, 44 cART-naïve and 41 treated (HIV RNA<50 copies/mL) HIV+ adults with HSV-1 and/or 2 co-infection collected oral, genital and anal swabs daily for 28 days. Negative binomial models were used to quantify the relationship between cART and HSV shedding (Roche LightCycler HSV1/2). Overall HSV shedding was low, at a median (IQR) of 3.6% (0, 14.3%) of days. No relationship was seen between cART and HSV-1 or 2 shedding in univariate (RR=1.55, 95%CI=0.83,2.87) or multivariate analysis adjusted for sex, baseline CD4, recent immigrant status, and time since HIV diagnosis (aRR=1.05, 95%CI=0.43,2.58). Null results were also observed for HSV-1 and HSV-2 considered separately. That HSV shedding persists despite cART suggests that trials of anti-HSV drugs for improving HIV outcomes may be warranted in such patients.

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.

Proefschrift Maastricht. / Lit. opg. - Met samenvatting in het Nederlands.