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The protein Poly was first discovered in Drosophila melanogaster, during a screening for third chromosome lethal mutations. Drosophila poly mutant larvae exhibit a slower rate of development. However, they reach the third instar larval stage and remain at that stage for 21 days before they die without reaching pupation. This phenotype is attributed to developmental impairment of the imaginal discs, therefore suggesting defects in cell growth and/or proliferation. During that stage, the mutant larvae develop melanotic masses. Poly is conserved and its homolog, Elp6, is one of the small subunits of the Elongator Complex, a complex involved in many cellular functions including transcription and translation. Drosophila larvae mutated at the Elp3 gene, the gene encoding the catalytic subunit of the Elongator complex, develop melanotic masses, a phenotype very similar to that of poly. The Heck laboratory published that Poly is a positive mediator of the Insulin Receptor/TOR (InR/TOR) pathway, which leads to protein, glycogen and fatty acid synthesis, regulates cell growth and apoptosis. It was shown that Poly interacts with InR, at least in some cases, therefore promoting cell growth and metabolism (Bolukbasi et al., 2012). The Drosophila genome shares 60% similarity to the human, with 77% of the genes attributed to a human disease having a Drosophila counterpart (Chien et al., 2002). In 2011, an intriguing study by Musselman et al. reported that feeding wild type Drosophila larvae with excessive amounts of sucrose led to the development of an insulin resistance phenotype similar to that of Type 2 Diabetes (T2D), thus rendering Drosophila an easily accessible T2D model. The phenotype included impaired metabolism, slower rate of development, and excessive accumulation of triglycerides (TAG) in the larval fat body. In my thesis research, I examined the involvement of Poly in insulin resistance - T2D using Drosophila as a model. The understanding of the connection between the protein and the disease came upon the discovery of a new form of Poly, Poly14. Poly14 is enriched in the Drosophila fat body, the equivalent of the human fat tissue and liver and its protein levels are significantly decreased when larvae are fed a high sucrose diet, compared to other types of diets – potentially linking the protein to the onset of T2D. Poly mRNA levels were also lower. To examine whether the overexpression of poly might be able to rescue the insulin resistance phenotype, two new Drosophila transgenes were generated with the ability to express the gene in a tissue of interest. In these two new transgenes, Poly is tagged with tRFP (Red Fluorescence Protein) at the N’- (UAS_N’RFPpoly) or the C’-terminus (UAS_polyC’RFP). Overexpression of Poly rescued the insulin resistance phenotype, therefore implicating Poly as a possible important regulator in the development of the insulin resistance phenotype. All of the above findings suggest a vital role of Poly in metabolism and the development of the insulin resistance/diabetic phenotype in Drosophila, providing us the opportunity for new tools in this very medically-relevant field of research.

acase@tulane.edu / Study aim: This study aimed to assess the individualized treatment goals (A1C, Blood Pressure, LDL-C) for patients with type 2 diabetes mellitus (T2DM), which lead to optimal health outcomes by different treatment strategies. Background and significance: The evidences in medical guidelines came from clinical trials with highly selected patients, whereas the treatment goals may differ in some subgroups. Additionally, considerable confusions on treatment target has resulted from recent changes in guidelines. So, there is a critical need to examine heterogeneity in optimal goals that lead to the most efficacious treatment options. Methods: A retrospective longitudinal study was conducted for veterans with T2DM by using US Veterans Affairs (VA) Administrative Database (Jan 2005 and Dec 2015). Longitudinal medical records were prepared for each 6-month cycle and multivariate longitudinal regression was used to estimate the risk of microvascular and macrovascular complication events and mortality. Second-degree polynomial and splines were applied in the model to identify the optimal goals in their associations with lowest risk of clinical outcomes by controlling the demographic characteristics, medical history, and medications. Results: 124,651 patients with T2DM were selected, with 62.68 years old (SD=10.96) and 6.72 (SD=6.68) follow-up years at average. In general population, A1C=6.06, LDL-C=106.10 and BP=137.90/98.00 were associated with lowest mortality risk. As of achieving lowest risk of microvascular and macrovascular complication, the optimal goals were A1C=6.81, LDL-C=109.10; and A1C=6.76, LDL-C=111.65, SBP=130.60 respectively. The optimal goals differed between age and racial subgroups. Lower SBP for younger patients and lower LDL-C for blacks were identified with better health outcomes. Conclusions: Individualized treatment goals were identified and multi-faceted treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may improve health outcome in veterans with T2DM. In addition to general ADA recommended goals, health system may examine their own large, more diverse patients with T2DM for better quality of care. / 1 / Qian Shi

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.

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.

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.

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.