BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) has been identified as a potential risk factor for developing type 2 diabetes mellitus (T2DM). Given the rising prevalence of T2DM and unhealthy concentrations of PM2.5 in China, our attention is brought to examining the association in this region of the world. Furthermore, rural China, although largely ignored, also finds itself suffering from increased risks of T2DM and high levels of PM2.5. OBJECTIVE: The goal of this study is to characterize the relationship between long-term exposure to PM2.5 and the risk of T2DM in rural China. We do so by confirming that greater long-term exposure to PM2.5 is associated with a higher risk of T2DM incidence, assessing the potential multiplicative and additive interactions with important covariates, and identifying constituents of PM2.5 that may be responsible for the effect PM2.5 on the increased incidence of T2DM. CONCLUSIONS: Greater long-term exposure to PM2.5 is associated with increased risk of developing T2DM in rural Deqing County, Zhejiang, China. Smoking status modifies the relationship between PM2.5 and T2DM incidence on a multiplicative scale. There is no synergism between smoking and PM2.5 in association with T2DM incidence. There is no conclusive evidence on which constituents of PM2.5 play greater roles in the adverse effects of PM2.5 on T2DM incidence.

Type 2 Diabetes Mellitus (T2DM), a metabolic disorder denoted by elevated blood glucose levels and insufficient insulin action, is growing in prevalence worldwide . Barriers to improving disease outcome resolve primarily around identifying and intervening during the preliminary stages of insulin resistance, a state clinically referred to as pre-diabetes. Emerging evidence suggests that mitochondrial dysfunction may underlie , and potentially precede, progressive insulin resistance, suggesting that biomarkers indicative of mitochondrial dysfunction could predict disease risk and status. In this study, we examined epigenetic modifications, in the form of DNA methylation, in the promoter region of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), a known regulator of mitochondrial biogenesis. Following the initiation of a high fat diet, we observed significant genotypic (DNA methylation) and phenotypic (mitochondrial copy number) alterations in C57/BL6 rodent models. These changes preceded overt disease onset, as classified by clinically utilized indices, which included the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as an effective clinical parameter to use in conjunction with physiological criterion for the diagnosis of pre-diabetes and the assessment of T2DM disease risk, and adds to the growing body of work seeking to elucidate the role. / Doctor of Philosophy / High blood glucose, referred to as type 2 diabetes (T2DM), increases the risk for heart and kidney disease, blindness, stroke, and death. Efforts to prevent T2DM have centered primarily around behavioral interventions, which include increased physical activity and decreased caloric intake. Importantly, the interventions are most effective when implemented early on in disease progression. In this study, we sought to examine the effects of a high fat diet on the epigenetic profile of PGC-1α, a gene responsible for maintaining mitochondrial biogenesis. The mitochondria, the powerhouse of the cell, is responsible for maintaining the energy systems in the body. Therefore, we examined how increasing in caloric intake resulted in changes in the epigenetic profile of the PGC-1α promoter, and how these changes impacted mitochondrial number. Further, we sought to examine how hypermethylation of PGC-1α led to changes in gene and protein expression in the mitochondria. Results from our study indicate that DNA methylation changes preceded disease onset, as characterized by the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as diagnostic and risk assessment tool for pre-diabetes and T2DM in conjunction with physiological measures.

Published research on diabetes in Ghana is quite limited and relates mainly to incidence and prevalence of the disease with little research on the patients experiences of coping with the diabetes. It is estimated that diabetes affects 6.3% of the Ghanaian population with type 2 diabetes accounting for 90-95% of all cases of diabetes. In Ghana, individuals diagnosed with type 2 diabetes mellitus are confronted with difficulties including the high cost of treatment of the condition, stigmatization, and interruptions to normal physiological processes. In addition, the patients experience, limited clinic accessibility, inadequate drug availability, inadequate numbers of trained staff, as well as limited availability of equipment needed for adequate care of the condition. The review of literature for this current thesis also showed that none of the studies on coping were undertaken in Ghana, but were conducted in the western world where socio-cultural factors are quite diverse from the Ghanaian situation. In the light of the challenges facing diabetic patients as well as the gap observed in literature, the study set out to explore the coping strategies of patients with type 2 diabetes mellitus at a hospital in Ghana. A hermeneutic phenomenological approach to qualitative research was utilized. Twenty seven (27) in-depth interviews carried out with newly diagnosed patients with type 2 diabetes, between August and October 2009 at a hospital in Ghana. Interviews were conducted in the local Ghanaian Twi language and English. Participants who could not speak English were interviewed in Twi language and later translated into English by the researcher. Data analysis used Creswell (1998) approach to qualitative data analysis, which provided a rich description of the essential structures of the phenomenon under study. The study identified patients’ perceptions as to the causes of diabetes mellitus, the social meanings attributed to diabetes (with particular attention paid to the language by Ghanaian people to describe disease condition), and subsequently reactions and resolutions to diagnosis. Patients discussed treatment options, while at the same time remaining hopeful of finding a cure. All patients had a firm spiritual belief system that underpinned their understanding of the causation and treatment of their illness. This combined with various degrees of understanding and acceptance of western explanations of illness influenced the coping strategies employed by patients, which variously reported as positive, negative, and alternative strategies. The study establishes a platform upon which health providers can develop educational programmes for diabetic patients in Ghana, which will address misconceptions about diabetes mellitus in Ghana and the importance of programmes of care, which take account of and build upon the cultural context of ‘being Ghanaian’. Diabetes, at least for Ghanaian patients is more than a biomedical disease. In this sense a biomedical framework in and of itself will not enable healthcare providers to effectively manage this chronic disease in the Ghanaian population, but through the inclusion of an understanding of their spiritual beliefs, healthcare providers can understand the realities of what it is like for Ghanaian diabetes patients to live with diabetes. It is argued that a stronger collaboration and integration between traditional healthcare systems and orthodox healthcare systems will provide the optimum opportunity to maximize patient care in Ghana. Future research should concentrate on better understanding how lay knowledge and health related attitudes, beliefs and behaviours are associated with diabetes in Ghana.

Magister Public Health - MPH / Introduction: The control of type 2 diabetes mellitus (T2DM) is pivoted on adherence to a healthy lifestyle (healthy diet, physical activity and non-smoking). Zimbabwe reports a high burden of T2DM related complications suggesting an increased inability by patients to control their blood glucose levels. This study, therefore, sought to describe the healthy lifestyle practices of T2DM patients in Harare, Zimbabwe and associate these practices with their glycated haemoglobin (HBA1C) levels, a marker for the control of diabetes. Methodology: A descriptive cross-sectional study was done. Participants were T2DM patients who were 18 years and older from two tertiary hospital diabetes clinics in Harare. Data collection was done using a structured questionnaire which was interviewer-administered along with height, weight and HBA1C measurements. Descriptive statistics were used to describe the study populations. Chi square test was used to calculate statistically significant associations between healthy lifestyle behaviours and demographics or HBA1C levels at the significant level of 0.05%.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Background Obesity, insulin resistance and type 2 diabetes mellitus (T2DM) have been associated with endometrial cancer (EC). In this systematic review and meta-analysis we evaluated the effect of metformin on clinical outcomes in patients with EC and insulin resistance or T2DM. Methods Four research databases were searched for original articles published in all languages up to 30 October 2016. Outcomes of interest were overall mortality (OM), cancer-specific mortality, disease progression, and metastases. We performed a random effect meta-analysis of adjusted effects expressed as hazard ratios (HR); heterogeneity among studies was described with the I2 statistic. Results Of the 290 retrieved citations, 6 retrospective cohort studies in women with EC (n = 4723) met the inclusion criteria, and 8.9% to 23.8% were treated with metformin; OM data was available from 5 studies. In 4 studies of EC patients (n = 4132), metformin use was associated with a significant reduction in OM in comparison with not using metformin (adjusted HR [aHR] 0.64, 95% CI 0.45–0.89, p = 0.009). In three studies evaluating patients with EC and T2DM (n = 2637), metformin use was associated with a significant reduction in OM (aHR 0.50, 95%CI 0.34–0.74, p = 0.0006). There was low to moderate heterogeneity of adjusted effects across studies. There was no information about the effect of metformin on cancer-specific mortality, disease progression, or metastases. Conclusions Metformin treatment is associated with a significant reduction in OM irrespective of diabetes status in patients with EC. The survival benefit suggests that diabetes screening and maintenance of good glycemic control may improve outcomes in EC. / Revisión por pares

A research report from the Centers for Disease Control and Prevention (CDC) indicated that more than 50% of people with diabetes mellitus (DM) in the United States (U.S.) also have arthritis. The diabetes population is disproportionately affected by arthritis, but there has been limited and inconsistent research to confirm the association between type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA). The current study aimed to identify an association between T2DM and RA for noninstitutionalized U.S. adults between 1999 and 2012 using a nationally representative sample from the National Health and Nutrition Examination Survey (NHANES) database (n =31,488 ). A quantitative, cross-sectional investigation was conducted to determine if patients with T2DM had an increased prevalence of RA. The current study also sought to identify characteristics that could affect the association between both groups and the prevalence of cardiovascular disease (CVD) in this population. Prevalence and adjusted odds ratios (OR) using logistic regression were calculated. The results show evidence of a strong association between T2DM and concomitant RA. Prevalence of RA was significantly higher in participants with T2DM compare to those without T2DM. Important factors in this association were gender, ethnicity, education, disability, and work functioning. The prevalence of CVD and adjusted OR of association were doubled in participants with T2DM and RA when compared to participants who had just one of the conditions; the OR of association was quadrupled when compared to those without this comorbidity. This study may provide patients and health care providers with a better understanding of the need for management of both conditions in a interdisciplinary manner

Glucose transporter GLUT4 allows glucose uptake into muscle and adipose cells. Insulin promotes recruitment and plasma membrane insertion of GLUT4 vesicles that can recycle constitutively. Obesity and type 2 diabetes mellitus are associated with defects in insulin-induced GLUT4 recruitment. Knowledge of alternative modes and steps of GLUT4 traffic in L6-GLUT4myc muscle cells may reveal possible targets for therapeutic intervention in insulin-resistant patients. Hypertonicity and Platelet Derived Growth Factor also increase surface GLUT4 levels but it was unknown if they tap on the same intracellular GLUT4 depots as insulin. We explored whether GLUT4 vesicles recycle using different compartments and mechanisms for the surface gain elicited by each stimulus. We hypothesized that all vesicle fusion steps require NSF but depend on individual v-SNAREs. Specifically, we tested effects of ATPase-deficient NSF or VAMP7 siRNA transfections, and endosomal ablation on GLUT4 traffic. We show that VAMP7 was required for basal and hypertonic recycling, while VAMP2 is exclusively used in response to insulin. As insulin action bifurcates downstream of phosphatidylinositol 3-kinase, we also hypothesized that the Rac-to-actin and Akt-to-AS160 branches regulate distinct GLUT4 traffic steps. For this we determined GLUT4myc localization in rounded myoblasts relative to a surface marker. Interfering with Rac, actin dynamics or actin-binding α-actinin4 maintained GLUT4 in a perinuclear region even under insulin-stimulation. Interfering with AS160 allowed significant GLUT4 accumulation beneath the membrane, but not fusion. We propose that actin dynamics and α-actinin4 are required for cortical GLUT4 tethering mechanisms, and AS160 contributes to GLUT4 docking/fusion. We confirmed that VAMP2 facilitates GLUT4 fusion, as tetanus toxin-based cleavage did not inhibit peripheral GLUT4 recruitment. Finally, AS160 targets Rab8A and Rab14 in muscle respectively affected GLUT4 availability for membrane fusion, and basal GLUT4 retention. This work will lead to future testing of strategies to selectively enhance vesicle availability, tethering, or surface fusion, for bypassing insulin resistance.

Canadian statistics indicate that the incidence of obesity is rising, and that the prevalence of type 2 diabetes mellitus (T2DM) within this group is significantly higher than those of a healthy weight. Preliminary evidence has shown that the oil-rich grain, Salvia hispanica L. (Salba), improves glycemic control, suppresses appetite, and affects additional cardiovascular disease (CVD) risk factors. This study followed a randomized, double-blind, placebo-controlled, parallel design in a sub-set population of twenty individuals who were overweight or obese and had T2DM. Participants received supplements of Salba, or an energy- and fibre-matched control, and followed a hypocaloric diet for 24 weeks. Findings of this study reveal that Salba does not significantly affect weight loss, glycemic control or other CVD risk factors. These findings are preliminary and highlight the complexities of weight loss research. Further investigation into the potential health benefits of Salba is currently being carried out.

Canadian statistics indicate that the incidence of obesity is rising, and that the prevalence of type 2 diabetes mellitus (T2DM) within this group is significantly higher than those of a healthy weight. Preliminary evidence has shown that the oil-rich grain, Salvia hispanica L. (Salba), improves glycemic control, suppresses appetite, and affects additional cardiovascular disease (CVD) risk factors. This study followed a randomized, double-blind, placebo-controlled, parallel design in a sub-set population of twenty individuals who were overweight or obese and had T2DM. Participants received supplements of Salba, or an energy- and fibre-matched control, and followed a hypocaloric diet for 24 weeks. Findings of this study reveal that Salba does not significantly affect weight loss, glycemic control or other CVD risk factors. These findings are preliminary and highlight the complexities of weight loss research. Further investigation into the potential health benefits of Salba is currently being carried out.

Glucose transporter GLUT4 allows glucose uptake into muscle and adipose cells. Insulin promotes recruitment and plasma membrane insertion of GLUT4 vesicles that can recycle constitutively. Obesity and type 2 diabetes mellitus are associated with defects in insulin-induced GLUT4 recruitment. Knowledge of alternative modes and steps of GLUT4 traffic in L6-GLUT4myc muscle cells may reveal possible targets for therapeutic intervention in insulin-resistant patients. Hypertonicity and Platelet Derived Growth Factor also increase surface GLUT4 levels but it was unknown if they tap on the same intracellular GLUT4 depots as insulin. We explored whether GLUT4 vesicles recycle using different compartments and mechanisms for the surface gain elicited by each stimulus. We hypothesized that all vesicle fusion steps require NSF but depend on individual v-SNAREs. Specifically, we tested effects of ATPase-deficient NSF or VAMP7 siRNA transfections, and endosomal ablation on GLUT4 traffic. We show that VAMP7 was required for basal and hypertonic recycling, while VAMP2 is exclusively used in response to insulin. As insulin action bifurcates downstream of phosphatidylinositol 3-kinase, we also hypothesized that the Rac-to-actin and Akt-to-AS160 branches regulate distinct GLUT4 traffic steps. For this we determined GLUT4myc localization in rounded myoblasts relative to a surface marker. Interfering with Rac, actin dynamics or actin-binding α-actinin4 maintained GLUT4 in a perinuclear region even under insulin-stimulation. Interfering with AS160 allowed significant GLUT4 accumulation beneath the membrane, but not fusion. We propose that actin dynamics and α-actinin4 are required for cortical GLUT4 tethering mechanisms, and AS160 contributes to GLUT4 docking/fusion. We confirmed that VAMP2 facilitates GLUT4 fusion, as tetanus toxin-based cleavage did not inhibit peripheral GLUT4 recruitment. Finally, AS160 targets Rab8A and Rab14 in muscle respectively affected GLUT4 availability for membrane fusion, and basal GLUT4 retention. This work will lead to future testing of strategies to selectively enhance vesicle availability, tethering, or surface fusion, for bypassing insulin resistance.