published_or_final_version / Community Medicine / Master / Master of Public Health

No description available.

No description available.

二型糖尿病和肥胖症業已成為威脅人類健康的世界性難題。二型糖尿病和肥胖症與心血管疾病的發生發展緊密相關，這是患者致死致殘的最常見原因。因此，揭示糖尿病和肥胖導致心血管疾病的細胞機制，發展更有效而低副作用的治療策略是目前極需研究的課題。本論文主要對以下幾個方面進行了研究探討，第一，在糖尿病和肥胖小鼠中，內質網應激和氧化應激在其內皮功能障礙中的病理學作用；第二，內質網應激能否成為干預靶點；第三，運動鍛鍊改善內皮功能和降低血管炎症，是如何通過限制內質網應激及調節其他糖尿病和肥胖相關的細胞機制來實現的。 / 論文的第一部份揭示了內質網應激及氧化應激在糖尿病內皮功能障礙中所起的關鍵作用。離體組織培養實驗結果顯示，內質網應激誘導劑衣霉素可以顯著地損傷乙酰膽鹼誘導的血管內皮依賴性舒張（EDR），並增加活性氧自由基（ROS）的產量。用內質網應激緩和劑四苯基乙酸（4-PBA）和牛磺酸共軛熊脫氧膽酸（TUDCA）處理血管，可以修復衣霉素和其他風險因子，如高糖，骨形成蛋白4（BMP4）等損傷的血管舒張。類似，ROS清除劑可以減輕衣霉素誘導的EDR損傷。此外，衣霉素可以抑制元代培養的小鼠主動脈內皮細胞的一氧化氮（NO）產量，而這種抑制效果可以被4-PBA和TUDCA逆轉。對db/db糖尿病小鼠用PBA和TUDCA進行慢性口服治療後，內皮功能得到明顯改善，上調的內質網應激得以恢復正常，同時一氧化氮合酶（eNOS）的活性顯著提高，這些結果支持了內質網應激在糖尿病中的病理學作用，提供了內質網應激緩和劑治療糖尿病內皮障礙的的可能性。 / 論文的第二部份研究了過氧化物酶体增殖物活化受體δ(PPARδ) 在抗糖尿病藥物二甲雙胍誘導的腺苷單磷酸活化蛋白激酶（AMPK）激活對血管保護中的作用，及其與內質網應激的聯繫。實驗結果顯示，在食誘導肥胖（DIO）的PPARδ野生型小鼠中，慢性口服二甲雙胍治療可以改善EDR，抑制內質網應激的標誌性蛋白表達和ROS的過高產量，並提高主動脈eNOS的磷酸化水平。這些血管保護效應在PPARδ敲除的DIO小鼠中消失。體內實驗的結果在體外得以證實，二甲雙胍改善EDRs，提高PPARδ的表達和eNOS的磷酸化，抑制小鼠主動脈內質網應激標誌物的表達，並提高了小鼠內皮細胞的NO產量。所有這些效應都可以被PPARδ的抑製劑GSK0660阻斷。這些結果闡明了在AMPK激活劑作用條件下，PPARδ在降低內質網應激，抑制氧化應激和提高NO產量中的顯著作用。 / 生活方式的優化，例如日常的體育鍛鍊，一直以來就被視為改善血管和代謝的重要方式，但這其中的機制並不完全清楚。因此，論文的第三部份主要探索了運動對血管的改善作用。實驗結果顯示，對db/db糖尿病小鼠進行跑步訓練后，導管動脈和阻滯動脈的EDR得到明顯改善，過高內質網應激，炎性反應和氧化應激，以及內皮細胞中被抑制的AMPK和eNOS都會恢復正常。此外，運動對血管功能的保護作用在DIO的PPARδ 野生型小鼠中可以實現。但是，在DIO的PPARδ敲除小鼠中，增加的內質網應激及其氧化應激卻不因運動鍛鍊而降低。這些結果揭示了糖尿病和肥胖中，PPARδ作為保護血管功能的運動誘導信號的關鍵效應器。 / 總而言之，論文的研究提供了一系列新穎的機制和證據，支持了AMPK依賴的PPARδ激活和內質網應激緩解作為潛在的治療策略用於抵抗糖尿病血管病變。這些新發現同樣也為二甲雙胍在臨床上的使用提供了有益的信息，同時為代謝綜合徵病人通過增強運動機能來有效地保護血管功能提供了有效參考。 / Type 2 diabetes mellitus and obesity increasingly represent a global health problem and are associated with the development and progression of cardiovascular disease which is one of leading causes of mortality and disability worldwide. Hence, there is an urgent need to delineate clearer cellular mechanisms of cardiovascular outcomes in diabetes and obesity, and to develop more effective therapeutic strategies with fewer side effects. The present study aimed at examining (1) the pathological role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) over-production in the induction of endothelial dysfunction in diabetic and obese mice, (2) whether ER stress is a therapeutic target, and (3) whether physical exercise improves endothelial function and reduces vascular inflammation through limiting ER stress and other regulatory cellular mechanisms involved in diabetes and obesity. / The first set of experiments show that ER stress and associated oxidative stress serves as a key contributor to endothelial dysfunction in diabetes. The results from ex vivo tissue culture with aortas show that ER stress inducer tunicamycin markedly impairs acetylcholine-induced endothelium-dependent relaxations (EDR) in company with elevated ROS production. Treatment with ER stress alleviators 4-phenyl butyric acid (PBA) and taurine-conjugated ursodeoxycholic acid (TUDCA) restore the impaired relaxations in arteries treated with tunicamycin and other risk factors, high glucose and bone morphogenic protein 4 (BMP4). Likewise, ROS scavengers attenuate tunicamycin-induced impairment of EDR. In addition, tunicamycin reduces nitric oxide (NO) production in primary culture mouse aortic endothelial cells; and its inhibitory effect on NO bioavailability was reversed by co-treatment with PBA and TUDCA. Chronic daily oral administration of PBA and TUDCA rescues endothelial function, normalizes the upregulation of ER stress and oxidative stress, and enhances endothelial NO synthase (eNOS) activity in the aortas from db/db mice, thus supporting a pathological role of ER stress as well as the therapeutic potential of ER stress alleviators in preserving endothelial function with diabetes. / The second series of experiments examined the role of peroxisome proliferator-activated receptor delta (PPARδ) in vascular benefits of activation of AMP-activated protein kinase (AMPK) induced by the anti-diabetic drug metformin in connection with ER stress. Chronic oral metformin treatment improves EDR, inhibits the expression of ER stress markers and ROS over-production, and increases phosphorylation of eNOS in aortas from diet-induced obese (DIO) PPARδ wild-type (WT) mice. These beneficial effects were absent in DIO PPARδ knockout (KO) mice. The benefits of chronic metformin administration are supported by the in vitro data showing that metformin ameliorates EDR, increases PPARδ expression and eNOS phorsphorylation, and suppresses the expression of ER stress markers in mouse aortas; and enhances NO production in mouse endothelial cells. All these effects were blocked by PPARδ antagonist GSK0660. The present results support a significant role of PPARδ in contributing to the reduced ER stress and oxidative stress, and to the increased NO production upon stimulation with AMPK activator. / Lifestyle modification such as regular physical exercise has long been appreciated for its vascular and metabolic benefits though the underlying mechanisms which are not fully understood. The third group of experiments explored the vascular benefits of exercise. Physical running exercise improves EDR in conduit and resistance arteries from db/db mice by normalizing the increased expression or levels of ER stress, inflammation, and oxidative stress, as well as by restoring the diminished activities of AMPK and eNOS in endothelial cells. Vascular benefits were also observed in DIO PPARδ WT mice. However, increased ER stress and associated oxidative stress cannot be reduced by exercise in DIO PPARδ KO mice. These results elucidate that PPARδ serves as a key mediator of exercise-induced signaling that mediate the vasoprotective effect of exercise in diabetes and obesity. / To summarize, the present investigation has provided several lines of novel mechanistic evidence in support for the positive role of AMPK-dependent PPARδ activation and ER stress alleviation as potentially therapeutic target to combat against diabetic vasculopathy. The new findings of the present study also provide useful information in support of the clinical utilization of metformin and recommendation of increased physical activity as another effective measure to preserve vascular function in patients with metabolic syndrome. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Cheang, Wai San. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 131-152). / Abstracts also in Chinese.

The isolated perfused working heart was used to study hypertensive- diabetes induced alterations in cardiac function at 6 and 12 weeks after the induction of diabetes. There was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats at 6 weeks after diabetes induction. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-week study. Successful induction of diabetes was confirmed by the presence of hyperglycemia, hypoinsulinemia, glycosuria and increased haemoglobin glycosylation in all three diabetic groups. However, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups, associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats and could explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than is seen with either disease alone and is associated with a significant mortality. The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). When hydralazine was administered for a 6-week period to the diabetic rats, their blood lipids were not significantly different from that of non-diabetic rats despite a low serum insulin. In contrast, blood lipids were elevated in the diabetic rats that were not treated with hydralazine; these animals also had low insulin levels. Cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement which could be partly explained by their normal thyroid status in contrast to the untreated diabetic animals which were slightly hypothyroid. Blood pressure was elevated only in the untreated diabetic animals. Thus hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats. To examine the influence of sex differences in the STZ model of diabetes, we studied left ventricular function in hearts from 6 week male and female rats. Significantly lower values for +dP/dt occurred in male diabetic rats compared with their own controls or female diabetics at most left atrial filling pressures. Decreases in this value for female diabetic rats compared to their own controls occurred only at high left atrial pressures. It appears that diabetes mellitus produces greater myocardial dysfunction in male diabetic rats. / Pharmaceutical Sciences, Faculty of / Graduate

Thesis (M Med (Family Medicine) -- University of Limpopo, 2011. / Introduction The burden of type 2 diabetes mellitus continues to rise and constitutes a real threat especially in the developing world. As for most non-communicable diseases, change of behavior and adoption of healthy lifestyle habits help to prevent and slow down the increase of type 2 diabetes mellitus. Aim of the Study To establish the knowledge, attitudes and practices regarding lifestyle modifications among type 2 diabetic patients attending the diabetic clinic at Mamelodi hospital. Methods: This cross sectional study describes the knowledge, attitudes and practices regarding lifestyle modifications (KAP) among 217 type 2 diabetes mellitus patients attending Mamelodi Hospital, Pretoria, Republic of South Africa. A face-to-face interview using a structured questionnaire was carried out for data collection. Socio-demographic characteristics of the participants and anthropometric measurements were obtained and the body mass index (8MI) of participants were determined. The Knowledge, attitude and practice of participants were assessed. 2 Results: Majority of participants were female 176(81.1 %), while male were 41 (18.9%). This amounted to a female to male ratio of 4:1. Most participants were in the age group 51-60 years 93(42.9%). Majority of them had low level of education 108(49.5%) and low income 206(94.9%). Majority of participants were obese 153(71 %) with more female diabetic patients being obese 120 (78.4%) than male 33 (21.6%). 15 participants (14 females and 1 male) were morbidly obese (BMI~40kg/m2). 108 participants (49.5%) did not have a formal education. No respondent had good knowledge and 92.6% of respondents had poor knowledge of the benefits of exercise, weight loss and healthy diet. Majority of respondents (97.7%) had bad practices in relation to lifestyle modifications. Nevertheless, majority of them (84.3%) had positive attitudes toward lifestyle modifications. Significant positive correlation (r= 0.170, p=0.012) was found between the global knowledge level and attitude level alone, whereas there was no significant correlation found between the global knowledge level and practice level as well as the attitude level and practice level. Conclusion: In conclusion, despite positive attitudes of participants toward healthy lifestyle habits, the knowledge and practices regarding lifestyle modifications among type 2 diabetes mellitus patients attending Mamelodi Hospital were generally low. Nevertheless the positive attitudes of participants should be encouraged and the implementation of a lifestyle intervention program will help improve the knowledge and practices of type 2 diabetes mellitus patients attending Mamelodi Hospital for the better management and control of this current pandemic of type 2 diabetes mellitus.

Thesis (MFamMed)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Introduction: Diabetes is the most prevalent endocrinology problem encountered in primary care practice. If recent trends showing a dramatic increase in prevalence (believed to be a consequence of a decline in physical activity and excessive caloric intake) continue, then the condition will soon affect nearly 20 million people in the U.S a reflection of the global trend. Effective management requires care that is thoughtful and meticulous, incorporating intensive patient education. Euglycemic control, with the level of glycosylated haemoglobin (HbA1c) kept below 7.0mmol/L, has emerged as a major treatment objective because of its association with a marked reduction in the risk for micro vascular complications. The primary physician is in the unique position to provide comprehensive care to the diabetic patient. Setting: The aim of this study is to evaluate the profile of complications arising due to diabetes mellitus among adult diabetics attending internal medicine outpatient department and family medicine/primary care outpatient department in the Dora Nginza hospital, PE hospital complex. Method: The study is a descriptive retrospective study in which names of patients were collated from clinic records of both clinics, files sought at the records department covering the period between Jan 2007 and Jan 2008 inclusive. Prevalence of statistical variables was generated using frequency tables, bar graphs, cross tabulations and chi square test. Results: Hyperglycemia was the major complication which predominantly was associated with high haemoglobin A1c (HbA1c) levels. However, some hyperglycaemic cases were also found to be associated with normal HbA1c. Complications were found to be more in type 2 diabetics. Patients with hypertension, obesity, smoking and alcohol use were observed to have a higher risk of developing diabetic complications. The findings on retinopathy in this study was inconclusive in view of the fact that patients sent for fundoscopy did not return with documented results from the sister hospital PE provincial hospital. Family Medicine outpatient department overall did better in patient care compared to the Internal Medicine outpatient department. Conclusion: The challenge for the primary care physician is to design a therapeutic program that is safe practical and acceptable to the patient. The ultimate goal of therapy is the prevention of micro vascular and macro vascular complications, consequence of diabetes that makes the condition a major risk factor for cardiovascular disease, stroke, visual impairment, renal failure, impotence, peripheral neuropathy, limb loss and ultimately death. These can be averted through appropriate education of both hospital staff, patients and their care givers. The recommendations made are based on the findings of the study. / AFRIKAANSE OPSOMMING: Nie beskikbaar.

published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Thesis (M Med (Family Medicine))--University of Limpopo, 2010. / The number of diabetic patients will continue to rise even in rural settings and the burden of this disease will continue to take its effect on the limited resources of these communities. The effect of such burden will be more pronounced if we are to add the various complications associated with substandard management of diabetes mellitus. The first step in assessing the level of care we give to this category of patients is to measure their level of adherence, in an effort to expose the pitfalls on both the side of the patients and on the side of the health care provider. The aim of the study is to assess the level of adherence to treatment among type2 diabetic patients in Matlala district hospital; Limpopo Province. This cross-sectional study used the convenience method of sampling with the aid of a tested, structured questionnaire, to obtain data from respondents between December 2009 and March 2010, a period of 4 months. The excel computer program was used for data capturing. Percentages and numbers were used for interpretation and cross tabulation was used to determine association. The result of the study indicated that 137 {70%} of the respondents adhere to diabetes treatment. There were two demographical characteristics that are significantly associated with non adherence: age {p=0.028} and employment status {p=0.018}. Of those respondents that keep their appointments, 98% are adherent to treatment. When considering reasons for poor adherence; 29% of respondents stated that the clinic did not have their pills, 16% stated that they forgot to take their medication and 14% stated that they travelled to visit ix and did not take enough pills with them. On the reasons for poor adherence to lifestyle: 29% of the respondents said that they were too old, 22% stated no specific reason, 13% struggled to motivate themselves and 10% simply forgot what to do. Most, 68%, of the respondents that adhere to the recommended use of medication agreed that they take it at meal time, 14% set a reminder, 8% employed the assistance of a treatment supporter and other respondents used other means to remember. The study revealed an above average level of adherence in my setting and it will be logical to assess whether this corresponds to the metabolic control expected of good adherence. More is needed to be done on the reasons why our patients do not adhere to both medication and lifestyle changes and each stake holder needs to address their short comings.