Diabetic pregnancy is associated with increased risk of congenital malformations. Previous studies have shown that maternal diabetes can interact with the vitamin A metabolite, all-trans retinoic acid (RA), in increasing embryonic susceptibility to caudal regression and neural tube defects. The aim of this thesis is to investigate the cellular and molecular mechanisms that underlie this interaction. / First hypothesis. RA concentration in the embryo is tightly regulated by the synthesizing enzyme retinaldehyde dehydrogenase type II (RALDH2), and the degrading enzyme CYP26. Alteration in expression levels of these enzymes under maternal diabetes may affect the availability of RA and thus its teratogenicity. / In conclusion, results of this thesis provide insight into the mechanism of how maternal diabetes interacts with RA in enhancing embryonic susceptibility to congenital malformations. This is also the first report to show that maternal diabetes alters RA homeostasis. (Abstract shortened by UMI.) / Second hypothesis. The transfer of RA to the nucleus for molecular action is regulated by cytoplasmic cellular retinoic acid binding proteins CRABP-I and CRABP-II. Alteration in expression levels of these binding proteins under maternal diabetes may affect the amount of RA reaching the nucleus and thus its teratogenicity. / Third hypothesis. The action of RA is mediated via different nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Alteration in expression levels of these receptors under maternal diabetes may affect the efficacy of RA signal transduction and thus its teratogenicity. / Three hypotheses are proposed to explain the underlying mechanism of increased embryonic susceptibility to RA teratogenicity under maternal diabetes: / To investigate these hypotheses, expression levels of various genes in different groups were compared. Result show that there are no significant differences in mRNA expression levels of CRABP-I, CRABP-II, RARgamma, RARgamma and RXRalpha between embryos of diabetic and non-diabetic mice with or without RA treatment. In contrast, expression levels of Raldh2 and CYP26 are significantly reduced in embryos of diabetic mothers, and in embryos of non-diabetic mice cultured in vitro in hyperglycemic conditions. Moreover, embryos of diabetic mice show significantly reduced response to RA-induced up-regulation of CYP26. These findings suggest that the rate of degradation of RA is slower in embryos of diabetic mice and thus the teratogenic effect of RA is enhanced. / Leung Bo Wah. / "July 2005." / Adviser: Alisa S. W. Shum. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3779. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 158-198). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (M. A. (Nursing Science)) -- University of Limpopo, 2019 / Background: Non-attendance of diabetic patients at primary health care facilities for scheduled appointments has been identified as one of the most pressing issues in chronic illness, including diabetes mellitus, management and results into uncontrolled illnesses. Diabetes mellitus has an increased mortality and morbidity rate, thus has been identified as the second most frequent killer disease in South Africa. Aim of the study: The purpose of the study is to determine self-management strategies to maintain a healthy life for diabetic patients under treatment in primary health care facilities in the Sekhukhune District. Methods: A qualitative, phenomenological, explorative and descriptive study design was conducted in 5 clinics of the Sekhukhune District in the Elias Motswaledi Municipality in Limpopo Province. Data were collected through one-to-one interviews using semi-structured guide. An non-probability purposive sampling method was used to select participants until data saturation was reached. Data were analysed using Tech’s coding qualitative data analysis approach. Results: The findings of this research reveal that diabetic patients know the importance of adherence to diet. However, they also elaborated on the challenges they face, like inability to afford proper diet and their stress levels. They are aware of predisposing factors and recommend support structures like food parcels as well as adhering to the prescribed treatment. Conclusion and recommendations: Diabetic patients lack self-management strategies to maintain their quality of life when diagnosed with diabetes. Furthermore, the study concludes that diabetics lack encouragement and empowerment from health care workers and their families. The study recommends that diabetic patients adhere to a prescribed diet and treatment and that they could be offered food parcels and taught how to avoid factors that could trigger stress. Additionally, it is recommended that support structures be developed to assist diabetic patients about self-management strategies that they could use in order to maintain a good quality of v life. It is also recommended that the Department of Health employ Home-Based Carers in the facilities to assist diabetic patients with their day-to-day care.

Mini-dissertation was submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2012. / It was reported by the International Diabetes Federation (IDF) Diabetes Atlas, in 2003, that a prevalence figure of 3.4% exists for the 24 million South Africans between the ages of 20 and 79, with an expected increase to 3.9% by 2025. Considering that patients with diabetes are at increased risk of cardiovascular disease, blindness, amputation and renal failure it is therefore not surprising that the costs associated with diabetes are estimated to increase worldwide. It is clear that according to the current trends in dietary and exercise practices, South Africa will be affected by the rise in obesity and subsequent diabetes mellitus. It is critical that a concerted effort involving all parties concerned be made to combat this rapidly increasing problem (Rheeder, 2006:20). AIM The purpose of this double-blind, randomized clinical trial was to compare the effectiveness of Momordica charantia homoeopathic mother tincture as compared to Momordica charantia 6CH, in the treatment of type 2 diabetes mellitus in patients on Metformin. METHODOLOGY Thirty patients were recruited and were selected for the study on the basis of inclusion and exclusion criteria. These participants were then randomly and equally divided into two groups. Each participant attended a total of four consultations with the researcher, over a two month period, at the Durban University of Technology (DUT) Homoeopathic Day Clinic. At the commencement of the first consultation, each participant received the subject information letter (Appendix A) for perusal and the informed consent form (Appendix B) to sign. Following this, the researcher took a full, detailed iv case history (Appendix F) and performed a physical examination (Appendix G) of each patient. Participants were required to have a Glycosylated haemoglobin (HbA1C) test performed following the first and fourth consultations. Participants were also required to complete daily Log Sheets (comprising self administered fasting blood glucose readings using issued Bayer Ascensia Elite Glucometers) for the entire duration of the study (8 weeks). SPSS version 18 was used to analyse the data. A p value < 0.05 was considered as statistically significant. The time effect was assessed for intra-group comparison whereas the time x group treatment effect was assessed for inter-group comparison. Means were calculated for both fasting blood glucose and glycosylated haemoglobin for the two respective groups and tabulated in order to describe the data obtained (Descriptive statistics). RESULTS Both groups reflected a statistically non significant decrease in fasting blood glucose levels with no significant differences between the two groups when comparing reduction in fasting blood glucose levels. Group 1 (Momordica charantia homoeopathic mother tincture) reflected a non significant increase in glycosylated haemoglobin (HbA1C) levels while Group 2 (Momordica charantia 6CH) reflected a statistically significant increase over time in HbA1C levels. There were no significant differences between the two groups when comparing reduction in HbA1C levels. / M

Thesis (MCur)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Complications of chronic conditions pose serious consequenses for the patient and financial implications for the health authorities, in the form of serious procedures, adaptions of medication, hospitalisation or rehabilitation. The goal of the study was to investigate the management of patients with diabetes mellitus type 2 on primary health care level. The objective of the study: • a retrospective investigation into the holistic management of patients with diabetes mellitus type 2 by CNPs. The research design was descriptive, non-experimental with a quantitative approach. The population included 896 files of patients diagnosed with diabetes mellitus type 2 over a period of 6 months at 4 clinics in the George Subdistrict. The sample consisted of 180 files, namely 20% of the population. The researcher gathered the data personally by means of a structured check list. Ethical approval was obtained by Stellenbosch University and above mentioned health authorities. Reliability and validity was ensured by means of a pilot study, as well as inputs from a statistician, experts in the fields of primary health care and a research panel. Descriptive statistics were used for data-analysis. Variables were presented in the form of tables, graphs and frequencies. Statistica Version 9 software were used and relations between the various variables were analysed by means of ANOVA (“Analysis of Variance”). By means of systematic probability sampling every second file that adhered to the inclusion criteria was drawn, until 20% saturation was reached at each clinic. Thereafter every second file was drawn from the rest of the appropriate files, until the sample was sufficient or until there were no more suitable files left over. The results of this study provide evidence that the holistic approach was not constantly applied by CNPs in patients with diabetes mellitus type 2. Drug treatment was renewed by a doctor every six months, but no attention was given to the diabetes mellitus in between the doctor's visits. Health information was given. It varied between 100% to 81%. Complications were not addressed appropriately though. In clinic A for example 6% (n=5) recorded on the condition of the patients' feet, while in clinic B 4% (n=2) addressed this issue. At clinic C nothing was recorded on this aspect, while at clinic D 13% (n=2) recorded on this. Respiratory and cardio-vascular systems often fail in patients with diabetes mellitus type 2. At clinic A CNPs enquired only in 18% (n=16) of cases about these systems, at clinic B 22% (n=11), at clinic C 27% (n=7) and at clinic D 6% (n=1). This study has the potential to stimulate further research, especially regarding the reasons why CNPs do not manage chronic patients holistically. / AFRIKAANSE OPSOMMING: Komplikasies van kroniese toestande het gevolge vir die pasiënt en koste-implikasies vir die gesondheidsdienste, byvoorbeeld ernstige ingrepe, medikasieaanpassings, hospitalisasie of rehabilitasie. Die doel van die studie was om te bepaal hoe KVPs pasiënte met diabetes mellitus tipe 2 op primêre gesondheidsorgvlak hanteer. Die doelwit van die studie: • retrospektiewe waarneming na die holistiese hantering van pasiënte met diabetes mellitus tipe 2 deur KVPs. Die navorsingsontwerp was beskrywend, nie-eksperimenteel, met ‘n kwantitatiewe benadering. Die populasie was 896 lêers van pasiënte wat oor ses maande met diabetes mellitus tipe 2 gediagnoseer was by vier klinieke in die George Subdistrik. Die steekproef was 180 lêers, naamlik 20% van die populasie. Die navorser het persoonlik data ingesamel met ‘n gestruktureerde kontrolelys. Etiese goedkeuring is verleen deur die Universiteit van Stellenbosch en bogenoemde gesondheidsowerhede. Betroubaarheid en geldigheid is verkry deur ‘n loodstudie en deur insette van 'n statistikus, primêre gesondheidsorg eksperts, asook 'n navorserspaneel. Beskrywende statistieke is aangewend vir data-analise. Veranderlikes is voorgestel in die vorm van tabelle, grafieke en frekwensies. Statistica Version 9 sagteware is gebruik en verhoudings tussen veranderlikes is geanaliseer deur van ANOVA (“analysis of variance”). Deur middel van sistematiese waarskynlikheidsteekproefbepaling is elke 2de lêer wat aan die insluitingskriteria voldoen het getrek, tot 20% saturasie by elke kliniek bereik is. Verder is elke 2de lêer uit die oorblywende lêers getrek, totdat die hoeveelheid genoeg was, of totdat daar nie meer geskikte lêers was nie. Resultate van hierdie studie bewys dat pasiënte met diabetes mellitus tipe 2, nie holisties hanteer was deur KVPs nie. Medikasie was meestal elke 6 maande deur 'n dokter hernu, sonder enige aandag aan die diabetes mellitus tipe 2 gedurende die tussen-in periodes. Gesondheidsvoorligting was goed. Dit het gewissel van 100% tot 81%. Komplikasies was egter onvoldoende aangespreek. In kliniek A het byvoorbeeld 6% (n=5) oor die toestand van die pasiënte se voete gerekordeer, terwyl in kliniek B 4% (n=2) hiervan melding gemaak het. By kliniek C was daar niks hieroor aangeteken nie, terwyl by kliniek D 13% (n=2) hieroor gerekordeer het. Respiratoriese en kardiovaskulêre sisteme versaak dikwels by pasiënte met diabetes mellitus tipe 2. By kliniek A het KVPs slegs by 18% (n=16) navraag gedoen oor hierdie sisteme, by kliniek B 22% (n=11), by kliniek C 27% (n=7) en by kliniek D 6% (n=1). Hierdie studie behoort verdere navorsing te stimuleer, veral oor die redes hoekom die KVPs nie kroniese pasiënte holisties hanteer nie.

Thesis (MA)--University of Stellenbosch, 2003. / ENGLISH ABSTRACT: Individuals diagnosed with diabetes mellitus are at an increased risk for developing depression. According to the literature, depression in diabetes mellitus has been associated with a poorer quality of life, poorer regimen adherence, poorer adjustment to diabetes, poorer glycaemic control, and an increased risk of developing diabetes related complications. While the role of certain psychosocial determinants in the onset and maintenance of depression has been investigated, mental health professionals and researchers have neglected the task of conceptualizing the relationship between depression and diabetes from a psychological perspective. This assignment presents a psychological conceptualization of the relationship between diabetes and depression, using Beck's (1967, 1979) cognitive model of depression as a framework. This conceptualization may serve as a means of theoretically understanding the relationship between these two conditions and as a framework in directing future research on this relationship. / AFRIKAANSE OPSOMMING: Individue wat met diabetes mellitus gediagnoseer word, toon 'n verhoogde risiko om depressie te ontwikkel. Volgens die literatuur word depressie in diabetes mellitus geassosieer met 'n swakker lewensgehelte, swakker nakoming van behandeling, swakker aanpassing by diabetes, swakker glisemie-kontrole, en 'n verhoogde risiko om diabetes verwante komplikasies te ontwikkel. Hoewel die rol van bepaalde psigososiale verandelikes in die ontstaan en instandhouding van depressie reeds ondersoek is, is min nog gedoen oor 'n konseptualisering van die assosiasie tussen diabetes en depressie. Hierdie werkstuk handeloor 'n konseptualisering van die verband tussen diabetes en depressie, gebaseer op Beck (1967, 1979) se kognitiewe model van depressie. Die konseptualisering dien as 'n naamwerk om hierdie verband te verstaan en toekomstige narvorsing hieroor te rig.

published_or_final_version / Social Work / Master / Master of Social Work

Leung, Siu Lun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 153-190). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Chan Wai-Hon. / "September 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 137-156). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

In this 15 year follow up study in a Chinese population, we confirmed that maternal gestational diabetic status significantly increased women’s future cardiometabolic risk. Glycaemic levels below the current criteria for a positive screening test for gestational diabetes and for the diagnosis of gestational diabetes still significantly predict women’s future risk. In utero hyperinsulinaemia, which caused by an intrauterine hyperglycaemic environment, was found to predict children’s AGT and adolescents’ overweight and MetS. The results had important implication that the current diagnostic criteria for gestational diabetes may not be discriminative in predicting both the mothers and their children’s future cardiometabolic risk. Although recent research has re-visited and emphasised on the diagnostic criteria of gestational diabetes which best predicted adverse pregnancy outcome, future study should also scrutinise on the optimal glycaemic threshold, either in screening or diagnostic test, that relate to the mothers’ and children offspring’s long term cardiometabolic risk. / Tam, Wing Hung. / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 119-146). / Abstract also in Chinese. / LIST OF TABLES --- p.xxii / LIST OF FIGURES --- p.xxv / LIST OF ABBREVIATIONS --- p.xxvi / Chapter Chapter 1 --- Gestational diabetes & future cardiometabolic risk - an overview / Chapter 1.1 --- Historical background --- p.2 / Chapter 1.2 --- Pregnancy physiology vs. gestational diabetes --- p.5 / Chapter 1.3 --- Diabetes mellitus - a global epidemic --- p.6 / Chapter 1.4 --- History of gestational diabetes & progression to Type 2 DM --- p.7 / Chapter 1.5 --- History of gestational diabetes & cardiometabolic risk --- p.8 / Chapter 1.6 --- Type 2 DM among children and adolescents --- p.9 / Chapter 1.7 --- Type 2 DM among offspring of mothers with gestational diabetes --- p.10 / Chapter 1.8 --- Cardiometabolic risk in children exposed to maternal gestational diabetes --- p.12 / Chapter 1.9 --- Long term follow up on mothers & children cohort --- p.12 / Chapter Chapter 2 --- Research methodology / Chapter 2.1 --- Subjects --- p.16 / Chapter 2.2 --- Obstetric and neonatal information --- p.18 / Chapter 2.2.1 --- Maternal glycaemic indices at pregnancy --- p.18 / Chapter 2.2.2 --- Umbilical cord blood C-peptide & insulin levels --- p.18 / Chapter 2.2.3 --- Definition of antenatal variables --- p.19 / Chapter 2.3 --- Follow up assessment of the mothers --- p.19 / Chapter 2.4 --- Follow up assessment of the children and adolescents --- p.22 / Chapter 2.5 --- Definition of abnormal glucose tolerance and metabolic syndrome --- p.24 / Chapter 2.5.1 --- Definition of abnormal glucose tolerance --- p.24 / Chapter 2.5.2 --- Definition of metabolic syndrome in adult --- p.24 / Chapter 2.5.3 --- Definition of metabolic syndrome in adolescent --- p.25 / Chapter 2.6 --- Determination of insulin resistance and pancreatic beta cell function --- p.26 / Chapter 2.6.1 --- Definition of insulin resistance --- p.26 / Chapter 2.6.2 --- Definition of pancreatic beta cell function --- p.26 / Chapter 2.6.3 --- Measurement of insulin resistance and pancreatic β-cell function --- p.27 / Chapter 2.7 --- Statistical analysis --- p.31 / Chapter 2.7.1 --- Statistical programme --- p.31 / Chapter 2.7.2 --- Comparison between group differences --- p.31 / Chapter 2.7.3 --- General Linear Model --- p.32 / Chapter 2.7.4 --- Multivariate logistic regression --- p.33 / Chapter 2.7.5 --- Receiver operating characteristic analysis --- p.37 / Chapter 2.8 --- Ethics approval --- p.41 / Chapter 2.9 --- Funding --- p.42 / Chapter Chapter 3 --- History of gestational diabetes and women’s future cardiometabolic risk / Chapter 3.1 --- Maternal clinical parameters at the index pregnancy --- p.44 / Chapter 3.2 --- Maternal cardiometabolic status at 8 years post-delivery --- p.45 / Chapter 3.3 --- Maternal cardiometabolic status at 15 years post-delivery --- p.49 / Chapter 3.4 --- Prediction of cardiometabolic risk by maternal gestational diabetic status --- p.50 / Chapter 3.4.1 --- Abnormal glucose tolerance and metabolic syndrome at 8 years by maternal gestational diabetic status --- p.52 / Chapter 3.4.2 --- Abnormal glucose tolerance, DM, hypertension and metabolic syndrome at 15 years by maternal gestational diabetic status --- p.52 / Chapter 3.5 --- The role of insulin resistance in predicting women’s DM and metabolic syndrome --- p.55 / Chapter 3.6 --- Discussion --- p.57 / Chapter 3.7 --- Conclusion --- p.62 / Chapter Chapter 4 --- Glycaemic variables measured at mid-gestation of the index pregnancy predict women’s future cardiometabolic risk / Chapter 4.1 --- Glycaemic levels in pregnancy and perinatal outcome --- p.64 / Chapter 4.2 --- Glycaemic levels in pregnancy and women’s future cardiometabolic risk --- p.65 / Chapter 4.2.1 --- Prediction of women’s cardiometabolic risk at 8 and 15-year --- p.66 / Chapter 4.2.2 --- Optimal cut-off levels in predicting women’s future cardio- metabolic risk --- p.69 / Chapter 4.3 --- Discussion --- p.75 / Chapter 4.4 --- Conclusion --- p.78 / Chapter Chapter 5 --- Maternal gestational diabetes and offspring’s cardiometabolic risk / Chapter 5.1 --- Offspring’s cardiometabolic risk at 8 years age --- p.80 / Chapter 5.1.1 --- Baseline characteristics at pregnancy and delivery --- p.80 / Chapter 5.1.2 --- Children’s clinical and biochemical parameters at 8 years age --- p.82 / Chapter 5.2 --- Offspring’s cardiometabolic risk at 15 years age --- p.84 / Chapter 5.2.1 --- Adolescents’ clinical and biochemical parameters at 15 years age --- p.84 / Chapter 5.2.2 --- Clinical parameters of adolescents with abnormal glucose tolerance --- p.84 / Chapter 5.3 --- Discussion --- p.88 / Chapter 5.4 --- Conclusion --- p.90 / Chapter Chapter 6 --- In utero hyperinsulinaemia and offspring’s cardiometabolic risk / Chapter 6.1 --- Umbilical cord blood insulin and C-peptide --- p.92 / Chapter 6.1.1 --- Umbilical cord insulin and C-peptide concentrations in the original cohort --- p.92 / Chapter 6.1.2 --- Determination of in utero hyperinsulinaemia by umbilical cord insulin and C-peptide levels --- p.95 / Chapter 6.2 --- The effect of in utero hyperinsulinaemia on children’s abnormal glucose tolerance at 8 years of age --- p.98 / Chapter 6.2.1 --- Receiver operating characteristic analysis --- p.98 / Chapter 6.2.2 --- Logistic regression analysis --- p.98 / Chapter 6.3 --- The effect of in utero hyperinsulinaemia on adolescents’ cardio- metabolic risk at 15years of age --- p.102 / Chapter 6.3.1 --- Logistic regression analysis --- p.102 / Chapter 6.4 --- Discussion --- p.105 / Chapter 6.5 --- Conclusion --- p.108 / Chapter Chapter 7 --- Summary and conclusion / Chapter 7.1 --- Summary of the thesis --- p.110 / Chapter 7.1.1 --- Women’s long term cardiometabolic risk after a pregnancy with gestational diabetes --- p.110 / Chapter 7.1.2 --- The long term cardiometabolic risk of children born to mothers who had gestational diabetes --- p.111 / Chapter 7.1.3 --- New findings from the studies and their implications --- p.111 / Chapter 7.2 --- Strength and weakness in the study --- p.113 / Chapter 7.2.1 --- Unique cohort from universal screening --- p.113 / Chapter 7.2.2 --- Study design --- p.113 / Chapter 7.2.3 --- Response rate and loss to follow up --- p.114 / Chapter 7.2.4 --- Treatment effect of gestational diabetes --- p.115 / Chapter 7.3 --- Issues of future research --- p.115 / Chapter 7.3.1 --- Follow up study on the HAPO cohort --- p.115 / Chapter 7.3.2 --- Opportunity for international collaboration --- p.117 / Chapter 7.4 --- Conclusion --- p.118 / REFERENCES --- p.119

Apolipoprotein E (apoE) is a lipid transport protein which plays a key role in lipid metabolism. In addition to the well known polymorphic coding alleles epsilon2, epsilon3 and epsilon4, APOE promoter single nucleotide polymorphisms (SNPs) have also been reported to modify disease susceptibilities in humans. / In a case-control study involving 710 Chinese type 2 diabetes and 198 non-diabetic subjects, genotyping of three SNPs (-491A/T, -219G/T and +113G/C) within the APOE proximal promoter identified that -491A was associated with increased risk for type 2 diabetes in women (OR=2.44, 95%CI=1.15-5.19, p=0.017). However, the three tested SNPs were not associated with the risk of diabetic nephropathy (DN). Yeast one-hybrid screening of the human brain cDNA library using the polymorphic DNA sequences spanning the APOE promoter -491 site as the 'baits' identified one of the interacting transcription factors being the activating transcription factor 4 (ATF4). Electrophoretic-mobility-shift assay confirmed the physical interaction of the purified recombinant ATF4 protein and APOE promoter -491 A/T spanning region (-521 to -461). The binding of ATF4 to the -491T-containing sequence was stronger than that of the -491A-containing sequence. Chromatin immunoprecipitation (ChIP) assay further confirmed the interaction between ATF4 and APOE promoter -491-spanning region in vivo. The functional significance of APOE -491A/T polymorphism was supported by the dual-luciferase reporter assay showing that -491 A to T single nucleotide substitution significantly decreased the activity of the cloned APOE promoter (-1019 to +407) in human kidney (293), liver (WRL-68) and astrocyte (U-87) cell lines. Further analysis showed that ATF4 over-expression significantly down-regulated the activities of the cloned APOE promoter. The suppression of ATF4 on APOE promoter with -491A allelic form was significantly stronger than that with -491T allelic form in 293 cells (p&lt;0.05). Interestingly, overexpression of recombinant ATF4 stimulated endogenous APOE transcription by about 10% in WRL-68 cells. / In conclusion, APOE promoter -491A/T polymorphism modifies the risk of type 2 diabetes in Hong Kong Chinese women. The -491A/T polymorphism controls APOE promoter activity and is interactive with transcription factor ATF4. / My thesis project aimed at testing two hypotheses: (1) APOE promoter SNPs associate with the risks of type 2 diabetes and diabetic nephropathy, (2) APOE promoter SNPs modify transcriptional control of the gene. / Geng, Hua. / "September 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4559. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 140-151). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.