published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Social Work / Master / Master of Social Work

published_or_final_version / Pathology / Master / Master of Philosophy

published_or_final_version / Public Health / Master / Master of Public Health

Background and objectives: Recent genome-wide association (GWA) studies conducted in Caucasian populations have significantly expanded the list of confirmed and potential susceptibility genes for obesity and type 2 diabetes. The major objective of this thesis was to establish the role of the previously identified obesity- and T2DM-susceptibility genes in the Hong Kong Southern Chinese population. Major findings: In a cross-sectional case-control study of Southern Chinese which involved 470 obese cases and 700 normal-weight controls, significant associations with obesity were demonstrated in 7 of 13 single nucleotide polymorphisms (SNPs) that have shown significant associations with obesity and/or body mass index (BMI) in previous Caucasian GWA studies. These SNPs are located within or near the GNPDA2, FTO, MC4R, KCTD15, SFRS10-ETV5-DGKG, SEC16B-RASAL2 and NEGR1 loci. The combined genetic risk score (GRS) of the 13 studied SNPs was associated with an increased risk for obesity. The GNPDA2 rs10938397, FTO rs8050136, and MC4R rs17782313, which showed the most significant associations with obesity, were further examined for their associations with persistent central obesity and the metabolic syndrome (MetS). Both rs8050136 and rs10938397 were significantly associated with persistent central obesity. rs10938397 was also associated with the MetS. The combined GRS of these 3 SNPs showed significant associations with both persistent central obesity and persistent MetS. Nineteen multimarker-tagging SNPs that span a well-defined LD block of the FTO gene were evaluated for their associations with obesity in a case-control study which involved 249 cases and 400 controls. rs16952522 was found to be significantly associated with obesity, in addition to the well-known SNP rs8050136. These 2 SNPs were nominally associated with T2DM, although the associations were abolished after adjustment for age, sex and BMI. However, the GA haplotype composed of the risk alleles of these 2 SNPs was significantly associated with T2DM, independent of BMI. Seventeen previously identified T2DM-associated SNPs were investigated for the associations with glycaemic progression in an 8-year follow-up study which involved 518 cases and 998 controls. Their combined GRS was associated with an increased risk for glycaemic progression. A significant association with glycaemic progression was found with CDKN2A/B rs10811661. Moreover, KCNJ11 rs5219 and IGF2BP2 rs11711477 also showed potential associations with glycaemic progression. In the subsequent 12-year follow-up study, which involved 200 cases and 903 controls, the CDKN2A/B rs10811661 showed a significant independent association with incident T2DM. The KCNJ11 E23K (rs5219) variant was examined for its association with diabetes development in a 12-year prospective study. It was found to be significantly associated with the development of prediabetes but not with the development of T2DM. However, in a meta-analysis which involved 15680 subjects across different populations, this variant could indeed predict T2DM. Conclusions: The findings of this thesis have provided novel evidence supporting the role of the GWA studies-identified obesity- and T2DM-associated genetic variants as genetic markers of obesity and T2DM among Southern Chinese in Hong Kong, and suggest that the GNPDA2, FTO and MC4R genes confer susceptibility to obesity and that the CDKN2A/B and KCNJ11 genes may play a role in diabetes development. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Background. With increasing personal affluence and changes in lifestyle, there is rising prevalence of type 2 diabetes mellitus in Hong Kong. Approximately 60% of diabetic subjects in Hong Kong are asymptomatic and previously undiagnosed. Since diabetes carries significant mortality and morbidity risk, it is important to diagnose these subjects early for intervention. There are many known factors associated with development of type 2 diabetes. Some are remediable such as obesity, dyslipidaemia, hypertension, while some are non-remediable such as age and past history of gestational diabetes. Identifying high-risk subjects will increase the yield and cost-effectiveness of screening program for diabetes and related risk factors and provide useful epidemiological information on the natural history of these diseases. / Methods. I used data from several cross-sectional and prospective studies of which I was the principal investigator or one of the co-investigators to test these hypotheses. The studies include mainly the following: (1) A public utility company workforce survey on cardiovascular risk factors in 1990 (n=1513). (2) Chinese subjects with risk factors for diabetes who underwent 75 gram oral glucose tolerance test (OGTT) screening at the Prince of Wales Hospital (PWH) between 1988 and 1995 (n=3718). (3) The 'United Christian Nethersole Community Health Service' (UCNCHS) primary health screening program database in 1997 (n=17764). / Objectives & hypothesis. I aimed to study the various factors associated with the development of type 2 diabetes in Hong Kong Chinese. With this information, I can design a screening method to early identify those subjects who are at high-risk for diabetes. I hypothesize the following: (1) Many risk factors for diabetes in Caucasians are also applicable to Hong Kong Chinese. (2) The presence of multiple factors increases the risk of diabetes in a linear fashion. (3) Chinese subjects are at risk of developing diabetes at a lower threshold of obesity, which is one of the most important risk factors for type 2 diabetes. / Results. Based on a cohort of 1513 asymptomatic subjects from a workforce survey, those in the top quartile of body mass index (BMI), as compared to those in the lowest quartile, had a 4 to 10-fold increased risk of diabetes and a 2.5 to 5-fold increased risk of impaired glucose tolerance (IGT) for men and women. (Abstract shortened by UMI.) / Ko Tin Choi. / "May 2005." / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0173. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 264-283). / 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. / School code: 1307.

Fok, Tsz Nam = 香港二型糖尿病併發症風險評估模型 / 霍梓楠. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (p. 71-72). / Abstracts in English and Chinese. / Fok, Tsz Nam = Xianggang er xing tang niao bing bing fa zheng feng xian ping gu mo xing / Huo Zinan. / Abstract --- p.i / 概要 --- p.iii / Acknowledgements --- p.iv / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Dataset Information --- p.3 / Chapter 3 --- Background and Literature Review --- p.9 / Chapter 3.1 --- The Idea of Risk Model --- p.9 / Chapter 3.2 --- Discrimination Problem --- p.10 / Chapter 3.3 --- Receiver Operating Characteristic (ROC) Curve --- p.11 / Chapter 3.4 --- Summary Indices of the ROC Curve --- p.13 / Chapter 3.4.1 --- Area Under ROC Curve (AROC) --- p.14 / Chapter 3.4.2 --- Maximum Vertical Distance --- p.16 / Chapter 3.5 --- Discrimination Performance in Prognostic Model --- p.18 / Chapter 3.5.1 --- Survival Data --- p.18 / Chapter 3.5.2 --- Survival Function --- p.20 / Chapter 3.5.3 --- Time-dependent ROC Curve for Censored Data --- p.21 / Chapter 3.6 --- Earlier Work on Diabetic Complications Risk Models --- p.22 / Chapter 3.6.1 --- Maximization of the AROC --- p.28 / Chapter 4 --- Model Development --- p.29 / Chapter 4.1 --- Overview --- p.29 / Chapter 4.2 --- Estimating the ROC curve and the AROC --- p.29 / Chapter 4.3 --- Choosing Suitable Risk Factors --- p.30 / Chapter 4.4 --- Mixing Risk Factors and Optimizing Coefficients --- p.31 / Chapter 4.5 --- Validation of Risk Equations Using Test Set --- p.33 / Chapter 5 --- Results and Validation --- p.34 / Chapter 5.1 --- Performance of the Risk Factor Candidates --- p.34 / Chapter 5.2 --- Estimation of the Coefficients --- p.37 / Chapter 5.3 --- Checking the Uniqueness of the Solution --- p.41 / Chapter 5.4 --- Validation Using Test Set --- p.46 / Chapter 5.5 --- Comparison of AROC-optimized and MVD-optimized Risk Equations --- p.56 / Chapter 6 --- Comparison of our Results with Earlier Work --- p.58 / Chapter 7 --- "Discussion, Outstanding Issues and Future Works" --- p.66 / Chapter 7.1 --- Comparison Between the AROC and the MVD --- p.66 / Chapter 7.2 --- Applications of Risk Models --- p.68 / Chapter 7.3 --- Limitations of the study --- p.69 / Chapter 7.4 --- Outstanding Issues and Future Works --- p.69 / Chapter 7.4.1 --- The Estimation of Error Due to Sampling Variance --- p.69 / Chapter 7.4.2 --- Time-dependent Coefficients --- p.69 / Chapter 7.4.3 --- Extending the Idea to other Datasets --- p.70 / Chapter 7.5 --- Conclusion --- p.70 / Bibliography --- p.71

Chan Siu-Wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 173-200). / Abstracts in English and Chinese; appendix in Chinese. / Table of Contents --- p.i / Abstract --- p.v / 論文摘要 --- p.ix / Acknowledgments --- p.xii / Table of Figures --- p.xiii / Table of Tables --- p.xvii / Chapter Chapter 1. --- Introduction --- p.1 / Chapter Chapter 2. --- Literature Review --- p.3 / Chapter 2.1 --- Diabetes Mellitus (DM)： Overview --- p.3 / Chapter 2.1.1 --- Diagnosis and Diagnostic Criteria --- p.4 / Chapter 2.1.2 --- Classifications of Diabetes Mellitus --- p.8 / Chapter 2.1.3 --- Management of Type 2 Diabetes Mellitus --- p.15 / Chapter 2.2 --- Diabetes Mellitus Complications： Overview --- p.25 / Chapter 2.2.1 --- Microvascular Complications --- p.26 / Chapter 2.2.2 --- Macrovascular Complications --- p.31 / Chapter 2.3 --- Type 2 Diabetes Mellitus - A Rising Global Burden --- p.32 / Chapter 2.3.1 --- Prevalence of Type 2 Diabetes Mellitus --- p.32 / Chapter 2.3.2 --- Prevalence of Type 2 Diabetes Mellitus in Hong Kong --- p.36 / Chapter 2.3.3 --- Mortality and Morbidity of Type 2 Diabetes Mellitus in Hong Kong --- p.40 / Chapter 2.4 --- cost of Type 2 Diabetes Mellitus - Under-explored Area in Hong Kong and Asia --- p.46 / Chapter 2.4.1 --- Cost of Type 2 Diabetes Mellitus in the USA --- p.48 / Chapter 2.4.2 --- Cost of Type 2 Diabetes Mellitus in Europe --- p.57 / Chapter 2.4.3 --- Cost of Type 2 Diabetes Mellitus in Asia-Pacific --- p.61 / Chapter 2.5 --- Hong Kong Healthcare System --- p.65 / Chapter 2.5.1 --- Hospital Authority in Hong Kong (Public Healthcare Sector) --- p.67 / Chapter 2.5.2 --- Hong Kong Healthcare Financing System --- p.73 / Chapter 2.6 --- New Emerging Drug Treatment for Type 2 DM in Hong Kong Chinese - Rosiglitazone --- p.77 / Chapter 2.6.1 --- Clinical Efficacy and Tolerability of Rosiglitazone --- p.77 / Chapter 2.6.2 --- Cost-effectiveness of Rosiglitazone --- p.78 / Chapter Chapter 3. --- Hypothesis and Objectives --- p.81 / Chapter 3.1 --- Cost of Type 2 Diabetes Mellitus in Hong Kong Chinese --- p.81 / Chapter 3.1.1 --- Hypothesis --- p.81 / Chapter 3.1.2 --- Objectives --- p.81 / Chapter 3.2 --- Cost-effectiveness Analysis of Metformin + Rosiglitazone vs. Metformin + Glibenclamide for Type 2 DM Patient Whose Diabetes is not Adequately Controlled by Metformin Alone from a Payer's Perspective --- p.82 / Chapter 3.2.1 --- Hypothesis --- p.82 / Chapter 3.2.2 --- Objectives --- p.83 / Chapter Chapter 4. --- Cost of Type 2 Diabetes Mellitus in Hong Kong Chinese --- p.84 / Chapter 4.1 --- Subjects and Methods --- p.84 / Chapter 4.1.1 --- Subjects --- p.84 / Chapter 4.1.2 --- Methods --- p.85 / Chapter 4.1.3 --- Validity and Reliability of the Chinese Questionnaire --- p.96 / Chapter 4.2 --- Results --- p.96 / Chapter 4.2.1 --- Subjects' Characteristics --- p.96 / Chapter 4.2.3 --- Comorbidity --- p.102 / Chapter 4.2.4 --- Complications --- p.102 / Chapter 4.2.5 --- Costs of Type 2 DM --- p.104 / Chapter 4.3 --- Discussions --- p.123 / Chapter Chapter 5 --- Cost-effectiveness Analysis of Metformin + Rosiglitazone vs. Metformin + Glibenclamide for Type 2 DM Patient Whose Diabetes is not Adequately Controlled by Metformin Alone from a Payer's Perspective --- p.134 / Chapter 5.1 --- Methods --- p.134 / Chapter 5.1.1 --- Model Overview --- p.134 / Chapter 5.1.2 --- "Success, Failure and Discontinuation Rates" --- p.138 / Chapter 5.1.3 --- Resources Use and Costs --- p.142 / Chapter 5.1.4 --- Health-Related Quality of Life (HRQOL) --- p.148 / Chapter 5.1.5 --- Base Case Analysis --- p.149 / Chapter 5.1.6 --- Sensitivity Analyses --- p.149 / Chapter 5.2 --- Results --- p.150 / Chapter 5.2.1 --- Base Case Model - CE Analysis: cost per controlled Type 2 DM patient --- p.150 / Chapter 5.2.2 --- Sensitivity Analysis- CE Analysis: cost per controlled Type 2 DM patient --- p.151 / Chapter 5.2.3 --- Base Case Model - CE Analysis: cost per EQ5D utility score --- p.154 / Chapter 5.2.4 --- Sensitivity Analysis- CE Analysis: cost per EQ5D utility score --- p.155 / Chapter 5.3 --- Discussions --- p.158 / Chapter Chapter 6. --- Conclusions --- p.163 / Appendix --- p.165 / References