Type-2 diabetes is one of the most prevalent non-communicable diseases globally. The prevalence has increased rapidly in both developed and developing countries. Type-2 diabetes has become epidemic in China in the past three decades. With a relatively low obesity prevalence compared to western countries, such as the United States, the question has arisen as to why people in China are so susceptible to diabetes, but few studies have answered this question definitively. Asians have lower muscle mass than Caucasians which could be one possible explanation. This study aims to test the hypothesis that pubertal muscle mass acquisition, under the influence of testosterone, may be a risk factor for diabetes. This study recruited from the population-representative Chinese “Children of 1997” birth cohort with 8327 participants (88% of all infants born in April and May 1997) in Hong Kong. Participants were aged 15 years at the time of this study. The main objective was to examine the association of pubertal muscle mass with diabetes risk factors, and to examine determinants of pubertal muscle mass in this non-western setting. In June to August 2012, 502 participants from “Children of 1997” were recruited to complete a health assessment follow up at the Active Health Clinic in University of Hong Kong, including a questionnaire, blood tests and a physical examination. Multivariable linear regression was used to assess the associations of: (1) testosterone and pubertal muscle mass with diabetes risk factors, including fasting glucose, fasting insulin and homeostasis model assessment -insulin resistance (HOMA-IR), and any mediation of the association of testosterone with diabetes risk factors by pubertal muscle mass, and (2) environmental influences, including intergenerational influences, proxied by mother’s place of birth, and current life style influences (meat consumption and physical activity), with pubertal muscle mass. Higher pubertal testosterone was associated with lower fasting glucose (-0.008, 95% confidence interval (CI) -0.015 to -0.002), fasting insulin (-0.44, 95% CI -0.57 to -0.31) and HOMA-IR (-0.090, 95% CI -0.12 to -0.063) after adjusting for potential confounders, i.e, sex, birth weight, highest parental education, mother’s place of birth and physical activity. The association was partially mediated by skeletal muscle mass and body fat percentage. Skeletal muscle mass was negatively associated with fasting glucose (-0.017, 95% CI -0.025 to -0.009), insulin (-0.876, 95% CI -1.033 to -0.719), and HOMA-IR (-0.180, 95% CI -0.214 to -0.147) after adjusted for potential confounders. High meat consumption (0.176, 95% CI 0.000 to 0.351) and physical activity (0.157, 95% CI 0.059 to 0.254) were both associated with higher skeletal muscle mass in adolescents; however birth weight and mother’s place of birth had no influence on pubertal skeletal muscle composition. Higher pubertal muscle mass and testosterone are association with better glucose metabolism in adolescence. Food intake and physical activity may also influence the development of skeletal muscle, thus adolescence may be a sensitive period for the development of diabetes where interventions to increase muscle mass could have long-term protective effects. / published_or_final_version / Public Health / Master / Master of Philosophy

published_or_final_version / abstract / Medicine / Master / Doctor of Medicine

The main study purposes were to determine: whether antidepressant (AD) use increases the risk of type 2 diabetes mellitus; and whether results differ when using different methodological designs: retrospective cohort design and nested case-control design. A retrospective Texas Medicaid database analysis of new AD (exposed cohort) and benzodiazepine (unexposed cohort [BZ]) users from January 1, 2002 to December 31, 2009 was conducted. Patients aged 18-64 years without diabetes at cohort entry were included. The primary outcome was incident diabetes and the main independent variable was AD vs. BZ use. Covariates included age, gender, race/ethnicity, medication adherence, persistence, number of concomitant diabetogenic medications, Chronic Disease Score, treatment duration, year of cohort entry, and use of both AD and BZ at index. Regression analyses (adjusted) were used to address the study purposes. Of the study cohort (N=44,715), 35,552 (79.5%) were AD users and 9,163 (20.5%) were BZ users. Patients were followed for an average of 2.3±1.9 years (Median=1.8 years), were on average 38.6±14.2 years old, and 69.3% were female. Using the retrospective cohort design, AD use was associated with a 48.9% increase (logistic regression) and 60.0% increase (Cox regression) in the risk of diabetes compared to BZ use (logistic regression analysis: RR[subscript adj]. =1.489; 95% CI: 1.331-1.667; Cox regression analysis: HR[subscript adj]. =1.600; 95% CI: 1.437 - 1.783). Using a nested case-control design within the entire study cohort, AD use was associated with a 54.1% increase in the risk of diabetes compared to BZ use (OR[subscript adj]. =1.541; 95% CI: 1.368 - 1.735). Using a nested case-control design within the exposed cohort, current AD use was associated with a two-fold higher risk of diabetes compared to former AD use (OR[subscript adj]. =1.995; 95% CI: 1.759 - 2.264). Among antidepressant classes, TCAs, SSRIs, SNRIs, and Other ADs were associated with a higher diabetes risk compared with BZs. The results from the present study suggest that AD use is associated with an increased risk of diabetes. Clinicians may need to take this into account when choosing treatment for depression in patients at high risk of diabetes. / text

Pregestational and gestational diabetes (GDM) places the mother and her offspring at an increased risk for later development of insulin resistance and type 2 diabetes. Oxidative stress may mediate long-term disturbances in glucose homeostasis associated with type 2 diabetes and the metabolic syndrome. This thesis describes a cross-sectional study examining serum concentrations of free radical generated oxysterols as markers of oxidative stress in a cohort of teenage daughters from pregnancies with and without GDM. Daughters of GDM-pregnancies had a tendency of higher levels of serum oxysterols (7beta-hydroxycholesterol); however, this difference was not statistically significant after adjustment for total cholesterol. Serum oxysterols were significantly correlated with obesity measures such as waist circumference and BMI, which likely accounted for the tendency for higher measures of oxysterol concentrations in the GDM daughters. Oxysterols represent potentially important biomarkers for oxidative stress in adolescent girls as their levels track with the metabolic syndrome risk factors. / Le diabète pré-gestationnel et le diabète de gestation (DG) augmentent le risque dedéveloppement d'une future résistance à l'insuline et de diabète de type 2 autant pourla mère que pour l'enfant. Le stress oxydatif est un facteur potentiel impliqué dans ledéséquilibre du glucose sanguin associé au diabète de type 2 et au syndromemétabolique. La présente thèse est une étude sectionnelle croisée, ayant pour but demesurer des marqueurs du stress oxidatif, notamment la concentration des oxystérolsgénérés par les radicaux libres dans le sérum d'adolescentes, nées de mères ayantprésenté ou non un diabète de gestation. Nos résultats montrent des concentrationsd'oxystérols (7P-hydroxycholesterol) plus élevées dans le sérum de filles issues degestations diabétiques à comparer aux filles de mères n'ayant pas eu de DG.Cependant, la différence entre les deux groupes n'était pas statistiquementsignificative après un ajustement au cholestérol total. La concentration d'oxystérolsétait significativement corrélée aux marqueurs d'obésité, notamment la circonférencede la taille et l'index de masse corporelle, possiblement à l'origine de la tendance desoxystérols à être plus élevés dans le cas des adolescentes issues de gestationsdiabétiques.

Inflammation contributes to the etiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Therefore, it is of interest to investigate how diet relates to plasma inflammatory proteins, particularly whole grain and fibre intakes, as these factors have been associated with lower CVD and T2D risk. Only a limited number of observational studies have examined these relationships. The objective of this study was to investigate the cross-sectional relationships of whole and refined grain and dietary fibre intakes with plasma inflammatory proteins. There was a strong inverse relationship between whole grain intake and plasminogen activator inhibitor type 1 (PAI-1) (β =-0.102; SE=0.038; p=0.0077), and a positive relationship between refined grain intake and PAI-1 (β=0.076; SE=0.034; p=0.0251). Additionally, dietary fibre was related to lower concentrations of C-reactive protein (β=-0.034; SE=0.010; p=0.0008) and fibrinogen (β=-1.207; SE=0.505; p=0.0171). This research suggests that whole and refined grain and fibre intakes may influence inflammatory protein concentrations.

Inflammation contributes to the etiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Therefore, it is of interest to investigate how diet relates to plasma inflammatory proteins, particularly whole grain and fibre intakes, as these factors have been associated with lower CVD and T2D risk. Only a limited number of observational studies have examined these relationships. The objective of this study was to investigate the cross-sectional relationships of whole and refined grain and dietary fibre intakes with plasma inflammatory proteins. There was a strong inverse relationship between whole grain intake and plasminogen activator inhibitor type 1 (PAI-1) (β =-0.102; SE=0.038; p=0.0077), and a positive relationship between refined grain intake and PAI-1 (β=0.076; SE=0.034; p=0.0251). Additionally, dietary fibre was related to lower concentrations of C-reactive protein (β=-0.034; SE=0.010; p=0.0008) and fibrinogen (β=-1.207; SE=0.505; p=0.0171). This research suggests that whole and refined grain and fibre intakes may influence inflammatory protein concentrations.

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Master of Public Health / OBJECTIVES: In Australia, diabetes causes significant morbidity and mortality. Whilst the need to prevent diabetes and its complications has been widely recognised, the capacity of health care systems - which organise diabetes care - to facilitate prevention has not been fully established. METHODS: A series of seven population-based case-control studies were used to examine the effectiveness of the Australian health care system and its capacity to manage diabetes. Six of the studies compared the patterns of care of patients who had developed advanced diabetes complications in 2000 (cases), to similar patients who remained free of the condition (controls) across Australia and for various risk groups. A secondary study investigated the role of treating GPs in the development of the outcome. RESULTS: A strong relationship between the patterns of care and the development of advanced diabetes complications was found and is described in Chapter 4. In Chapter 5, this same relationship was investigated for each Australian state and territory, and similar findings were made. The study in Chapter 6 investigated whether late diagnosis or the patterns of care was the stronger risk factor for advanced diabetes complications, finding that the greatest risk was associated with the latter. In Chapter 7 the influence of medical care during the pre-diagnosis period was explored, and a strong relationship between care obtained in this period and the development of advanced complications was found. In Chapter 8, which investigated the role of socio-economic status in the development of advanced complications, found that the risk of advanced diabetes complications was higher in low socio-economic groups. Chapter 9 investigated geographic isolation and the development of advanced diabetes complications and found that the risk of advanced complications was higher in geographically isolated populations. Finally, Chapter 10, which utilised a provider database, found that some GP characteristics were associated with the development of advanced diabetes complications in patients. CONCLUSION: A number of major risk factors for the development of advanced complications in Australia was found. These related to poorer diabetes management, later diagnosis, low socioeconomic status and geographic isolation. Strategies must be devised to promote effective diabetes management and the early diagnosis of diabetes across the Australian population.

Daughters of gestational diabetes (GDM) affected pregnancies are at greater risk for the development of type 2 diabetes mellitus (DM) later in life. Adiponectin is an early marker of DM risk. Dietary fat quality has been proposed to be involved in the development of insulin resistance. Plasma fatty acids are a marker of recent dietary exposure. The objectives of this research were to determine whether differences in adiponectin exist in daughters of GDM pregnancies, and to describe how dietary fatty acids impact adiponectin concentrations. Fasting adiponectin and plasma fatty acids were examined for 180 adolescent daughters born to mothers with and without GDM. No differences were observed in adiponectin between study groups, however; a significant difference was detected upon comparison of daughters from mothers who were presently diabetic with those from healthy mothers. The association between fatty acids and adiponectin varied by visceral adiposity. Adiponectin was inversely associated with monounsaturated and omega-3 (n-3) fatty acids in the high waist group. Further knowledge on the interactions between fatty acids, desaturase activity and adiponectin would be helpful in planning early interventions for individuals at risk for diabetes.

Master of Public Health / OBJECTIVES: In Australia, diabetes causes significant morbidity and mortality. Whilst the need to prevent diabetes and its complications has been widely recognised, the capacity of health care systems - which organise diabetes care - to facilitate prevention has not been fully established. METHODS: A series of seven population-based case-control studies were used to examine the effectiveness of the Australian health care system and its capacity to manage diabetes. Six of the studies compared the patterns of care of patients who had developed advanced diabetes complications in 2000 (cases), to similar patients who remained free of the condition (controls) across Australia and for various risk groups. A secondary study investigated the role of treating GPs in the development of the outcome. RESULTS: A strong relationship between the patterns of care and the development of advanced diabetes complications was found and is described in Chapter 4. In Chapter 5, this same relationship was investigated for each Australian state and territory, and similar findings were made. The study in Chapter 6 investigated whether late diagnosis or the patterns of care was the stronger risk factor for advanced diabetes complications, finding that the greatest risk was associated with the latter. In Chapter 7 the influence of medical care during the pre-diagnosis period was explored, and a strong relationship between care obtained in this period and the development of advanced complications was found. In Chapter 8, which investigated the role of socio-economic status in the development of advanced complications, found that the risk of advanced diabetes complications was higher in low socio-economic groups. Chapter 9 investigated geographic isolation and the development of advanced diabetes complications and found that the risk of advanced complications was higher in geographically isolated populations. Finally, Chapter 10, which utilised a provider database, found that some GP characteristics were associated with the development of advanced diabetes complications in patients. CONCLUSION: A number of major risk factors for the development of advanced complications in Australia was found. These related to poorer diabetes management, later diagnosis, low socioeconomic status and geographic isolation. Strategies must be devised to promote effective diabetes management and the early diagnosis of diabetes across the Australian population.