Orientador: Cláudia Regina Lima Duarte da Silva. / Coorientador: Deisi Maria Vargas. / Dissertação (Mestrado Profissional em Saúde Coletiva) - Programa de Pós-Graduação em Saúde Coletiva, Centro de Ciências da Saúde, Universidade Regional de Blumenau, Blumenau.

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.

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.

[Truncated abstract] Type 1 Diabetes is emerging as a significant public health problem faced by nearly every country in the world. It has major economic and social implications with considerable burden of illness. Approximately 140,000 Australians have been diagnosed with T1DM with an annual increase in incidence rate of 3% per year, comparable to the overall global increase. The management of T1DM requires insulin therapy which places considerable burden on the patient and their carers. Coping with daily insulin injections, dietary changes, modification of physical activity and vigilant monitoring of blood glucose levels, will impact on patient?s quality of life. The optimum goal for the treatment of type 1 diabetes is to safely achieve near-normal glycaemia and failure to maintain this goal accelerates the progression of the devastating long term complications of diabetes. Unfortunately attempts to achieve near normal glycaemia are limited by the risk of excessive lowering of blood glucose levels and hypoglycaemia remains a major barrier to strict glucose control of diabetes. In general this thesis focuses on two fundamental issues related to the epidemiology of severe hypoglycaemia. Namely, methodological consideration when analysing prospective observational data and application of the most robust methodology. A prospective open cohort study of the Princess Margaret Hospital diabetes clinic established in 1992, with 99% case ascertainment was used. This hospital is the only paediatric referral centre for type 1 diabetes and every child diagnosed in the state of Western Australia is treated at this centre. ... The results of this study showed that severe hypoglycaemia remains a major problem and recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycaemia. The study in chapter 7 investigates genetic risk factors related to severe hypoglycaemia. A significant relationship where the presence of the iv deletion (D) allele of the angiotensin-converting enzyme (ACE) increases risk of severe hypoglycaemia has been reported. This study concludes that the presence of D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia. In an attempt to optimize glycemic control, patients may suffer multiple episodes of severe hypoglycaemia which can adversely affect quality of life as well as educational and intellectual disadvantage. The study in chapter 8 investigates the factors related to recurrent severe hypoglycaemia. A rigorous and informative time-to-event approach is used to account for within child correlation, staggered enrolment and timevarying covariates. This allows important risk factors to change over time. Preschool children have an increased risk of experiencing recurrent severe hypoglycaemia. The findings of this thesis highlights the importance of selecting appropriate analytical methodology to identify risk factors associated with severe hypoglycaemia and also to dismiss factors that had previously been thought to be important. This will help in formulating management plans in order to limit the impact of severe hypoglycaemia.

Autoimmune diabetes is a disorder in which the (3-cells in the pancreatic islets of Langerhans are specifically destroyed resulting in absolute insulin deficiency; typically this is a childhood-onset disease, Type 1 Diabetes (T1D). Type 2 Diabetes (T2D) is a metabolic disorder usually developing in adults resulting from defects in insulin secretion and action. Latent Autoimmune Diabetes in Adults (LADA) is a form of diabetes that shares autoimmune disease pathology with T1D but a clinical presentation similar to T2D; LADA patients develop diabetes as adults (>25 years) and do not immediately require insulin treatment for survival. They are therefore often misdiagnosed with T2D. The aims of this work were to characterise immunological and genetic aspects of LADA using a large cohort collected from various patient repositories the United Kingdom to determine if it is a separate disease entity or an age-related extension of T1D. Both T1D and LADA are characterised by autoantibodies to the islet cell protein glutamic acid decarboxylase 65 (GADA) at diagnosis. The persistence and titre of GADA post-diagnosis in LADA was examined at 0.5, 3 and 6 years. GADA persisted in 93% of patients for 6 years; GADA litres decreased between 0.5 and 3 years post-diagnosis and either stabilised or increased again between 3 and 6 years. GADA titre was not associated with age at diagnosis, glycaemic control, β-cell function or other clinical features. GADA titre at 0.5 years was associated with a greater likelihood of requiring more intensive antihyperglycaemic therapy but did not predict therapy or insulin requirement at 3 and 6 years. Autoantibodies against IA-2 plus GADA compared to GADA alone at diagnosis predicted increased therapy requirement by 3 and 6 years and insulin requirement by 3 years postdiagnosis. Variants of the Human Leukocyte Antigen (HLA) genes DRB1 and DQB1, are associated with susceptibility for T1 D. An analysis of these variants in LADA (n = 378) revealed that the predisposing and protective variants in LADA are similar to those reported in T1D; DR3 (in linkage disequilibrium, LD with DQ2) and DR4 (in LD with DQ8) were the main predisposing variants whereas DR2 (in LD with DQ6) was most the protective against LADA. 85% of LADA patients possessed the DR3 and DR4 specificities, compared with 95% seen in T1D, suggesting a reduced predisposition in LADA compared with T1D. Synergistic effects of the DR3 and DR4 specificities occurred in LADA and the DRB1*0401 allele within the DR4 specificity was predisposing to disease, as seen in T1D. No other predisposing variants were identified in LADA. As reported for T1D, DR11, DR13, DQ5, DQ7 and DQ9 were protective against LADA; DQ6 was positively correlated with age at diagnosis. Association analysis of the insulin gene region in LADA (n = 400) showed that the variable number of tandem repeats (VNTR) locus primarily confers susceptibility to disease. Overall, the short Class I alleles predisposed to disease whereas longer Class III alleles conferred dominant protection, as reported in T1D. Fine-structure analysis showed that the Class I haplotypes 'IC+/ID+' and 'ID-' both conferred susceptibility for LADA - unlike in T1D, where the ID- haplotype has been reported to have protective effects. The Class III 'Protective' and Very Protective' haplotypes, conferred equal protection in LADA, as reported forTID. In conclusion; GADA persist post-diagnosis but are not markers for disease progression of LADA. Patterns of susceptibility at the HLA and insulin gene regions in LADA are similar to that reported for T1 D. LADA is likely to represent an age-related extension of T1D rather than a separate disease entity.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Canterbury, 2008. / Typescript (photocopy). Includes bibliographical references (leaves 263-313). Also available via the World Wide Web.

Thesis (M.S.)--University of Michigan, 1993.

Thesis (M.S.)--University of Michigan, 1991.

Thesis (M.S.)--University of Michigan, 1991.