The contribution of impaired glucose metabolism to cardiovascular disease and mortality in Australians
Creators: name: Barr, Elizabeth
Publisher: name: Monash University
Year: 2017
Subjects: Uncategorized

description: Diabetes and cardiovascular disease (CVD) together represent one of the greatest public health and economic burdens for the Australian population. There is strong evidence that diabetes increases the risk of CVD and mortality, and emerging evidence from overseas populations indicates that the risk of CVD and mortality extends below the threshold to diagnose diabetes. By analysing data from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, this thesis explored the relationships between hyperglycaemia and (i) all-cause mortality, (ii) CVD mortality, and (iii) CVD events, including myocardial infarction, stroke, percutaneous transluminal coronary artery angioplasty and coronary artery bypass surgery, and the extent to which these relationships were independent of other traditional CVD risk factors, including insulin sensitivity. The AusDiab study is a national prospective cohort study of 11,247 men and women aged 25 years and over which incorporated a 75 gm oral glucose tolerance test and three indices of blood glucose: fasting plasma glucose (FPG), two-hour post-load plasma glucose (2hPG) and haemoglobin A1c (HbA1c). The updated homeostasis model assessment was also used to calculate an index of insulin sensitivity (HOMA-%S). Data on all-cause and CVD mortality were obtained through data linkage with the National Death Index, and self-reported non-fatal CVD events were verified through medical record adjudication; the methods of which were validated by linking a cohort of AusDiab participants from Western Australia to the Western Australian Hospital Morbidity Database. Participants were followed for a median of five to six years, and the association between glucose metabolism, analysed as both continuous and categorical variables, and mortality and CVD were analysed with Cox proportional regression. The findings confirmed the strong association between previously diagnosed diabetes and all-cause mortality, CVD mortality and coronary heart disease, which was independent of traditional CVD risk factors. The risk for all-cause mortality and fatal or non-fatal myocardial infarction was also significantly increased among those with intermediate hyperglycaemia, although for CVD mortality, stronger associations were observed for impairments in FPG than 2hPG. In those without diagnosed diabetes, a continuous relationship between 2hPG and HbA1c and both all-cause and CVD mortality was observed. For FPG, the relationships were J-shaped, with the risks being increased at both high and low glucose concentrations. FPG was a better predictor of CVD mortality compared with 2hPG or HbA1c, but none of the glucose measures improved CVD risk prediction above that provided by traditional CVD risk factors. There was a continuous relationship between HOMA-%S and fatal or nonfatal CVD events, but this was mainly explained by its association with high-density lipoprotein cholesterol. FPG, but not HOMA-%S, significantly improved the prediction of CVD beyond that of other risk factors. Finally, a stronger relationship was observed between abnormal glucose metabolism and fatal or non-fatal myocardial infarction than with coronary artery revascularisation or stroke. Taken together, the findings of this thesis indicate that abnormal glucose metabolism, including both diabetes and intermediate hyperglycaemia, play an important role in the development of CVD, and suggest that CVD prevention strategies should not only target diabetes, but all levels of hyperglycaemia. <br>Awards: Winner of the Mollie Holman Doctoral Medal for Excellence, Faculty of Medicine, Nursing and Health Sciences, 2009.