City Research Online

Abstract

The development of type 2 diabetes (T2D) is a gradual process, and the relative roles of impaired insulin secretion and resistance in aetiology of the disease remain controversial. However, it is widely recognised that both defects are present in all overt subjects with T2D.

The current work provides new knowledge on both methodological and pathophysiolog-ical levels related to T2D. On the methodological level, a population-based approach, Bayesian hierarchical analysis (BAY), developed and was used to estimate parame-ters of the minimal model of glucose kinetics using data collected in newly presenting T2D subjects to investigate insulin sensitivity and glucose effectiveness. BAY results were compared with the standard two-stage approach, which employs the non-linear regression analysis. BAY was also employed to derive and compare estimates of insulin sensitivity and glucose effectiveness with a full sample scheme (30 points) with those estimated with 12 and 13 sample schemes.

The results demonstrated that BAY, besides avoiding parameter estimation failures, gives a smaller unbiased estimate of the population variance for both insulin sensitivity and glucose effectiveness. The analysis of reduced sampling schemes with BAY sug-gested that the adoption of the 13 sample scheme is preferable to that of the 12 sample scheme.

On the pathophysiological level, BAY was employed in combination with other tech-niques to increase understanding of early progression of T2D. The research investigated the progression of insulin sensitivity and insulin secretion over 2 years after diagnosis of T2D and relationships with clinical measures of glucose control.

The results demonstrated that /3-cell function can be ameliorated for at least two years by adequate conventional treatments after diagnosis of T2D. The improvement in gly-cated haemoglobin (HbAic) in the earlier years of T2D are associated with improved fasting and postprandial insulin pancreatic responsiveness. The results showed that the ability of indices of insulin sensitivity and pancreatic /3-cell responsiveness to explain inter-individual variability of measures of glucose control in newly presenting T2D de-crease over time for clinical measures of glucose control, and measures of glucose and insulin responses to the meal tolerance test.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > QA Mathematics Q Science > QH Natural history > QH301 Biology R Medicine
Departments:	School of Science & Technology School of Science & Technology > School of Science & Technology Doctoral Theses Doctoral Theses

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