Modelling methodologies to assess glucose metabolism in type 2 diabetes

• Main Author: Albarrak, Ahmed I.
• Published: City, University of London 2003
• Subjects: 616; R Medicine
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274525

The aetiology and pathogenesis of type 2 diabetes (T20) are yet to be fully understood. However, there is a degree of agreement that the most important pathological factors of T20 are p-cell dysfunction and insulin resistance. Moreover T2D is characterised by varying degrees of impaired pancreatic p-cell responsiveness and/or insulin resistance. The ability to easily quantify insulin sensitivity is useful for investigating the role of impaired insulin secretion and action in the pathophysiology ofT2D. The current work provided novel knowledge in both clinical and methodological areas. On the clinical side, it provided new information about pathology of T2D. On the methodological side, it assessed validity, performance, and/or reproducibility of two powerful models to assess insulin responsiveness and sensitivity. The aim was to use modelling techniques employing data collected during tolerance tests to progress our understanding of pathology of type 2 diabetes. This research evaluated and/or validated two approaches namely, the insulin secretion model and the minimal model, respectively, to assess pancreatic p-cell responsiveness and insulin sensitivity. These methods were then applied to study the aetiology and pathology of T2D on its first clinical appearance (newly diagnosed SUbjects). The insulin secretion model was assessed with two reduced sampling schemes. The model was validated during the oral glucose tolerance test (OGTT). and its performance was compared during OGTT and the meal tolerance test (Mm). The reproducibility of the model indices was also assessed during MTT and OGTT. The one and two compartmental minimal model performance was evaluated and compared to the clamp in subjects with T20. The insulin secretion model and the one compartment minimal model were then applied to study newly presenting T2D in order to gain more understanding of the disease pathology. The output results showed the ability of these approaches to explain the inter-individual variability of important glucose clinical measures such as FPG and HbA1C• In conclusion the insulin secretion model and the one compartment minimal model demonstrated their validity and utility in assessing insulin sensitivity and p-cell responsiveness to provide better Wlderstanding of type 2 diabetes.