Applied Mathematics Colloquium

Abstract: Type 2 diabetes (T2D) is generally thought to result from the combination of two metabolic defects, insulin resistance, which increases the level of insulin required to maintain glucose within the normal range, and failure of insulin-secreting pancreatic beta cells to compensate for the increased demand. We have built up a comprehensive mathematical model of progression to T2D. The dynamics of failure and compensation can be described on two-dimensional slow manifold to investigate the mechanisms of progression to diabetes. In addition, we have extended our mathematical model by adding daily meals and hepatic glucose production, which is helpful for studying the clinical implications. These enhancements allow us to look at the mechanistic defects that underlie observed pathologies such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). The model supports associations found in experiments between IFG and excess HGP and between IGT and peripheral insulin resistance. The model suggests how to personalize therapeutic approaches for subjects based on their underlying metabolic abnormalities.