Measuring β-cell function in vivo to understand the pathophysiology of type 2 diabetes

Abstract

Diabetes arises when insulin secretion is inadequate for the prevailing metabolic conditions. As such appropriate measurement of β-cell function is necessary for a better understanding of the pathophysiology of prediabetes and diabetes. Unfortunately this is not a straightforward process and requires utilization of mathematical modelling to best appreciate its complexities. This is because insulin concentrations in the plasma represent a balance between the processes of secretion, hepatic extraction and clearance. In isolation such simple measures reveal very little about β-cell function. Moreover, since insulin lowers glucose accounting for the effect of the former on the latter it is a key part of understanding insulin action. The development of the minimal model has allowed simultaneous measurement of the dynamic relationship between insulin secretion and insulin action and produces a quantitative number – the Disposition Index – which quantifies β-cell function. At present this remains the best functional measure of islet health, however, it may not capture other phenotypes such as β-cell senescence or the effect of incretin hormones on β-cell function. Future ongoing development and interaction with other technologies, such as functional imaging, should enhance the contribution of this functional testing to the prevention, treatment and understanding of type 2 diabetes.