A mathematical model for a subtype of diabetes suggests the existence of multiple pancreatic β-cell inactivation mechanisms

Type 2 diabetes (T2D) is one of the most common chronic diseases in the world. Recently, T2D is increasingly recognized as heterogeneous, with different T2D patients experiencing a wide variation in the course of disease. This heterogeneity likely reflects underlying variations in the mechanisms driving disease progression (pathogenesis). In this work, we develop a mathematical model of the pathogenesis of Ketosis-prone diabetes (KPD), a subtype of T2D which shows rapid onset and partial remission upon treatment, in contrast to the typically slow and hard-to-reverse progression of T2D. We show that by adding a new process, where high glucose reversibly deactivates insulin-secreting cells, to an existing model of T2D pathogenesis, we can account for the phenomenology of KPD. This suggests that KPD is distinguished from “typical” T2D by the presence of such a process, and leads to predictions which will allow the model to be tested in future clinical studies.