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Arthur Sherman : Diabetes Pathogenesis as a Threshold-Crossing Process

It has long been accepted that type 1 diabetes results from a lack of insulin, as the insulin-secreting pancreatic beta cells are destroyed by an autoimmune process. In contrast, the cause of type 2 diabetes (T2D) is less clear. Most people with pre-diabetes or in the early stages of T2D have abnormally high plasma insulin concentrations, and insulin rises before glucose does. We show that these difficulties are resolved by a mathematical model in which the onset of T2D is represented by the crossing of a threshold. The threshold is atypical in some respects and requires consideration of the slow manifolds to avoid incorrect conclusions.

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