Is High Insulin Protective or Detrimental?

We develop a model for progression to type 2 diabetes using longitudinal data from Southwest Native Americans. We then apply it to explain the accelerated disease progression in the small subset of the population who carry a variant in the ABCC8 gene, part of the KATP channel, that causes hypersecretion.Supplemental Method File S1 provides detailed descriptions of all modeling procedures, including Figures M1–M10, Tables M1–M9, and Models 1–5.2.1.Supplemental Material File S2 includes Figures S1–S10 as well as a summary and interpretation of the modeling framework.Supplemental Results File S3 presents detailed model outputs for typical T2D progression.Supplemental Code File S4 provides the code for the typical T2D progression model and the ABCC8 variant model.