Before the Threshold: Hyperinsulinemia as a Candidate Modifiable Driver of β-Cell Exhaustion in Genetically Burdened, Normoglycemic Offspring of Patients With Type 2 Diabetes — A Translational Hypothesis and Prototype Risk Matrix for Trial Design
Background. Type 2 diabetes mellitus (T2DM) is diagnosed at decompensation thresholds — fasting plasma glucose (FPG) ≥126 mg/dL or HbA1c ≥6.5% — that typically declare disease only after substantial β-cell loss. Normoglycemic offspring of parents with T2DM carry several-fold lifetime risk yet receive no structured surv...