Natural history of insulin secretion and glucose tolerance during progression from early stages of T1D through stage 3 and beyond

Stylized depiction of stimulated insulin secretion (area under the curve C-peptide during an oral glucose tolerance test) as individuals progress from early stages of T1D through clinical diagnosis and subsequently. When multiple AABs are detected, insulin secretion is already low compared with reference (red dotted line) and glucose tolerance remains normal (stage 1 T1D, blue box). Insulin secretion gradually increases before diagnosis, likely as a compensatory response for worsening glucose tolerance (stage 2 T1D, orange box), and then falls 6 to 12 months before clinical diagnosis. The rate of decline in insulin secretion does not change through clinical diagnosis. Post-diagnosis, residual secretion at low levels is frequently detectable.