FIG. 1.

Relationship between insulin release in relation to the remaining β-cell mass. Research subjects entering an intervention trial at 8–35 years of age at the time of clinical diagnosis, such as the Protégé trial, may have vastly different baselines that may affect treatment and outcome. Subjects to the left may have lost a major proportion of their β-cells but still remain asymptomatic due to well-functioning β-cells and high insulin sensitivity. Subjects to the right may develop diabetes due to poor β-cell function and high insulin resistance. Heterogeneity already at baseline complicates immunomodulation intervention trials in T1D. The figure is courtesy of Daniel Cook and Ian Sweet, University of Washington, Seattle, Washington.