To discuss advances in our understanding of beta-cell heterogeneity and the ramifications of this for type 1 diabetes (T1D) and its therapy.

A number of studies have challenged the long-standing dogma that the majority of beta cells are eliminated in T1D. As many as 80% are present in some T1D subjects. Why don’t these cells function properly to release insulin in response to high glucose? Other findings deploying single-cell “omics” to study both healthy and diseased cells—from patients with both T1D and type 2 diabetes (T2D)—have revealed cell subpopulations and heterogeneity at the transcriptomic/protein level between individual cells. Finally, our own and others’ findings have demonstrated the importance of functional beta-cell subpopulations for insulin secretion.

Heterogeneity may endow beta cells with molecular features that predispose them to failure/death during T1D.