3D imaging of an entire pancreas shows inverse proportions of extra-islet versus islet-associated β cells in late-onset type 1 diabetes.

Residual β cell function can positively affect diabetes regulation in type 1 diabetes (T1D), but details on residual β cell mass distribution in T1D is largely lacking in a whole organ context. Implementing an optical 3D imaging pipeline, we generated a complete account of the remaining β cells throughout an entire human late onset T1D pancreas at a microscopic resolution. Our data show that most of the residual β cells were present as scattered individual cells or as punctated clusters of individual β cells, spatially separated from each other and all other endocrine cell types. Compared to islet-associated β cells, extra-islet β cells appeared in a substantially higher relative abundance in the head region of the T1D pancreas. This 3D depiction of an entire T1D pancreas shows that individual β cells may be preserved and/or formed in a highly regionalized manner, potentially reflecting key aspects of disease dynamics, advocating for increased focus on extra-islet islet β cells in attempts to develop strategies for pancreatic β cell preservation in T1D.