Beyond the loss of beta cells: a quantitative analysis of islet architecture in adults with and without type 1 diabetes – published online 26/02/2025

Nicolás Verschueren van Rees, Peter Ashwin, Conor McMullan, Lars Krogvold, Knut Dahl‑Jorgensen, Noel G. Morgan, Pia Leete, Kyle C. A. Wedgwood

Understanding nuance within datasets focused on human type 1 diabetes is key for exploring disease heterogeneity, pathological mechanisms and targets for individualised therapies. In this issue, Verschueren van Rees et al (https://doi.org/10.1007/s00125-025-06376-9) quantitatively assess the existence of a mantle–core structure in islets from healthy individuals and individuals with type 1 diabetes. The authors use an analysis pipeline that incorporates machine learning and statistical analysis with 6-plex staining and spectrally-unmixed, whole-slide immunofluorescent imaging to investigate the architecture of human islets from 2D images. Combining these tools, they confirm the mantle–core structure at both aggregated and individual islet scales across whole sections. The authors emphasise accessibility, providing interpretable, portable methods that are adaptable to other datasets. The authors conclude that this method supports the viability of using rodent models to study islet biology at the molecular level and presents a tool for transplantation studies as well as those exploring complex distribution patterns between healthy and heterogeneous disease phenotypes in single- and multiplex datasets.