# Explainable AI-based analysis of human pancreas sections identifies traits of type 2 diabetes

**Authors:** Lukas Klein, Sebastian Ziegler, Felicia Gerst, Yanni Morgenroth, Karol Gotkowski, Eyke Schöniger, Martin Heni, Nicole Kipke, Daniela Friedland, Annika Seiler, Ellen Geibelt, Hajime Yamazaki, Hans-Ulrich Häring, Silvia Wagner, Silvio Nadalin, Alfred Königsrainer, Andre L. Mihaljevic, Daniel Hartmann, Falko Fend, Daniela Aust, Jürgen Weitz, Reiner Jumpertz-von Schwartzenberg, Marius Distler, Klaus Maier-Hein, Andreas L. Birkenfeld, Susanne Ullrich, Paul F. Jäger, Fabian Isensee, Michele Solimena, Robert Wagner

PMC · DOI: 10.1038/s41467-026-69295-2 · Nature Communications · 2026-02-09

## TL;DR

Researchers used explainable AI to analyze pancreas tissue and found specific tissue changes that distinguish people with type 2 diabetes.

## Contribution

A novel data-driven approach using explainable AI to identify T2D-related tissue traits, including islet-cell interactions and fat cell alterations.

## Key findings

- Larger adipocyte clusters and altered islet-adipocyte proximity are linked to T2D.
- Smaller islets and changes in α- and δ-cells and neuronal axons are predictive of T2D status.
- The AI model achieved high prediction performance by integrating multiple tissue features.

## Abstract

Type 2 diabetes (T2D) is a chronic disease currently affecting around 500 million people worldwide with often severe health consequences. Yet, histopathological analyses are still inadequate to infer the glycaemic state of a person based on morphological alterations linked to impaired insulin secretion and β-cell failure in T2D. Giga-pixel microscopy can capture subtle morphological changes, but data complexity exceeds human analysis capabilities. In response, we generate a dataset of pancreas whole-slide images from living donors with multiple chromogenic and multiplex immunofluorescence stainings and train deep learning models to predict the T2D status. Using explainable AI, we make the learned relationships interpretable, quantify them as biomarkers, and assess their association with T2D. Remarkably, the highest prediction performance is achieved by simultaneously focusing on islet α- and δ-cells and neuronal axons, alongside subtle pancreatic alterations in T2D donors such as larger adipocyte clusters, altered islet-adipocyte proximity and smaller islets. This data-driven approach provides a foundation for future research into relevant diagnostic and therapeutic targets, refining several hypotheses regarding tissue alterations associated with T2D.

Researchers used explainable AI to analyze pancreas tissue from living donors, revealing that changes in fat cell clusters, nerve structures, and islet proximity to fat cells distinguish people with type 2 diabetes from those without the condition.

## Linked entities

- **Diseases:** type 2 diabetes (MONDO:0005148)

## Full-text entities

- **Diseases:** beta-cell failure (MESH:D051437), T2D (MESH:D003924), impaired insulin secretion (MESH:D007333)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12894717/full.md

## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12894717/full.md

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Source: https://tomesphere.com/paper/PMC12894717