Quantitative analysis of human adult pancreatic histology reveals separate fatty and fibrotic phenotypes in type 2 diabetes – Published online 24/09/2025

Nicola J. Dyson, Nicole Kattner, Yara Al‑Selwi, Minna Honkanen‑Scott, Morgan F. Shaw, Caitlin A. Brack, Rowen Coulthard, Christine S. Flaxman, Sarah J. Richardson, James A. M. Shaw

Increasing pancreatic fat content with increasing BMI has been consistently reported, but whether a further increase is pathognomonic of progression to type 2 diabetes remains unclear. In this issue, Dyson et al (https://doi.org/10.1007/s00125-025-06547-8) report the findings of a systematic study of the role of intra-pancreatic lipid and collagen in type 2 diabetes pathogenesis using whole pancreases obtained from deceased organ donors with and without type 2 diabetes. The authors found a higher adipocyte proportional area in donors with type 2 diabetes compared with donors with a comparable BMI but without diabetes. Adipocyte proportional area was inversely associated with acinar lipid droplet content and endocrine lipid content was not significantly higher in type 2 diabetes. A subgroup of donors with clinical type 2 diabetes had a relatively low adipocyte content but extensive collagen deposition without pathological changes associated with pancreatitis. The authors conclude that these data suggest that the association between pancreatic fat and diabetes may be driven by adipocytes as opposed to intracellular lipid signalling and that there is a separate subgroup characterised by pancreatic fibrosis without excess visceral fat.

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