Decreased α-cell mass and early structural alterations of the exocrine pancreas in patients with type 1 diabetes: An analysis based on the nPOD repository

Background and aims Abnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D), but their respective anatomical substrata have seldom been investigated. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of alpha-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD). Materials and methods The ratio of beta- and alpha-cell area to total tissue area were quantified in 75 patients with T1D (thereafter patients) and 66 control subjects (thereafter controls), on 2 insulin-stained and 4 glucagon-stained slides from both the head and the tail of the pancreas. The beta- and alpha-cell masses were calculated in the 66 patients and the 50 controls for which the pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non-acinar, non-insular tissue) to total tissue area ratio was evaluated on both insulin-and glucagon-stained slides. Results were expressed as mean +/- SD. Results An automated quantification method was set up using the R software and was validated by quantification of beta-cell mass, a well characterized parameter. beta-cell mass was 29.6 +/- 112 mg in patients and 628 +/- 717 mg in controls (p<0.0001). alpha-cell mass was 181 +/- 176 mg in patients and 349 +/- 241mg in controls (p<0.0001). Non-exocrine-non-endocrine area to total tissue area ratio was 39 +/- 9% in patients and 29 +/- 10% in controls (p<0.0001) and increased with age in both groups, with no correlation with diabetes duration in patients. Conclusion The absolute alpha-cell mass was lower in patients compared to controls, in proportion to the decrease in pancreas weight observed in patients. Non-exocrine-non-endocrine area to total tissue area ratio increased with age in both groups but was higher in patients at all ages.