SAT-514 - Chronic Pancreatitis and Acinar Atrophy by Histopathology Characterize Young Npod Donors with Reduced Pancreas Organ Weight and May Precede This Finding in the Progression to Type 1 Diabetes

Previous studies have reported reduced relative pancreas weight (RPW; PW [g] / body weight [kg]) in individuals with type 1 diabetes (T1D) and in islet autoantibody-positive (AAb+) organ donors, along with higher incidences of acute and chronic pancreatitis in T1D donors. The relationship between pancreatic size and exocrine pathology, however, remains unclear. We investigated the prevalence of exocrine pancreatic abnormalities, including chronic pancreatitis, acute pancreatitis, acinar atrophy, fatty infiltration, and interstitial fibrosis, across T1D, single AAb+, multiple AAb+, and control donors, and examined their association with RPW. We hypothesized that exocrine changes would be more pronounced in multiple AAb+ and T1D donors but not in single AAb+ donors, and that these changes would correlate with lower RPW.

All nPOD donors with T1D (n=116), single AAb+ (n=17), multiple AAb+ (n=7), and controls (n=139) available through June 2022, aged ≤25 years at the time of death, were included. Donor demographics and RPW were obtained from the nPOD DataShare portal, and histopathologic images were reviewed via the nPOD online pathology database. We evaluated insulin positivity, insulitis, and acute (acinar cell loss, polymorphonuclear infiltrate, fat necrosis, hemorrhage) and chronic (acinar cell loss, mononuclear infiltrate, fibrosis) pancreatitis, as well as acinar atrophy, fatty infiltration, and interstitial fibrosis.

Subjects exhibiting chronic pancreatitis (p=0.016) or acinar atrophy (p < 0.0001) had significantly lower RPW both overall and within T1D donors (p=0.0012 and p=0.04, respectively). No significant differences in RPW or exocrine histopathology were observed in single AAb+ donors. Multiple AAb+ donors demonstrated increased prevalence of chronic pancreatitis (p=0.01) and acinar atrophy (p=0.03), without corresponding differences in RPW. T1D donors were more likely to exhibit acute pancreatitis (p=0.0005), chronic pancreatitis (p < 0.0001), acinar atrophy (p < 0.0001), and reduced RPW (p < 0.001), with longer disease duration associated with smaller RPW (r=-0.43, p< 0.0001).

In this young cohort, reduced RPW was strongly associated with acinar atrophy and chronic pancreatitis, both overall and among T1D donors, suggesting that decreased pancreatic size may serve as a marker of exocrine pathology. Notably, acinar changes were detectable in multiple AAb+ donors even in the absence of RPW reduction, indicating that inflammatory alterations may precede measurable loss of pancreatic volume.

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