Type 1 Diabetes and the Exocrine Pancreas

Type 1 diabetes (T1D) has long been understood as a disease of the pancreatic islets, where immune-mediated destruction of insulin-producing beta cells drives hyperglycemia. My PhD work challenged this tissue-centric view by integrating T1D genome-wide association study (GWAS) loci with single-cell chromatin accessibility maps of the human pancreas, revealing that a substantial proportion of T1D risk variants are active in acinar cells, the exocrine compartment responsible for digestive enzyme secretion. This finding, published in (Chiou et al., 2021), implicated acinar dysfunction as a previously underappreciated component of T1D pathophysiology.

Building on this, subsequent work from our lab showed that circulating pancreatic enzyme levels are a causal biomarker of T1D risk (Elgamal et al., 2024), and single-cell multiome profiling of pancreas tissue across disease stages revealed dynamic cell-type-specific regulatory programs during T1D progression (Melton et al., 2025). Together, these studies shifted the field’s view of T1D from a purely islet-centric disease to one with measurable exocrine contributions, opening new avenues for early detection and intervention.

Data and code: joshchiou/T1D_snATAC

Related: Single-Cell Epigenomics of Pancreatic Islets — companion project mapping islet cell-type chromatin accessibility and type 2 diabetes risk variants.