Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories toward type 2 diabetes

To gain insight into the history of islet cell deterioration along the progression from normal glycemic regulation to T2D, we collected surgical pancreatic tissue samples from 133 metabolically phenotyped pancreatectomized patients (PPP). Gene expression profiles of islets isolated by laser capture microdissection (LCM) from resected and snap-frozen pancreas samples were assessed by RNA sequencing. Overall design: This study includes RNA-Seq samples from pancreatic islets of 133 human donors, stratified into four groups based on their diabetes status: 18 were non-diabetic (ND), 41 had impaired glucose tolerance (IGT), 35 had Type 3c diabetes (T3cD), and 39 had Type 2 diabetes (T2D). The group assignments are based on thresholds defined in the guidelines of the American Diabetes Association. For data analysis, a subset of 92 pancreatic islet samples was defined, which included only those samples in which the gene INS showed the highest expression (i.e., highest normalized counts value). Statistical analyses were performed both on the complete transcriptomics data set and on this restricted data set.