Smaller pancreas volume in insulin-dependent monogenic diabetes

Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an INS gene mutation have a marked reduction in pancreas volume by MRI compared to control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss of pancreas volume in diabetes, we used a standardized and validated MRI protocol to measure pancreas volumes in individuals with various forms of monogenic diabetes (HNF4A-MODY, GCK-MODY, HNF1A-MODY, HNF1B-MODY, INS-MODY, or INS-PND, n = 37), and compared their pancreas volumes with those of previously reported individuals with T1D (n = 93) or healthy ND controls (n = 90). Across all monogenic diabetes groups, individuals on insulin therapy had significantly smaller pancreas volume compared to those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes.