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 (INS-PND) have a marked reduction in pancreas volume by MRI compared with 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, including maturity-onset diabetes of the young (MODY) and PND (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 control participants with ND (n = 90). Across all monogenic diabetes groups, individuals receiving insulin therapy had significantly smaller pancreas volume compared with those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes.

Individuals with type 1 diabetes (T1D) have a markedly smaller pancreas, but the mechanism responsible for the reduction in size is unknown. How pancreas volume differs in individuals with specific forms of monogenic diabetes and how pancreas volume relates to the severity of insulin deficiency are unknown. Measured by MRI, individuals with permanent neonatal diabetes due to an INS gene mutation (INS-PND) or the HNF1B gene associated with maturity-onset diabetes of the young had smaller pancreas than individuals without diabetes. Across all types of monogenic diabetes, individuals receiving insulin replacement therapy had smaller pancreas than individuals not using insulin. These results support the conclusion that insulin deficiency is a major factor contributing to changes in pancreas volume in T1D, INS-PND, and other forms of monogenic diabetes.