Islet Autotransplant Recipients Have Elevated Proinsulin-to–C-Peptide Ratios Supporting Metabolic Stress as a Cause of Islet Attrition

ARTICLE HIGHLIGHTS: β-cell stress after total pancreatectomy with islet autotransplantation has been proposed an important cause of islet loss. We measured circulating proinsulin-to-C-peptide ratios, measured to determine whether total pancreatectomy with islet autotransplantation recipients exhibit β-cell stress, and whether this is associated with hyperglycemia and other clinical factors. Proinsulin-to-C-peptide ratio levels were elevated twofold or more compared with healthy control volunteers, and were higher with hyperglycemia, high BMI, and low islet mass. These results support the hypothesis that metabolic stress is a cause of long-term islet attrition, and suggests potential opportunity to reduce β-cell stress through maintaining healthy body weight and avoiding significant time in hyperglycemia.