Pancreatic polypeptide response to a mixed meal is blunted in pancreatic head cancer associated with diabetes mellitus

Introduction Pancreatic polypeptide (PP) is a hormone secreted by islet cells of the ventral pancreas. It has been proposed that a blunted PP response to a mixed meal can distinguish diabetes mellitus (DM) secondary to pancreatic disease from other types of DM. We performed a proof of concept study to determine if PP response to a mixed meal discriminates DM secondary to pancreatic cancer (PaCDM) from type 2 DM (T2DM). Methods We studied 18 subjects with new onset DM (PaCDM (n = 9) and T2DM (n = 9); matched for age and gender). Serum PP levels were measured at 0, 30, and 60 min following a mixed meal. Increases in PP levels from baseline were compared using the Wilcoxon test. Results In PaCDM the PP increase following a mixed meal was less than T2DM at 30 min (median 60.0%, IQR, 33.0-119.8 vs. 134.5%, IQR, 117.5-265.9; p = 0.03), but statistically similar at 60 min (median 55.8%, interquartile range (IQR) 23.7-121.5 vs. 100.0%, IQR, 47.7-202.5; p = 0.17). In PaCDM subjects, the PP increase over baseline was smaller in those with a tumor located in the pancreatic head (n = 6) compared to the body/tail (n = 3) at 30 min (41.3% vs. 158.7%, p = 0.02) and at 60 min (37.4% vs. 167.4%,p = 0.04). Conclusions Subjects with PaCDM have a blunted PP response to a mixed meal compared to T2DM. However, the blunted PP response is only observed in those PaC subjects with a tumor located in the head of the pancreas. Confirmation in larger studies may suggest this could be used to aid screening for sporadic PaC.