A reduced pancreatic polypeptide response is associated with new onset pancreatogenic diabetes versus type 2 diabetes.

PURPOSE: Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM).

METHODS: Subjects with new onset DM (<3 years duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test (MMTT), then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of PP concentrations between groups were performed using Wilcoxon rank-sum test and analysis of covariance (ANCOVA) while adjusting for age, sex, and BMI.

RESULTS: The fasting PP concentration was lower in both PDAC-DM and CP-DM groups than the T2DM group (p = 0.03 and <0.01, respectively). The fold change in PP at 15 minutes following meal stimulation was significantly lower in the PDAC-DM (median 1.869) and CP-DM (1.813) groups compared to T2DM (3.283, p < 0.01 for both comparisons). The area under the curve (AUC) of PP concentration was significantly lower in both PDAC-DM and CP-DM groups than T2DM regardless of the interval used for calculation, and remained significant after adjustments.

CONCLUSIONS: Fasting PP concentrations and the response to meal stimulation are reduced in new onset DM associated with PDAC or CP compared to T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM, and to understand the pathophysiological role in exocrine pancreatic diseases. (NCT03460769).