Alterations in Enteroendocrine Hormones After Total Pancreatectomy With Islet Autotransplantation

Abstract

Objective: When total pancreatectomy with islet autotransplantation (TPIAT) is performed for chronic pancreatitis, the pancreas and most of the duodenum are removed, with Roux-en-Y reconstruction of the gastrointestinal tract. Enteroendocrine cells in the intestines and pancreas secrete hormones coordinating digestion and motility, but anatomic reconstruction alters transit of nutrients to these cells. We hypothesized that TPIAT leads to changes in enteroendocrine hormones.

Methods: Glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and pancreatic polypeptide (PP) were measured from mixed-meal tolerance tests of 34 clinical trial participants before and 18 months after TPIAT. Area under the curve of GLP-1 and PYY-stimulated responses were calculated by trapezoidal method, and the PP response was measured as the stimulated max minus baseline (ΔPP).

Results: Area under the curve of GLP-1 and PYY increased significantly after TPIAT (GLP-1 average +553.1 pg/mL per minute, P = 0.004; PYY average +4647.9 pg/mL per minute, P = 0.02). ΔPP trended toward lower after TPIAT (average, -52.2 pg/mL, P = 0.06).

Conclusions: In this novel study of enteroendocrine hormones in TPIAT patients, stimulated levels of GLP-1 and PYY were significantly higher after versus before TPIAT. ΔPP was lower after TPIAT, but not significantly. These hormone changes have potential clinical implications that warrant further research.

FIGURE 1.

Comparison of mean pre-versus post-TPIAT PYY (A), and GLP-1 (B) responses to MMTT. Error bars represent standard error of the mean. AUC, area under the curve measured by trapezoidal method. A P value of <0.05 was considered statistically significant.

FIGURE 2.

Pre-TPIAT GLP-1 levels for participants who had undergone previous intestinal rearrangement (prior surgery), versus those who did not have previous intestinal rearrangement. Average difference in AUC of GLP-1 +861 ± 375 for participants with prior intestinal rearrangement. Patients with four different prior surgical procedures were grouped together for statistical analysis: Whipple (square), distal gastrectomy with Billroth-1 reconstruction (triangle), Roux-en-Y gastric bypass (diamond), and Puestow (star).

FIGURE 3.

Post-TPIAT GLP-1 levels for participants who no longer retained their pylorus versus those whose pylorus remained intact. Average difference in AUC +1702 ± 801 for participants with pylorus absent. P value adjusted for age, sex, and clinical trial treatment assignment.

FIGURE 4.

Comparison of ΔPP response to MMTT pre- versus post-TPIAT. Average change −33.5 ± 17.2 after TPIAT.