Lower plasma levels of glucose-dependent insulinotropic peptide (GIP) and pancreatic polypeptide (PP) in patients with ductal adenocarcinoma of the pancreas and their relation to the presence of impaired glucoregulation and weight loss

Pancreatology. Jan-Feb 2017;17(1):89-94. doi: 10.1016/j.pan.2016.12.004. Epub 2016 Dec 15.

Abstract

Background: The changes in gastrointestinal hormones associated with pancreatic ductal adenocarcinoma (PDAC) in patients with impaired glucoregulation have yet to be evaluated. The aim of this study was to determine plasma concentrations of selected gastrointestinal hormones in PDAC patients with and without diabetes and to compare them with levels found in Type 2 diabetic patients without cancer.

Methods: In this study we examined plasma concentrations of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1), pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY), and cytokines leptin and adiponectin in 94 patients with histologically confirmed PDAC. Thirty-nine patients with Type 2 diabetes without PDAC and 29 healthy individuals with no evidence of acute or chronic diseases were examined as controls.

Results: Significantly lower plasma concentrations of GIP were found in PDAC patients with new-onset diabetes/prediabetes (n = 76), or in those with normal glucose regulation (n = 18), compared to patients with Type 2 diabetes without PDAC and controls (15.5 (3.7-64.5) or 6.5 (1.7-24.5) vs. 39.8 (15.1-104.7) and 28.8 (7.4-112.2) ng/L, p < 0.001); the same relationship was observed for PP (38.9 (10.2-147.9) or 28.1 (7.9-100.0) vs 89.1 (38.0-208.9) and 75.8 (30.1-190.6) ng/L, p < 0.01), respectively. The lowest levels of GIP and PP concentrations were found in PDAC patients with new-onset diabetes/prediabetes and weight loss > 2 kg (p < 0.001).

Conclusions: We conclude that GIP and PP plasma concentrations are lower in pancreatic cancer irrespective of the degree of glucose intolerance as compared to Type 2 diabetic patients and healthy controls. In new onset diabetes especially if associated with weight loss, these changes may represent a new clue for the diagnosis of PDAC.

Keywords: Diabetes mellitus; Glucose-dependent insulinotropic peptide; Pancreatic ductal adenocarcinoma; Pancreatic polypeptide.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / complications
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / physiopathology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Gastric Inhibitory Polypeptide / blood*
  • Glucagon-Like Peptide 1 / blood
  • Glucose Intolerance / blood
  • Glucose Intolerance / complications
  • Glucose Intolerance / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Neuropeptide Y / blood
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / physiopathology
  • Pancreatic Polypeptide / blood*
  • Peptide YY / blood
  • Weight Loss*

Substances

  • Biomarkers
  • Blood Glucose
  • Neuropeptide Y
  • Peptide YY
  • Gastric Inhibitory Polypeptide
  • Pancreatic Polypeptide
  • Glucagon-Like Peptide 1