title: 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.
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.
authors.affiliation: 3rd Department of Internal Medicine and Laboratory for Endocrinology and Metabolism, Prague, Czechia. Electronic address: jan.skrha@lf1.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Škrha
authors.affiliation: Department of Biochemistry and Experimental Oncology, Prague, Czechia.
authors.forename: Petr
authors.initials: P
authors.lastname: Bušek
authors.affiliation: Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czechia.
authors.forename: Jana
authors.initials: J
authors.lastname: Uhrová
authors.affiliation: Department of Pathology, University Military Hospital of the Czech Ministry of Health and 1st Faculty of Medicine, Charles University, Prague, Czechia.
authors.forename: Petr
authors.initials: P
authors.lastname: Hrabal
authors.affiliation: Department of Internal Medicine, University Military Hospital of the Czech Ministry of Health and 1st Faculty of Medicine, Charles University, Prague, Czechia.
authors.forename: Klára
authors.initials: K
authors.lastname: Kmochová
authors.affiliation: Department of Internal Medicine, University Military Hospital of the Czech Ministry of Health and 1st Faculty of Medicine, Charles University, Prague, Czechia.
authors.forename: Martin
authors.initials: M
authors.lastname: Laclav
authors.affiliation: Department of Internal Medicine, University Military Hospital of the Czech Ministry of Health and 1st Faculty of Medicine, Charles University, Prague, Czechia.
authors.forename: Bohuš
authors.initials: B
authors.lastname: Bunganič
authors.affiliation: Department of Internal Medicine, University Military Hospital of the Czech Ministry of Health and 1st Faculty of Medicine, Charles University, Prague, Czechia.
authors.forename: Přemysl
authors.initials: P
authors.lastname: Frič
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000097:blood; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D010191:Pancreatic Polypeptide / Q000097:blood*; D019894:Peptide YY / Q000097:blood; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D009478:Neuropeptide Y; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D052216:Glucagon-Like Peptide 1
keywords: Diabetes mellitus; Glucose-dependent insulinotropic peptide; Pancreatic ductal adenocarcinoma; Pancreatic polypeptide