title: GDF-15 Is Associated with Cancer Incidence in Patients with Type 2 Diabetes.
abstract: BACKGROUND
  Diabetes has been linked epidemiologically to increased cancer incidence and mortality. Growth differentiation factor 15 (GDF-15) is increased in patients with diabetes and has recently been linked to the occurrence of cancer. We investigated whether circulating GDF-15 concentrations can predict the incidence of malignant diseases in a diabetic patient cohort already facing increased risk for cancer.
  
  
  METHODS
  We prospectively enrolled a total of 919 patients with type 2 diabetes and no history of malignant disease, who were clinically followed up for 60 months. GDF-15, N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline; an additional 4 cardiovascular biomarkers were determined for a subpopulation (n = 259). Study end point was defined as the first diagnosis of any type of cancer during the follow-up period.
  
  
  RESULTS
  During a median follow-up of 60 months, 66 patients (7.2%) were diagnosed with cancer. Baseline circulating GDF-15 concentrations were higher in patients that developed cancer over the follow-up period when compared to cancer-free patients. Increased GDF-15 concentrations were significantly associated with cancer incidence [crude hazard ratio (HR) per 1-IQR (interquartile range) increase 2.13, 95% CI 1.53-2.97, P < 0.001]. This effect persisted after multivariate adjustment with an adjusted HR of 1.86 (95% CI 1.22-2.84; P = 0.004). Among the 4 additionally tested cardiovascular markers in the subpopulation, only troponin T and C-terminal proendothelin-1 showed a significant association with future cancer incidence with unadjusted HRs of 1.71 (95% CI 1.28-2.28, P < 0.001) and 1.68 (95% CI 1.02-2.76, P = 0.042), respectively.
  
  
  CONCLUSIONS
  Increased circulating concentrations of GDF-15 are associated with increased cancer incidence in patients with type 2 diabetes.
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Noemi
authors.initials: N
authors.lastname: Pavo
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Raphael
authors.initials: R
authors.lastname: Wurm
authors.affiliation: Department of Anesthesia, Division of Cardio-Thoracic-Vascular Anesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Neuhold
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.affiliation: Department of Internal Medicine III, Division of Endocrinology, Medical University of Vienna, Vienna, Austria.
authors.forename: Greisa
authors.initials: G
authors.lastname: Vila
authors.affiliation: Technical University Dortmund, Dortmund, Germany; FH Campus Vienna, Vienna, Austria and Complexity Research, Vienna, Austria.
authors.forename: Guido
authors.initials: G
authors.lastname: Strunk
authors.affiliation: Department of Internal Medicine, Hospital Barmherzige Brüder Linz, Linz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Clodi
authors.affiliation: Department of Internal Medicine, Hospital Barmherzige Brüder Linz, Linz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Resl
authors.affiliation: Health Center South, Diabetes Outpatient Clinic, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Brath
authors.affiliation: Department of Medicine III, Hospital Hietzing, Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Prager
authors.affiliation: Department of Internal Medicine III, Division of Endocrinology, Medical University of Vienna, Vienna, Austria.
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; martin.huelsmann@meduniwien.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Hülsmann
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications*; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications* / Q000175:diagnosis
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15