title: Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma.
abstract: OBJECTIVE
  To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis.
  
  
  METHODS
  Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression.
  
  
  RESULTS
  Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 ± 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 ± 9 vs. 66.8 ± 10 years, p = 0.68), but were more likely to have a cancer stage ≥3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 ± 0.14 and 1.79 ± 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival.
  
  
  CONCLUSIONS
  Insulin resistance is associated with the aggressiveness of PDAC.
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Dugnani
authors.affiliation: Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Balzano
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pasquale
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Scavini
authors.affiliation: Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aleotti
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Liberati
authors.affiliation: Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Di Terlizzi
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gandolfi
authors.affiliation: Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Petrella
authors.affiliation: Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.affiliation: Department of Pathology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bosi
authors.affiliation: Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. piemonti.lorenzo@hsr.it.
authors.forename: Lorenzo
authors.identifier: http://orcid.org/0000-0002-2172-2198
authors.initials: L
authors.lastname: Piemonti
mesh_terms: D000367:Age Factors; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D007328:Insulin
keywords: Human; Insulin resistance; Pancreatic ductal carcinoma