Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma

Acta Diabetol. 2016 Dec;53(6):945-956. doi: 10.1007/s00592-016-0893-6. Epub 2016 Aug 23.

Abstract

Aims: 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.

Keywords: Human; Insulin resistance; Pancreatic ductal carcinoma.

Publication types

  • Observational Study

MeSH terms

  • Age Factors
  • Aged
  • Carcinoma, Pancreatic Ductal* / epidemiology
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Disease Progression
  • Female
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Pancreatic Neoplasms* / epidemiology
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Prospective Studies
  • Survival Analysis

Substances

  • Insulin