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Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma

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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.

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Abbreviations

DM:

Diabetes mellitus

FPG:

Fasting plasma glucose

GNRI:

Geriatric Nutritional Risk Index

IR:

Insulin receptor

IQR:

Interquartile range

LMR:

Lymphocyte-to-monocyte ratio

NLR:

Neutrophil-to-lymphocyte ratio

PDAC:

Pancreatic ductal adenocarcinoma

PLR:

Platelet-to-lymphocyte ratio

PNI:

Onodera’s prognostic nutrition index

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Acknowledgments

Funding

This study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC, bando 5 x 1,000 N_12182 and Progetto IGN_ 11783).

Author contributions

G.B., F.A., G.D.T. and G.P. enrolled and managed the patients. A.G., E.D., V.P., D.L., C.D. and M.R. researched data and managed the patients during follow-up. M.S., E.B. and M.F. reviewed/edited manuscript and contributed to the discussion. LP developed the concept, designed the study, wrote the manuscript, promoted the study and researched data. The name of the guarantor for this study is Lorenzo Piemonti.

Author information

Author notes

    Authors and Affiliations

    1. Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy

      Erica Dugnani, Valentina Pasquale, Marina Scavini, Daniela Liberati, Alessandra Gandolfi, Emanuele Bosi & Lorenzo Piemonti

    2. Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy

      Gianpaolo Balzano, Francesca Aleotti & Massimo Falconi

    3. Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy

      Gaetano Di Terlizzi, Giovanna Petrella & Michele Reni

    4. Department of Pathology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy

      Claudio Doglioni

    5. Vita-Salute San Raffaele University, Milan, Italy

      Claudio Doglioni & Massimo Falconi

    Authors
    1. Erica Dugnani
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    2. Gianpaolo Balzano
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    14. Lorenzo Piemonti
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    Corresponding author

    Correspondence to Lorenzo Piemonti.

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    Conflict of interest

    All the authors declare that have no conflict of interest to disclose.

    Ethical standard

    This study has been performed in accordance with the ethical standards of San Raffaele Scientific Institute Ethics Committee and with the Helsinki Declaration and its later amendments.

    Human and animal rights

    All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

    Informed consent

    Informed consent was obtained from all patients prior to be included in the study.

    Additional information

    Managed by Antonio Secchi.

    Erica Dugnani and Gianpaolo Balzano equally contributed to this manuscript.

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    Cite this article

    Dugnani, E., Balzano, G., Pasquale, V. et al. Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma. Acta Diabetol 53, 945–956 (2016). https://doi.org/10.1007/s00592-016-0893-6

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    • DOI: https://doi.org/10.1007/s00592-016-0893-6

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