Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Clinical research
  • Published:

Blood glucose, glucose balance, and disease-specific survival after prostate cancer diagnosis in the Finnish Randomized Study of Screening for Prostate Cancer

Abstract

Introduction

Diabetes mellitus has been linked with adverse prostate cancer (PCa) outcomes. However, role of hyperglycemia in PCa progression is unclear. We evaluated the link between hyperglycemia and PCa survival among Finnish PCa patients.

Methods

The study cohort included 1770 men with data on fasting glucose and diagnosed with PCa within the Finnish Randomized Study of Screening for PCa in 1995–2009. Additionally, 1398 men had data on glycated hemoglobin (HbA1c). Information on fasting glucose and HbA1c measurements was obtained from the regional laboratory database. Antidiabetic medication use was obtained from the prescription database of the Social Insurance Institution (SII). Time-dependent Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals for PCa death among diabetic, impaired glucose tolerant, and normoglycemic men.

Results

During median follow-up of 9.9 years after the diagnosis, 182 men died from PCa. After adjustment for tumor stage, Gleason grade, and PSA level at diagnosis, diabetic fasting glucose level after PCa diagnosis was associated with elevated risk of PCa death compared to normoglycemic men (HR 1.67 95% CI 1.18–2.36). The risk association was strongest among participants with localized cancer at diagnosis; HR 2.39, 95% CI 1.45–3.93. The risk elevation was observed for glucose measurements taken up to 5 years earlier. Diabetic glucose levels measured before the diagnosis were not associated with PCa death.

Conclusion

Our study cohort suggests an increased risk of PCa death in men with diabetic fasting blood glucose levels, supporting the role of hyperglycemia as a risk factor for PCa progression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Crawley DJ, Holmberg L, Melvin JC, Loda M, Chowdhury S, Rudman SM et al. Serum glucose and risk of cancer: a meta-analysis. BMC Cancer. 2014;14:1.

    Article  Google Scholar 

  2. Shikata K, Kentaro, Ninomiya T, Kiyohara Y. Diabetes mellitus and cancer risk: review of the epidemiological evidence. Cancer Sci. 2013;104.1:9–14.

    Article  Google Scholar 

  3. Barbosa-Desongles A, Hernández C, De Torres I, Munell F, Poupon MF, Simó R et al. Diabetes protects from prostate cancer by downregulating androgen receptor: new insights from LNCaP cells and PAC120 mouse model. PLoS ONE. 2013;8:e74179.

    Article  CAS  Google Scholar 

  4. Pandeya DR, Mittal A, Sathian B, Bhatta B. Role of hyperinsulinemia in increased risk of prostate cancer: a case control study from Kathmandu Valley. Asian Pac J Cancer Prev. 2014;15:1031–3.

    Article  Google Scholar 

  5. Hsing AW, Chua S, Gao YT, Gentzschein E, Chang L, Deng J et al. Prostate cancer risk and serum levels of insulin and leptin: a population-based study. J Natl Cancer Inst. 2001;93.10:783–9.

    Article  Google Scholar 

  6. Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology. 2007;132.6:2208–25.

    Article  Google Scholar 

  7. Kheterpal E, Sammon JD, Diaz M, Bhandari A, Trinh QD, Pokala N et al. Effect of metabolic syndrome on pathologic features of prostate cancer. Urol Oncol. 2013;31:1054–9.

    Article  Google Scholar 

  8. Hsing AW, Sakoda LC, Chua S. Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr. 2007;86.3:843S–57S.

    Article  Google Scholar 

  9. Kilpeläinen TP, Tammela TL, Malila N, Hakama M, Santti H, Määttänen L et al. Prostate cancer mortality in the Finnish randomized screening trial. J Natl Cancer Inst. 2013;105:719–25.

    Article  Google Scholar 

  10. Lee J, Giovannucci E, Jeon JY. Diabetes and mortality in patients with prostate cancer: a meta-analysis. 2016;5.1:1548.

    Google Scholar 

  11. Cai H, Xu Z, Yu B, Zou Q. Diabetes mellitus is associated with elevated risk of mortality amongst patients with prostate cancer: a meta‐analysis of 11 cohort studies. Diabetes Metab Res Rev. 2015;31.4:336–43.

    Article  Google Scholar 

  12. Bensimon L, Yin H, Suissa S, Pollak MN, Azoulay L. Type 2 diabetes and the risk of mortality among patients with prostate cancer. Cancer Causes Control. 2014;25.3:329–38.

    Article  Google Scholar 

  13. Ryu TY, Park J, Scherer PE. Hyperglycaemia as a risk factor for cancer progression. Diabetes Metab J. 2014;38.5:330–6.

    Article  Google Scholar 

  14. Kim HS, Presti JC Jr, Aronson WJ, Terris MK, Kane CJ, Amling CL et al. Glycemic control and prostate cancer progression: results from the SEARCH database. Prostate. 2010;70.14:1540–6.

    Google Scholar 

  15. Gapstur SM1, Gann PH, Colangelo LA, Barron-Simpson R, Kopp P, Dyer A et al. Postload plasma glucose concentration and 27-year prostate cancer mortality (United States). Cancer Causes Control. 2001;12.8:763–72.

    Article  Google Scholar 

  16. Chan JM, Latini DM, Cowan J, Duchane J, Carroll PR. History of diabetes, clinical features of prostate cancer, and prostate cancer recurrence-data from CaPSURE (United States). Cancer Causes Control. 2005;16.7:789–97.

    Article  Google Scholar 

  17. Haring A, Murtola TJ, Talala K, Taari K, Tammela TL, Auvinen A. Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Scand J Urol. 2017;51.1:5–12.

    Article  Google Scholar 

  18. Joentausta RM, Kujala PM, Visakorpi T, Tammela TL, Murtola TJ. Tumor features and survival after radical prostatectomy among antidiabetic drug users. Prostate Cancer Prostatic Dis. 2016;19:367–73.

    Article  CAS  Google Scholar 

  19. Arthur R, Møller H, Garmo H, Holmberg L, Stattin P, Malmstrom H et al. Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories. Cancer Med. 2016;5:1307–18.

    Article  CAS  Google Scholar 

  20. Masur K, Vetter C, Hinz A, Tomas N, Henrich H, Niggemann B et al. Diabetogenic glucose and insulin concentrations modulate transcripton and protein levels involved in tumour cell migration, adhesion and proliferation. Br J Cancer. 2011;104.2:345–52.

    Article  Google Scholar 

  21. Murtola TJ, Wahlfors T, Haring A, Taari K, Stenman UH, Tammela TL et al. Polymorphisms of genes involved in glucose and energy metabolic pathways and prostate cancer: interplay with metformin. Eur Urol. 2015;68.6:1089–97.

    Article  Google Scholar 

  22. Draznin B. Mechanism of the mitogenic influence of hyperinsulinemia. Diabetol Metab Syndr. 2011;3.1:1.

    Google Scholar 

  23. Micucci C, Valli D, Matacchione G, Catalano A. Current perspectives between metabolic syndrome and cancer. Oncotarget. 2016;7:38959–72.

  24. Chan JM, Gann PH, Giovannucci EL. Role of diet in prostate cancer development and progression. J Clin Oncol. 2005;23.32:8152–60.

    Article  Google Scholar 

  25. Huncharek M, Haddock KS, Reid R, Kupelnick B. Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health. 2010;100.4:693–701.

    Article  Google Scholar 

  26. Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM. Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor. Cancer Res. 2011;71.11:3889–95.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Teemu J. Murtola.

Ethics declarations

Conflict of interest

TJM: lecture fees from Astellas, Janssen, and MSD and paid consultant for Astellas and Jansen. KT: lecture fee from GSK, consultant fee from Abbvie, research funding from Medivation, and congress travel support from Astellas and Orion. TLJT: paid consultant for Astellas, GSK, Pfizer, Orion Pharma, and Amgen. AA: lecture fee from MSD and paid consultant for Epid Research. The other authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murtola, T.J., Sälli, S.M., Talala, K. et al. Blood glucose, glucose balance, and disease-specific survival after prostate cancer diagnosis in the Finnish Randomized Study of Screening for Prostate Cancer. Prostate Cancer Prostatic Dis 22, 453–460 (2019). https://doi.org/10.1038/s41391-018-0123-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-018-0123-0

This article is cited by

Search

Quick links