Digestive Diseases and Sciences

, Volume 55, Issue 7, pp 1839–1851 | Cite as

Colorectal Cancer Outcomes, Recurrence, and Complications in Persons With and Without Diabetes Mellitus: A Systematic Review and Meta-Analysis

  • Kelly B. Stein
  • Claire F. Snyder
  • Bethany B. Barone
  • Hsin-Chieh Yeh
  • Kimberly S. Peairs
  • Rachel L. Derr
  • Antonio C. Wolff
  • Frederick L. BrancatiEmail author



Diabetes mellitus increases the risk of incident colorectal cancer, but it is less clear if pre-existing diabetes mellitus influences mortality outcomes, recurrence risk, and/or treatment-related complications in persons with colorectal cancer.


We performed a systematic review and meta-analysis comparing colorectal cancer mortality outcomes, cancer recurrence, and treatment-related complications in persons with and without diabetes mellitus. We searched MEDLINE and EMBASE through October 1, 2008, including hand-searching references of qualifying articles. We included studies in English that evaluated diabetes mellitus and cancer treatment outcomes, prognosis, and/or mortality. The initial search identified 8,208 titles, of which 15 articles met inclusion criteria. Each article was abstracted by one author using a standardized form and re-reviewed by another author for accuracy. Authors graded quality based on pre-determined criteria.


We found significantly increased short-term perioperative mortality in persons with diabetes mellitus. In the meta-analysis of long-term mortality, persons with diabetes mellitus had a 32% increase in all-cause mortality compared to those without diabetes mellitus (95% CI: 1.24, 1.41). Although data on other outcomes are limited, available studies suggest that pre-existing diabetes mellitus predicts increased risk of some post-operative complications as well as 5-year cancer recurrence. In contrast, there is little evidence that diabetes confers increased risk for long-term cancer-specific mortality.


Patients with colorectal cancer and pre-existing diabetes mellitus have an increased risk of short- and long-term mortality. Future research should determine whether improvements in prevention and treatment of diabetes mellitus will improve outcomes for colorectal cancer patients.


Colorectal carcinoma Diabetes mellitus Mortality Treatment outcome Fatal outcome 



Frederick L. Brancati: NIDDK Grant (K24DK062222-06); Hsin Chieh Yeh and Frederick Brancati: NIDDK Diabetes Research and Training Center (P60 DK079637); Kelly B. Stein: NIH T32 Training Grant (T32HP10025-14); Bethany B. Barone: NIH T32 Training Grant (T32 DK062707). There were no financial disclosures or conflicts of interest among the authors.


  1. 1.
    US Cancer Statistics Working Group. United States Cancer Statistics: 1999–2004 Incidence and Mortality Web-based Report. Bethesda: Prevention and National Cancer Institute; 2007.Google Scholar
  2. 2.
    Surveillance, Epidemiology, and End Results (SEER). Program Populations (1973–2005). USA: National Cancer Institute; 2008.Google Scholar
  3. 3.
    Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst. 2005;97(22):1679–1687.CrossRefPubMedGoogle Scholar
  4. 4.
    Hu FB, Manson JE, Liu S, et al. Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst. 1999;91(6):542–547. doi: 10.1093/jnci/91.6.542.CrossRefPubMedGoogle Scholar
  5. 5.
    Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol. 2004;159(12):1160–1167. doi: 10.1093/aje/kwh161.CrossRefPubMedGoogle Scholar
  6. 6.
    von Elm E, Altman DG, Egger M, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344–349. doi: 10.1016/j.jclinepi.2007.11.008.CrossRefGoogle Scholar
  7. 7.
    Janssen-Heijnen MLG, Maas HAAM, Houterman S, Lemmens VEPP, Rutten HJT, Coebergh JWW. Comorbidity in older surgical cancer patients: influence on patient care and outcome. Eur J Cancer. 2007;43(15):2179–2193. doi: 10.1016/j.ejca.2007.06.008.CrossRefPubMedGoogle Scholar
  8. 8.
    Lemmens VE, Janssen-Heijnen ML, Verheij CD, Houterman S, Repelaer van Driel OJ, Coebergh JW. Co-morbidity leads to altered treatment and worse survival of elderly patients with colorectal cancer. Br J Surg. 2005;92(5):615–623. doi: 10.1002/bjs.4913.CrossRefPubMedGoogle Scholar
  9. 9.
    Gross CP, McAvay GJ, Guo Z, Tinetti ME. The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer. Cancer. 2007;109(12):2410–2419. doi: 10.1002/cncr.22726.CrossRefPubMedGoogle Scholar
  10. 10.
    Koperna T, Kisser M, Schulz F. Emergency surgery for colon cancer in the aged. Arch Surg. 1997;132(9):1032–1037.PubMedGoogle Scholar
  11. 11.
    Tsugawa K, Koyanagi N, Hashizume M, et al. Therapeutic strategy of emergency surgery for colon cancer in 71 patients over 70 years of age in Japan. Hepatogastroenterology. 2002;49(44):393–398.PubMedGoogle Scholar
  12. 12.
    Little SA, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y. Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer. J Gastrointest Surg. 2002;6(1):88–94. doi: 10.1016/S1091-255X(01)00019-1.CrossRefPubMedGoogle Scholar
  13. 13.
    Davila JA, Rabeneck L, Berger DH, El-Serag HB. Postoperative 30-day mortality following surgical resection for colorectal cancer in veterans: changes in the right direction. Dig Dis Sci. 2005;50(9):1722–1728. doi: 10.1007/s10620-005-2925-x.CrossRefPubMedGoogle Scholar
  14. 14.
    Gross CP, Guo Z, McAvay GJ, Allore HG, Young M, Tinetti ME. Multimorbidity and survival in older persons with colorectal cancer. J Am Geriatr Soc. 2006;54(12):1898–1904. doi: 10.1111/j.1532-5415.2006.00973.x.CrossRefPubMedGoogle Scholar
  15. 15.
    Park SM, Lim MK, Shin SA, Yun YH. Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: national health insurance corporation study. J Clin Oncol. 2006;24(31):5017–5024. doi: 10.1200/JCO.2006.07.0243.CrossRefPubMedGoogle Scholar
  16. 16.
    van de Poll-Franse LV, Houterman S, Janssen-Heijnen ML, Dercksen MW, Coebergh JW, Haak HR. Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int J Cancer. 2007;120(9):1986–1992. doi: 10.1002/ijc.22532.CrossRefPubMedGoogle Scholar
  17. 17.
    Polednak AP. Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study. Cancer Detect Prev. 2006;30(5):466–472. doi: 10.1016/j.cdp.2006.07.003.CrossRefPubMedGoogle Scholar
  18. 18.
    Shonka NA, Anderson JR, Panwalkar AW, Reed EC, Steen PD, Ganti AK. Effect of diabetes mellitus on the epidemiology and outcomes of colon cancer. Med Oncol. 2006;23(4):515–519. doi: 10.1385/MO:23:4:515.CrossRefPubMedGoogle Scholar
  19. 19.
    Meyerhardt JA, Catalano PJ, Haller DG, et al. Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol. 2003;21(3):433–440. doi: 10.1200/JCO.2003.07.125.CrossRefPubMedGoogle Scholar
  20. 20.
    Siddiqui AA, Spechler SJ, Huerta S, Dredar S, Little BB, Cryer B. Elevated HbA1c is an independent predictor of aggressive clinical behavior in patients with colorectal cancer: a case-control study. Dig Dis Sci. 2008;53(9):2486–2494. doi: 10.1007/s10620-008-0264-4.CrossRefPubMedGoogle Scholar
  21. 21.
    Will JC, Galuska DA, Vinicor F, Calle EE. Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol. 1998;147(9):816–825.PubMedGoogle Scholar
  22. 22.
    Payne JE, Meyer HJ. The influence of other diseases upon the outcome of colorectal cancer patients. Aust N Z J Surg. 1995;65(6):398–402. doi: 10.1111/j.1445-2197.1995.tb01767.x.CrossRefPubMedGoogle Scholar
  23. 23.
    Caudle AS, Kim HJ, Tepper JE, et al. Diabetes mellitus affects response to neoadjuvant chemoradiotherapy in the management of rectal cancer. Ann Surg Oncol. 2008;15(7):1931–1936. doi: 10.1245/s10434-008-9873-6.CrossRefPubMedGoogle Scholar
  24. 24.
    Umpleby HC, Bristol JB, Rainey JB, Williamson RC. Survival of 727 patients with single carcinomas of the large bowel. Dis Colon Rectum. 1984;27(12):803–810. doi: 10.1007/BF02553944.CrossRefPubMedGoogle Scholar
  25. 25.
    Arnaud JP, Schloegel M, Ollier JC, Adloff M. Colorectal cancer in patients over 80 years of age. Dis Colon Rectum. 1991;34(10):896–898. doi: 10.1007/BF02049704.CrossRefPubMedGoogle Scholar
  26. 26.
    Begg CB, Schrag D. Attribution of deaths following cancer treatment. J Natl Cancer Inst. 2002;94(14):1044–1045.PubMedGoogle Scholar
  27. 27.
    Ederer F, Geisser MS, Mongin SJ, Church TR, Mandel JS. Colorectal cancer deaths as determined by expert committee and from death certificate: a comparison. The Minnesota Study. J Clin Epidemiol. 1999;52(5):447–452. doi: 10.1016/S0895-4356(99)00016-5.CrossRefPubMedGoogle Scholar
  28. 28.
    De Marco MF, Janssen-Heijnen ML, van der Heijden LH, Coebergh JW. Comorbidity and colorectal cancer according to subsite and stage: a population-based study. Eur J Cancer. 2000;36(1):95–99. doi: 10.1016/S0959-8049(99)00221-X.CrossRefPubMedGoogle Scholar
  29. 29.
    Yoshida I, Suzuki A, Vallee M, et al. Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon. Clin Gastroenterol Hepatol. 2006;4(10):1225–1231. doi: 10.1016/j.cgh.2006.07.002.CrossRefPubMedGoogle Scholar
  30. 30.
    Siddiqui AA, Maddur H, Naik S, Cryer B. The association of elevated HbA1c on the behavior of adenomatous polyps in patients with type-II diabetes mellitus. Dig Dis Sci. 2008;53(4):1042–1047. doi: 10.1007/s10620-007-9970-6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Kelly B. Stein
    • 1
    • 2
    • 4
  • Claire F. Snyder
    • 1
    • 2
    • 5
  • Bethany B. Barone
    • 2
    • 6
  • Hsin-Chieh Yeh
    • 1
    • 2
    • 7
  • Kimberly S. Peairs
    • 1
    • 8
  • Rachel L. Derr
    • 1
    • 9
  • Antonio C. Wolff
    • 3
  • Frederick L. Brancati
    • 1
    • 2
    • 10
    Email author
  1. 1.Johns Hopkins School of MedicineBaltimoreUSA
  2. 2.Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  3. 3.Department of Oncology, The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University Medical InstitutionsBaltimoreUSA
  4. 4.Division of General Internal MedicineJohns Hopkins School of MedicineBaltimoreUSA
  5. 5.Division of General Internal MedicineJohns Hopkins School of MedicineBaltimoreUSA
  6. 6.BaltimoreUSA
  7. 7.Division of General Internal MedicineJohns Hopkins School of MedicineBaltimoreUSA
  8. 8.Division of General Internal MedicineJohns Hopkins School of MedicineLuthervilleUSA
  9. 9.Center for Medicine Endocrinology and DiabetesAtlantaUSA
  10. 10.Division of General Internal MedicineWelch Center for Prevention, Epidemiology, and Clinical ResearchBaltimoreUSA

Personalised recommendations