Skip to main content

Advertisement

SpringerLink
Log in

Diabetes Mellitus: a Clinical Condition Associated with Metabolic Syndrome and Colorectal Cancer Risk

  • Cardiovascular Pharmacology (J Ndisang, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed carcinoma and the fourth leading cause of carcinoma deaths worldwide. Most cases of CRC occur in people aged over 50 years, often coexisting with other chronic diseases including obesity, type 2 diabetes mellitus, and cardiovascular disease. Diabetes mellitus (DM) and cancer frequently coexist. DM is associated with an increased risk for pancreatic, gastric, liver, colorectal, breast, urinary tract, and female reproductive cancers. It is hypothesized that possible biologic links between diabetes and cancer risk could be related to hormonal (insulin resistance), inflammatory, or metabolic (hyperglycemia) characteristics of DM, as well as with some antidiabetic medications. This review summarizes the current published literature regarding the association of CRC with diabetes since there is growing evidence from recent studies that this association is not random.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McGuire S. World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 2016;7:418–9.

    Article  PubMed  PubMed Central  Google Scholar 

  2. American Cancer Society. Cancer facts & figures, 2013. Atlanta: American Cancer Society; 2013.

    Google Scholar 

  3. Allen JI. Molecular biology of colon polyps and colon cancer. Surg Oncol. 1995;11:399–405.

    Article  CAS  Google Scholar 

  4. Winawer SJ, Zauber AG, Ho MN, O’Brien ML, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993;329:1977–81.

    Article  CAS  PubMed  Google Scholar 

  5. Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, et al. American Cancer Society Colorectal Cancer Advisory Group, US Multi-Society Task Force, American College of Radiology Colon Cancer Committee. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008;134:1570–95.

    Article  CAS  PubMed  Google Scholar 

  6. Hixson LJ, Fennerty MB, Sampliner RE, McGee D, Garewal H. Prospective study of the frequency and size distribution of polyps missed by colonoscopy. J Natl Cancer Inst. 1992;82:1769–72.

    Article  Google Scholar 

  7. Sakkinen PA, Wahl P, Cushman M, Lewis MR, Tracy RP. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol. 2000;152:897–907.

    Article  CAS  PubMed  Google Scholar 

  8. Reilly MP, Rader DJ. The metabolic syndrome: more than the sum of its parts? Circulation. 2003;108:1546–51.

    Article  PubMed  Google Scholar 

  9. Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J ClinNutr. 2007;86(suppl):836S–42S.

    CAS  Google Scholar 

  10. Lovic D, Stojanov V, Jakovljević B, et al. Prevalence of arterial hypertension in Serbia: PAHIS study. J Hypertens. 2013;31:2151–7.

    Article  CAS  PubMed  Google Scholar 

  11. Gerber M, Corpet D. Energy balance and cancers. Eur J Cancer Prev. 1999;8:77–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lovic D, Erdine S, BurakÇatakoǧlu A. How to estimate left ventricular hypertrophy in hypertensive patients. Anadolu Kardiyoli Derg. 2014;14:389–95.

    Article  Google Scholar 

  13. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose: associated with risk? Cancer Epidemiol Biomarkers Prev. 1994;3:687–95.

  14. Xu CX, Zhu HH, Zhu YM. Diabetes and cancer: associations, mechanisms, and implications for medical practice. World J Diabetes. 2014;5:372–80.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ontilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA. Diabetes and cancer I: risk, survival, and imlications for screening. Cancer Causes Control. 2012;23:967–81.D.

    Article  Google Scholar 

  16. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. CA Cancer J Clin. 2010;60:207–21.

    Article  PubMed  Google Scholar 

  17. García-Jiménez C, García-Martínez JM, Choccaro-Calvo A, De la Vieja A. A new link between diabetes and cancer: enhanced WNT/β-catenin signalling by high glucose. J Mol Endocrinol. 2014;52:R51–66.

    Article  CAS  PubMed  Google Scholar 

  18. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304–5.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32:1620–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Landman GW, Kleefstra N, van Hateren KJ, Groenier KH, Gans RO, Bilo HJ. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010;33:322–6.

    Article  CAS  PubMed  Google Scholar 

  21. Bruce WR, Wolever TM, Giacca A. Mechanism linking diet and colorectal cancer. The possible role of insulin resistance. Nutr Cancer. 2000;37:19–26.

    Article  CAS  PubMed  Google Scholar 

  22. Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301–16.

    Article  CAS  PubMed  Google Scholar 

  23. Colangelo LA, Gapstur SM, Gann PH, Dyer AR, Liu K. Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomark Prev. 2002;11:385–91.

    Google Scholar 

  24. Djiogue S, NwaboKamdje AH, Vecchio L, Kipanyula MJ, et al. Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer. 2013;20:R1–R17.

    Article  CAS  PubMed  Google Scholar 

  25. Novosyadlyy R, LeRoith D. Hyperinsulinemia and type 2 diabetes: impact on cancer. Cell Cycle. 2010;9:1449–50.

    Article  CAS  PubMed  Google Scholar 

  26. Alvino CL, Ong SC, McNeil KA, Delaine C, et al. Understanding the mechanism of insulin and insulin-like growth factor (IGF) receptor activation by IGF-II. PLoS One. 2011;6:e27488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fleming HE, Janzen V, Lo Celso C, Guo J, Leahy KM, Kronenberg HM, et al. Wnt signalling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008;2:274–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Stattin P, Björ O, Ferrari, Lukanova A, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007;30:561–7.

    Article  PubMed  Google Scholar 

  29. Saydah SH, Platz EA, Rifai N, Pollak MN, et al. Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2003;12:412–8.

    CAS  Google Scholar 

  30. Takahashi H, Mizuta T, Eguchi Y, Kawaguchu Y, et al. Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C. J Gastroenterol. 2011;46:790–8.

    Article  CAS  PubMed  Google Scholar 

  31. Yamasaki K, Hayashi Y, Okamoto S, Osanai M, Lee GH. Insulin-independent promotion of chemically induced hepatocellular tumor development in genetically diabetic mice. Cancer Sci. 2010;101:65–72.

    Article  CAS  PubMed  Google Scholar 

  32. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16:1103–23.

    Article  CAS  PubMed  Google Scholar 

  33. Johnson JA, Bowker SL. Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia. 2011;54:25–31.

    Article  CAS  PubMed  Google Scholar 

  34. Ward PS, Thompon CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell. 2012;21:297–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kundu JK, Surh YJ. Inflammation: gearing the journey to cancer. Mutat Res. 2008;659:15–30.

    Article  CAS  PubMed  Google Scholar 

  36. Ono M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci. 2008;99:1501–6.

    Article  CAS  PubMed  Google Scholar 

  37. Moore MM, Chua W, Charles KA, Clarke SJ. Inflammation and cancer: causes and consequences. Clin Pharmacol Ther. 2010;87:504–8.

    Article  CAS  PubMed  Google Scholar 

  38. Matsuda M, Shimomura I. Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract. 2013;7:e330–41.

    Article  PubMed  Google Scholar 

  39. Yang H, Jin X, Kei Lam CW, Yan SK. Oxidative stress and diabetes mellitus. Clin Chem Lab Med. 2011;49:1773–82.

    CAS  PubMed  Google Scholar 

  40. DiDonato JA, Mercurio F, Karin M. NF-kB and the link between inflammation and cancer. Immunol Res. 2012;246:379–400.

    Google Scholar 

  41. Hoesel B, Schmid JA. The complexity of NF-kB signaling in inflammation and cancer. Mol Cancer. 2013;12:86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bowker SL, Majumdar P, Veugelers P, Johnson JA. Increased cancer care mortality for cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29:254–8.

    Article  PubMed  Google Scholar 

  43. Monami M, Lamanna C, Balzi D, Marchionni N, Mannucci E. Sulfonylureas and cancer: a case-control study. Acta Diabetol. 2009;46:279–84.

    Article  CAS  PubMed  Google Scholar 

  44. Li D, Yeung SJ, Hassan MM, Konopleva M. Abbruzzese. Antidiabetic affect risk of pancreatic cancer. Gastroenterology. 2009;137:482–8.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Currie CJ, Poole CD, Gale EAM. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766–77.

    Article  CAS  PubMed  Google Scholar 

  46. Bodmer M, Becker C, Meier C, Jick SS, Meier CR. Use of metformin and the risk of ovarian cancer: a case-control analysis. Gynecol Oncol. 2011;132:200–4.

    Article  CAS  Google Scholar 

  47. Rattan R, Ali Fehmi R, Munkarah A. Metformin: an emerging new therapeutic option for targeting cancer stem cells and metastasis. J Oncol. 2012;2012:1–12.

    Article  CAS  Google Scholar 

  48. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009;69:7507–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lee JH, Kim TI, Jeon SM, Hong SP, Cheon JH, Kim WH. The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer. 2012;131:752–9.

    Article  CAS  PubMed  Google Scholar 

  50. Jiralerspong S, Palla S, Giordano SH, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncology. 2009;27:3297–302.

    Article  CAS  Google Scholar 

  51. Kim YH, Noh R, Cho SY, Park SJ, Jeon SM, Shin HD, et al. Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes. Intest Res. 2015;13:145–52.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Cho YM, Ko BM, Kim SH, et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intest Res. 2014;12:139–45.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Tseng CH. Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan. Eur J Endocrinol. 2012;167:409–16.1451.

    Article  CAS  PubMed  Google Scholar 

  54. Liu F, Yan L, Wang Z, Lu Y, Chu Y, Li X, et al. Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: a systematic review and meta-analysis. Oncotarget. 2017;8:16017–26.

    PubMed  Google Scholar 

  55. Schoen RE, Weissfeld JL, Kuller LH, et al. Insulin-like growth factor-1 and insulin are associated with the presence and advancement of adenomatous polyps. Gastroenterology. 2005;129:464–75.

    Article  PubMed  Google Scholar 

  56. Elwing JE, Gao F, Davidson NO, Early DS. Type 2 diabetes mellitus: the impact on colorectal adenoma risk in women. Am J Gastroenterol. 2006;101:1866–71.

    Article  PubMed  Google Scholar 

  57. Kanadiya MK, Gohel TD, Sanaka MR, Thota PN, Shubrook JH. Relationship between type-2 diabetes and use of metformin with risk of colorectal adenoma in an American population receiving colonoscopy. J Diabetes Complicat. 2013;27:463–6.

    Article  PubMed  Google Scholar 

  58. Vu HT, Ufere N, Yan Y, Wang JS, Early DS, Elwing JE. Diabetes mellitus increases risk for colorectal adenoma in younger patients. World J Gastroenterol. 2014;14:6946–52.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinic for Gastroenterology and Hepatology, Faculty of Medicine, Clinical Center Nis, Nis, Serbia

    Vesna Brzacki & Aleksandar Nagorni

  2. Cardiology Department, Asklepeion General Hospital, 16673, Athens, Greece

    Manolis Kallistratos & Athanasios Manolis

  3. Cardiology Department, Clinic for Internal Disease Intermedica, Nis, Serbia

    Dragan Lovic

Authors
  1. Vesna Brzacki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aleksandar Nagorni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manolis Kallistratos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Athanasios Manolis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dragan Lovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manolis Kallistratos.

Ethics declarations

Conflict of Interest

Vesna Brzacki, Aleksandar Nagorni, Manolis Kallistratos, Athanasios Manolis, and Dragan Lovic declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cardiovascular Pharmacology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brzacki, V., Nagorni, A., Kallistratos, M. et al. Diabetes Mellitus: a Clinical Condition Associated with Metabolic Syndrome and Colorectal Cancer Risk. Curr Pharmacol Rep 5, 205–209 (2019). https://doi.org/10.1007/s40495-019-00183-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40495-019-00183-8

Keywords

Search

Navigation