Skip to main content

Advertisement

Log in

Insulin, Insulin Resistance, Obesity, and Cancer

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Epidemiologic studies have proposed a link between obesity, type 2 diabetes, and cancer. The pathophysiologic mechanisms involved in the development of type 2 diabetes, namely hyperinsulinemia and insulin resistance, have also been implicated in cancer development. Patients with type 2 diabetes are reported to have a worse response to cancer chemotherapy, have more complications, and have a poorer prognosis than patients with cancer without diabetes. Studies also have reported that insulin, insulin secretagogues, and metformin may have effects on tumor growth. Given the escalating worldwide prevalence of obesity and type 2 diabetes, their relationship to cancer has generated great interest and research across many fields of medicine.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CPS II:

Cancer Prevention Study II

EPIC:

European Prospective Investigation Into Cancer and Nutrition

NECSS:

National Enhanced Cancer Surveillance System

NHANES III:

Third National Health and Nutrition Examination Survey

WHI:

Women’s Health Initiative

ZODIAC-16:

Zwolle Outpatient Diabetes Project Integrating Available Care 16.

References

Papers of particular interest, published recently, have been highlighted as:• Of importance

  1. Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225–249.

    Article  PubMed  Google Scholar 

  2. Ogden CL, Carroll MD, Curtin LR, et al.: Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006, 295:1549–1555.

    Article  CAS  PubMed  Google Scholar 

  3. Haslam DW, James WP: Obesity. Lancet 2005, 366:1197–1209.

    Article  PubMed  Google Scholar 

  4. Wild S, Roglic G, Green A, et al.: Global prevalence of diabetes. Diabetes Care 2004, 27:1047–1053.

    Google Scholar 

  5. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003, 348:1625–1638.

    Article  PubMed  Google Scholar 

  6. Pan SY, Johnson KC, Ugnat A-M, et al.: Association of obesity and cancer risk in Canada. Am J Epidemiol 2004, 159:259–268.

    Article  PubMed  Google Scholar 

  7. Kuriyama S, Tsubono Y, Hozawa A, et al.: Obesity and risk of cancer in Japan. Int J Cancer 2005, 113:148–157.

    Article  CAS  PubMed  Google Scholar 

  8. Bergstrom A, Pisani P, Tenet V, et al.: Overweight as an avoidable cause of cancer in Europe. Int J Cancer 2001, 91:421–430.

    Article  CAS  PubMed  Google Scholar 

  9. • Renehan AG, Tyson M, Egger M, et al.: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008, 371:569–578. This is a large meta-analysis of articles relating obesity to certain cancers, focusing on differences between sexes and ethnicities.

    Article  PubMed  Google Scholar 

  10. Adams TD, Gress RE, Smith SC, et al.: Long-term mortality after gastric bypass surgery. N Engl J Med 2007, 357:753–761.

    Article  CAS  PubMed  Google Scholar 

  11. Kubo A, Corley DA: Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2006, 15:872–878.

    Article  PubMed  Google Scholar 

  12. Welzel TM, Graubard BI, El-Serag HB, et al.: Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin Gastroenterol Hepatol 2007, 5:1221–1228.

    Article  PubMed  Google Scholar 

  13. Patel AV, Rodriguez C, Bernstein L, et al.: Obesity, recreational physical activity, and risk of pancreatic cancer in a large U.S. cohort. Cancer Epidemiol Biomarkers Prev 2005, 14:459–466.

    Article  PubMed  Google Scholar 

  14. Larsson SC, Wolk A: Obesity and risk of non-Hodgkin’s lymphoma: a meta-analysis. Int J Cancer 2007, 121:1564–1570.

    Article  CAS  PubMed  Google Scholar 

  15. Jee SH, Ohrr H, Sull JW, et al.: Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005, 293:194–202.

    Article  CAS  PubMed  Google Scholar 

  16. Lacey J, Frisch M, Brinton L, et al.: Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States). Cancer Causes Control 2001, 12:153–161.

    Article  PubMed  Google Scholar 

  17. Olsen CM, Green AC, Whiteman DC, et al.: Obesity and the risk of epithelial ovarian cancer: a systematic review and meta-analysis. Eur J Cancer 2007, 43:690–709.

    Article  PubMed  Google Scholar 

  18. Wallstrom P, Bjartell A, Gullberg B, et al.: A prospective Swedish study on body size, body composition, diabetes, and prostate cancer risk. Br J Cancer 2009, 100:1799–1805.

    Article  CAS  PubMed  Google Scholar 

  19. Coughlin SS, Calle EE, Teras LR, et al.: Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 2004, 159:1160–1167.

    Article  PubMed  Google Scholar 

  20. Inoue M, Iwasaki M, Otani T, et al.: Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 2006, 166:1871–1877.

    Article  PubMed  Google Scholar 

  21. Sturmer T, Buring JE, Lee IM, et al.: Metabolic abnormalities and risk for colorectal cancer in the Physicians' Health Study. Cancer Epidemiol Biomarkers Prev 2006, 15:2391–2397.

    Article  PubMed  Google Scholar 

  22. Chari ST, Leibson CL, Rabe KG, et al.: Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology 2005, 129:504–511.

    PubMed  Google Scholar 

  23. Jamal MM, Yoon EJ, Vega KJ, et al.: Diabetes mellitus as a risk factor for gastrointestinal cancer among American veterans. World J Gastroenterol 2009, 15:5274–5278.

    Article  PubMed  Google Scholar 

  24. Ehrlich SF, Quesenberry CP, Van Den Eeden SK, et al.: Patients diagnosed with diabetes mellitus are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes Care 2010, 33:55–60.

    Article  PubMed  Google Scholar 

  25. Michels KB, Solomon CG, Hu FB, et al.: Type 2 Diabetes and subsequent incidence of breast cancer in the Nurses' Health Study. Diabetes Care 2003, 26:1752–1758.

    Article  PubMed  Google Scholar 

  26. Friberg E, Mantzoros CS, Wolk A: Diabetes and risk of endometrial cancer: a population-based prospective cohort study. Cancer Epidemiol Biomarkers Prev 2007, 16:276–280.

    Article  PubMed  Google Scholar 

  27. Kasper JS, Giovannucci E: A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2006, 15:2056–2062.

    Article  PubMed  Google Scholar 

  28. Stein K, Snyder C, Barone B, et al.: Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: a systematic review and meta-analysis. Dig Dis Sci 2009 Sep 3 [Epub ahead of print].

  29. Srokowski TP, Fang S, Hortobagyi GN, Giordano SH: Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer. J Clin Oncol 2009, 27:2170–2176.

    Article  PubMed  Google Scholar 

  30. Ma J, Giovannucci E, Pollak M, et al.: A prospective study of plasma C-peptide and colorectal cancer risk in men. J Natl Cancer Inst 2004, 96:546–553.

    Article  CAS  PubMed  Google Scholar 

  31. Gunter MJ, Hoover DR, Yu H, et al.: A prospective evaluation of insulin and insulin-like growth factor-1 as risk factors for endometrial cancer. Cancer Epidemiology Biomarkers Prev 2008, 17:921–929.

    Article  CAS  Google Scholar 

  32. • Gunter MJ, Hoover DR, Yu H, et al.: Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 2009, 101:48–60. This is a prospective study of women in the WHI demonstrating that endogenous insulin levels were positively correlated with breast cancer.

    CAS  PubMed  Google Scholar 

  33. LeRoith D, Roberts CT Jr: The insulin-like growth factor system and cancer. Cancer Lett 2003, 195:127–137.

    CAS  PubMed  Google Scholar 

  34. Firth SM, Baxter RC: Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 2002, 23:824–854.

    Article  CAS  PubMed  Google Scholar 

  35. Morris JK, George LM, Wu T, Wald NJ: Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies. Br J Cancer 2006, 95:112–117.

    Article  CAS  PubMed  Google Scholar 

  36. Renehan AG, Zwahlen M, Minder C, et al.: Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004, 363:1346–1353.

    Article  CAS  PubMed  Google Scholar 

  37. Rinaldi S, Cleveland R, Norat T, et al.: Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int J Cancer 2009, 126:1702–1715.

    Google Scholar 

  38. Peeters PH, Lukanova A, Allen N, et al.: Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer 2007, 14:81–90.

    Article  CAS  PubMed  Google Scholar 

  39. Bowker SL, Majumdar SR, Veugelers P, Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006, 29:254–258.

    Article  PubMed  Google Scholar 

  40. Currie C, Poole C, Gale E: The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009, 52:1766–1777.

    Article  CAS  PubMed  Google Scholar 

  41. Landman GW, Kleefstra N, van Hateren KJ, et al.: Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care 2010, 33:322–326.

    Article  CAS  PubMed  Google Scholar 

  42. Zib I, Raskin P: Novel insulin analogues and its mitogenic potential. Diabetes Obes Metab 2006, 8:611–620.

    Article  CAS  PubMed  Google Scholar 

  43. • Colhoun H, Group SE: Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia 2009, 52:1755–1765. This study has led to the current controversies surrounding insulin treatment and cancer incidence

    Article  CAS  PubMed  Google Scholar 

  44. • Hemkens L, Grouven U, Bender R, et al.: Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 2009, 52:1732. This study has led to the current controversies surrounding insulin treatment and cancer incidence.

    Article  CAS  PubMed  Google Scholar 

  45. Fierz Y, Novosyadlyy R, Vijayakumar A, et al.: Insulin sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. Diabetes 2009 Dec 3 [Epub ahead of print].

  46. Yakar S, LeRoith D, Brodt P: The role of the growth hormone/insulin-like growth factor axis in tumor growth and progression: lessons from animal models. Cytokine Growth Factor Rev 2005, 16:407–420.

    Article  CAS  PubMed  Google Scholar 

  47. Levine AJ, Feng Z, Mak TW, et al.: Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev 2006, 20:267–275.

    Article  CAS  PubMed  Google Scholar 

  48. Goodwin PJ, Ligibel JA, Stambolic V: Metformin in breast cancer: time for action. J Clin Oncol 2009, 27:3271–3273.

    Article  CAS  PubMed  Google Scholar 

  49. Gudmundsson J, Sulem P, Steinthorsdottir V, et al.: Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 2007, 39:977–983.

    Article  CAS  PubMed  Google Scholar 

  50. Aguilar-Bryan L, Bryan J: Neonatal diabetes mellitus. Endocr Rev 2008, 29:265–291.

    CAS  Google Scholar 

  51. Kurtzhals P, Schäffer L, Sørensen A, et al.: Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000, 49:999–1005.

    Article  CAS  PubMed  Google Scholar 

  52. Hennige A, Strack V, Metzinger E, et al.: Effects of new insulin analogues HMR1964 (insulin glulisine) and HMR1423 on insulin receptors. Diabetologia 2005, 48:1891–1897.

    Article  CAS  PubMed  Google Scholar 

  53. Zakikhani M, Dowling R, Fantus IG, et al.: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 2006, 66:10269–10273.

    Article  CAS  PubMed  Google Scholar 

  54. • Jiralerspong S, Palla SL, Giordano SH, et al.: Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 2009, 27:3297–3302. This is a study highlighting the potential of metformin in addition to traditional chemotherapeutic agents for breast cancer patients.

    Article  CAS  PubMed  Google Scholar 

  55. Libby G, Donnelly LA, Donnan PT, et al.: New users of metformin are at low risk of incident cancer. Diabetes Care 2009, 32:1620–1625.

    Article  CAS  PubMed  Google Scholar 

  56. Cantrell LA, Zhou C, Mendivil A, et al.: Metformin is a potent inhibitor of endometrial cancer cell proliferation—implications for a novel treatment strategy. Gynecol Oncol 2010, 116:92–98.

    Article  CAS  PubMed  Google Scholar 

  57. Rattan R, Giri S, Hartmann LC, Shridhar V: Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner. J Cell Mol Med 2009 Oct 29 [Epub ahead of print].

    Google Scholar 

  58. Kisfalvi K, Eibl G, Sinnett-Smith J, Rozengurt E: Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res 2009, 69:6539–6545.

    Article  CAS  PubMed  Google Scholar 

  59. Alimova IN, Liu B, Fan Z, et al.: Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 2009, 8:909–915.

    CAS  PubMed  Google Scholar 

Download references

Disclosure

Dr. Derek LeRoith has been a consultant/speaker for Sanofi-Aventis, Takeda, Merck, and Bristol-Myers Squibb/AstraZeneca. No other potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Derek LeRoith.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gallagher, E.J., LeRoith, D. Insulin, Insulin Resistance, Obesity, and Cancer. Curr Diab Rep 10, 93–100 (2010). https://doi.org/10.1007/s11892-010-0101-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-010-0101-y

Keywords

Navigation