Diabetes mellitus and malignancies

Czech version

Authors: Jiří Petera ¹; Alena Šmahelová ²
Authors‘ workplace: Klinika onkologie a radioterapie LF UK a FN Hradec Králové, přednosta prof. MUDr. Jiří Petera, Ph. D. ¹; III. interní gerontometabolická klinika LF UK a FN Hradec Králové, přednosta prof. MUDr. Luboš Sobotka, CSc. ²
Published in: Vnitř Lék 2014; 60(Suppl 2): 69-74
Category: 70th Birthday - prof. MUDr. Jiří Vorlíček, CSc.

Overview

The epidemiological studies have proven an increased incidence of cancer in patients with diabetes and the negative effect of diabetes on their prognosis. The relation to type 2 diabetes was found in hepatic, pancreatic and endometrial malignancies, in colorectal, breast and bladder cancers. Diabetes as well as malignancies are multifactorial diseases with a number of common risk factors: age, gender, race, overweight and obesity, diet, physical activity. A higher incidence of malignancies in diabetic patients is not only a result of sharing these risk factors, as diabetes itself predisposes to carcinoma development. Possible mechanisms producing this effect include hyperinsulinemia, hyperglycemia, oxidative stress, chronic inflammation, obesity related factors and effect of diabetic complications. The development of malignancies in diabetics is also affected by the diabetes treatment. Exogenous insulin and its analogues and stimulators of insulin secretion are linked to an increased risk of cancer while insulin sensitizers to its decrease. Special attention is given to metformin which, apart from the indirect effect by influencing the levels of insulin and glycemia, has a direct anticancerogenic effect. In the clinical practice, it is necessary to give attention to the screening of diabetes related tumours, consistent glycemic control and choice of appropriate diabetes treatment in patients with a high cancer risk.

Key words:
clinical practice – diabetes mellitus – effects of diabetes treatment – malignancies

Sources

1. Lopez AD, Mathers CD, Ezzati M et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006; 367(9524): 1747–1757.

2. National Diabetes Fact Sheet: General information and national estimates on diabetes in the United States, 2007. Centers for disease control and prevention: Atlanta, GA 2008. Dostupné z WWW: <http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf>.

3. Noto H, Tsujimoto T, Sasazuki T et al. Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr Pract 2011; 17(4): 616–628.

4. Noto H, Goto A, Tsujimoto T et al. Latest insights into the risk of cancer in diabetes. J Diabetes Investig 2013; 4(3): 225–232.

5. Barone BB, Yeh HC, Snyder CF et al. Long term all cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 2008; 300(23): 2754–2764.

6. 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.

7. 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(17): 1871–1877.

8. Stattin P, Björ O, Ferrari P et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care 2007; 30(3): 561–567.

9. Rapp K, Schroeder J, Klenk J et al. Fasting blood glucose and cancer risk in a cohort of more than 140 000 adults in Austria. Diabetologia 2006; 49(5): 945–952.

10. Green A, Jensesn OM. Frequency of cancer among insulin-treated diabetic patients in Denmark. Diabetologia 1985; 28(3): 128–130.

11. Zendehdel K, Nyrén O, Őstenson CG et al. Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst 2003; 95(23): 1797–1800.

12. Sciacca L, Vigneri R, Tumminia A et al. Clinical and molecular mechanisms favoring cancer initiaion and progression in diabetic patients. Nutr Metab Cardiovasc Dis 2013; 23(9): 808–815.

13. Taubes G. Cancer research. Unraveling the obesity – cancer connection. Science 2012; 335 (6064): 28, 30–32.

14. Johnson JA, Bowker SL. Intensive glycaemic control and risk in type 2 diabetes: a metaanalysis of major trials. Diabetologia 2011; 54(1): 25–31.

15. Yang X, Ko GT, Wy H et al. Associations of hyperglycaemia and insulin usage with the risk of cancer in type 2 diabetes: the Hong Kong Diabetes Registry. Diabetes 2010; 59(5): 1254–1260.

16. Wu Y, Zhou BP. Inflammation: a driving force speeds cancer metastasis. Cell Cycle 2009; 8(20): 3267–3273.

17. Mantovani A, Allavena P, Sica A et at. Cancer-related inflammation. Nature 2008; 454 (7203): 436–444.

18. Kasem S. NF-kappaB function as a tumour promoter in inflammation-associated cancer. Nature 2004; 431(7007): 461–466.

19. Jee SH, Ohrr H, Sull JW et al. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005; 293(2): 194–202.

20. Vigneri P, Frasca F, Sciacca L et al. Diabetes and cancer. Endocr Relat Cancer 2009; 16(4): 1103–1123.

21. Wong P, Weiner MG, Hwang WT et al. Insulin therapy and colorectal adenomas in patients with diabetes mellitus. Cancer Epidemiol Biomarkers Prev 2012; 21(10): 1833–1840.

22. Zhang ZH, Su PY, Hao JH et al. The role in preexisting diabetes mellitus on incidence and mortality of endometrial cancer: a meta-analysis of prospective cohort studies. Int J Gynecol Cancer 2013; 23(2): 234–303.

23. James RE, Lukanova A, Dossus L et al. Postmenopausal serum sex steroids and risk of hormone recepro-positive and -negative breast cancer: a nested case-control study. Cancer Prev Res (Phila) 2011; 4(10): 1626–1653.

24. Sipahi I, Debanne SM, Rowland DY et al. Angiotensin-receptor blockade and a risk of cancer: meta-analysis of randomized controlled trials. Lancet Oncology 2010; 11(7): 627–636.

25. Frayling TM, Colhoun H, Florez JC. A genetic link between type 2 diabetes and prostate cancer. Diabetologia 2008; 51(10): 1757–1760.

26. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009; 52(9): 1766–1777.

27. Baur DM, Klotsche J, Hamvik OP et al. Type 2 diabetes mellitus and medication for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort. Metabolism 2011; 60(10): 1363–1371.

28. Mannucci E, Monami M, Balzi D et al. Doses of insulin and its analogues and cancer occurrence in insulin treated type 2 diabetic patients. Diabetes Care 2010; 33(9): 1997–2003.

29. Hemkens LG, 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(9): 1732–1754.

30. Colhoun HM. SDRN Epidemiology Group. Use of insuline glargine and cancer incidence in Scotland: a study form the Scottish Diabetes Research Notwork Epidemiology Group. Diabetologia 2009; 52(9): 1755–1765.

31. Bowker SL, Majumdar SR, Veugelers P et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006; 29(2): 254–258.

32. Taubes G. Cancer Research. Cancer preention with a diabetes pill? Science 2012; 335(6064): 29.

33. 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(2): 322–326.

34. He X, Esteva FJ, Ensor J et al. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol 2011; 23(7): 1771–1780.

35. Currie CJ, Poole CD, Jenkins-Jones S et al. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes care 2002; 35(2): 299–304.

36. 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(20): 3297–3302.

37. Noto H, Goto A, Tsujimoto T et al. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS ONE 2012; 7(3): e33411. Dostupné z DOI: <http://doi: 10.1371/journal.pone.0033411>.

38. McFarland MS, Cripps R Diabetes mellitus and increased risk of cancer: focus on metformin and the insulin analogs. Pharmacotherapy 2010; 30(11): 1159–1178.

39. Tesařová P. Metformin – nová hvězda onkologické léčby? Onkologie 2012; 6(2): 82–84.

40. Tesařová P. Diabetes mellitus a zhoubný nádor. Onkologie 2011; 5(3): 163–168.

41. Govindarajan, Ratnasinghe L, Simmons DL et al. Thiazolidinediones and the risk of lung, prostate and colon cancer in patients with diabetes. J Clin Oncol 2007; 25(12): 1476–1481.

42. Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427–2443.

43. Kalakota K, Liauw SL. Toxicity after external beam radiotherapy for prostate cancer: an analysis of late morbidity in men with diabetes mellitus. Urology 2013; 81(6): 1196–1201.

44. Giovannucci E, Harlan DFM, Archer MC et al. Diabetes and cancer: a consensus report. Diabetes Care 2010; 33(7): 1674–1685.