Glycated hemoglobin, diabetes treatment and cancer risk in type 2 diabetes. A case-control study
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Department of Medicine, Institute of Nursing and Health Sciences, University of Rzeszow, Poland; Diabetic Outpatient Clinic, NZOZ Beta-Med, Rzeszow, Poland
Ann Agric Environ Med. 2013;20(1):116–121
Type 2 diabetes is associated with an increased risk of some types of cancer. Diabetes treatment may also modify cancer risk.

The aim of this retrospective, case-control study was to assess whether HbA1c level and use of anti-diabetic drugs are associated with cancer development in a diabetic population.

Material and Methods:
The case group consisted of 53 patients who developed cancer after diagnosis of diabetes. They were compared with 53 diabetic subjects without cancer, strictly matched to a case group by age and gender. In both groups – apart from HbA1c and diabetes treatment – demographic data, smoking habits, comorbidities, BMI, diabetes duration, use of aspirin, antihypertensive and hypolipemic drugs were also analyzed.

Patients with cancer had a significantly higher mean HbA1c value compared with the control group, 7.83±1.26% vs. 7.30±1.08%, respectively (p=0.022). The distribution of patients in four HbA1c categories (<7.0, 7.0-7.9, 8.0-8.9 and ≥9.0%) was significantly different between the two groups (p=0.031). The probability of cancer was higher among patients with HbA1c value ≥8.0 % OR 3.160 (95% CI 1.342-7.440), p=0.013, and lower among patients using metformin, OR 0.228 (95% CI 0.083-0.633), p=0.006. The number of insulin users, insulin dose, duration of insulin treatment, and use of other anti-diabetic drugs were not significantly different between the two groups. Also, no significant differences were found between the two groups regarding other variables.

The presented case-control study indicated an important role of metabolic control and confirmed the protective role of metformin in reducing cancer risk among patients with type 2 diabetes. Contrary to other studies, insulin use was not associated with a higher risk of cancer. Other anti-diabetic drugs appeared to have a neutral impact on cancer development.

Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst. 2005; 97: 1679-1687.
Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005; 92: 2076-2083.
Wang P, Kang D, Cao W, Wang Y, Liu Z. Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2012; 28: 109-122.
Friberg E, Orsini N, Mantzoros CS, et al. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 2007; 50: 1365-1374.
Larsson SC, Mantzoros CS, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer. 2007; 121: 856-862.
Larsson SC, Orsini N, Brismar K, Wolk A. Diabetes mellitus and risk of bladder cancer: a meta-analysis. Diabetologia 2006; 49: 2819-2823.
Larsson SC, Wolk A. Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies. Diabetologia 2011; 54: 1013-1018.
Mitri J, Castillo J, Pittas AG. Diabetes and risk of Non-Hodgkin’s lymphoma. A meta-analysis of observational studies. Diabetes Care. 2008; 31: 2391-2397.
Lee S-A. Gene-diet interaction on cancer risk in epidemiological studies. J Prev Med Public Health. 2009; 42: 360-370.
Dąbrowski M. Cukrzyca a nowotwory (Diabetes and cancer). Diabet Prakt. 2010; 11: 54-63 (in Polish).
Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010; 33: 1674-1685.
Noto H, Tsujimoto T, Sasazuki T, Noda M. Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr Pract. 2011; 17: 616-628.
Johnson JA, Carstensen B, Witte D, Bowker SL, Lipscombe L, Renehan AG. Diabetes and cancer (1): evaluating a temporal relationship between type 2 diabetes and cancer incidence. Diabetologia 2012; 55: 1607-1618.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg Effect: The metabolic requirements of cell proliferation. Science 2009; 324: 1029-1033.
Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with Glucagon-Like Peptide-1–based therapies. Gastroenterology 2011; 141: 150-156.
Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011; 34: 916-922.
Neumann A, Weill A, Ricordeau P, Fagot JP, Alla F, Allemand H. Pioglitazone and risk of bladder cancer among diabetic patients in France: a population-based cohort study. Diabetologia 2012; DOI 10.1007/s00125-012-2538-9 (accessed: 20 June 2012).
Heuson JC, Legros N, Heimann R. Influence of insulin administration on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in intact, oophorectomized, and hypophysectomized rats. Cancer Res. 1972; 32: 233-238.
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: 945-952.
Stattin P, Björ O, Ferrari P, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007; 30: 561-567.
Stocks T, Rapp K, Bjørge T, et al. Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (Me-Can): analysis of six prospective cohorts. PLoS Med. 2009 Dec; 6(12): e1000201. Epub 2009 Dec 22.
Stocks T, Lukanova A, Johansson M, et al. Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes. 2008; 32: 304-314.
Khaw K-T, Wareham N, Bingham S, Luben R, Welch A, Day N. Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into Cancer–Norfolk Study. Cancer Epidemiol Biomarkers Prev. 2004; 13: 915-919.
Rinaldi S, Rohrmann S, Jenab M, et al. Glycosylated hemoglobin and risk of colorectal cancer in men and women, the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev. 2008; 17: 3108-3115.
Joshu CE, Prozment AE, Dluzniewski PJ, et al. Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990-2006. Int J Cancer. doi: 10.1002/ijc.27394, published online 10 Feb 2012. (accessed 20 June 2012).
Donadon V, Balbi M, Valent F, Avogaro A. Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenetrol. 2010; 16: 3025-3032.
Yang Y-X, Habel LA, Capra AM, et al. Serial glycosylated hemoglobin levels and risk of colorectal neoplasia among patients with type 2 diabetes mellitus. Cancer Epidemiol Biomarkers Prev. 2010; 19: 3027-3036.
Lin J, Ridker PM, Rifai N, et al. A prospective study of hemoglobin A1c concentrations and risk of breast cancer in women. Cancer Res. 2006; 66: 2869-2875.
Becker S, Dossus L, Kaaks R. Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. Arch Physiol Biochem. 2009; 115: 86-96.
Riehl A, Németh J, Angel P, Hess J. The receptor RAGE: Bridging inflammation and cancer. Cell Commun Signal. 2009; 7: 12; doi:10.1186/1478-811X-7-12 (accessed 20 June 2012).
Polskie Towarzystwo Diabetologiczne. Zalecenia kliniczne dotyczące postępowania u chorych na cukrzycę, 2012. Diabetologia Klin. 2012; 1 (supl. A) (in Polish).
American Diabetes Association. Clinical practice recommendations 2012. Diabetes Care. 2012; 35 (Suppl.1).
Inzucchi SE, Bergenstal RM, Buse JB,et al. Management of hyperglycemia in type 2 diabetes: a patient centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012; 55: 1577-1596.
Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann NY Acad Sci. 2011; 1243: 54-68.
Aljada A, Mousa SA. Metformin and neoplasia: Implications and indications. Pharmacol Ther. 2012; 133: 108-115.
Janghorbani M, Dehghani M, Salehi-Marzijarani M. Systematic review and meta-analysis of insulin therapy and risk of cancer. Horm Cancer. 2012; DOI: 10.1007/s12672-012-0112-z, April 24 (accessed 20 June 2012).
Bhartia M, Tahrani AA, Barnett AH. SGLT-2 inhibitors in development for type 2 diabetes treatment. Rev Diabet Stud. 201; 8: 348-354.
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371: 569-578.