Diabetes and cancer: two diseases with obesity as a common risk factor

S K Garg, H Maurer, K Reed, R Selagamsetty, S K Garg, H Maurer, K Reed, R Selagamsetty

Abstract

There is a growing body of evidence to support a connection between diabetes (predominantly type 2), obesity and cancer. Multiple meta-analyses of epidemiological data show that people with diabetes are at increased risk of developing many different types of cancers, along with an increased risk of cancer mortality. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinaemia, enhanced inflammatory processes, dysregulation of sex hormone production and hyperglycaemia. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Indeed, obesity is associated with an increased risk of cancer and diabetes. Abdominal adiposity has been shown to play a role in creating a systemic pro-inflammatory environment, which could result in the development of both diabetes and cancer. Here, we examine the relationship between diabetes, obesity and cancer, and investigate the potential underlying causes of increased cancer risk in individuals with diabetes. Current treatment recommendations for reducing the overall disease burden are also explored and possible areas for future research are considered.

Keywords: antidiabetic drug; diabetes complications; diabetes mellitus; type 2 diabetes.

© 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Interrelationship between pathological mechanisms and modifiable and non-modifiable risk factors involved in diabetes, obesity and cancer. IGF, insulin-like growth factor.
Figure 2
Figure 2
Possible mechanism by which metformin may be able to inhibit cancer cell growth. AMPK, adenosine monophosphate-activated protein kinase; ER, endoplasmic reticulum; IGF, insulin-like growth factor; LKB1, liver kinase B1; mTOR, mammalian target of rapamycin; TSP, thrombospondin; UPR, unfolded protein response. Adapted with permission from Ref. .

References

    1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367:1747–1757.
    1. Jalving M, Gietema JA, Lefrandt JD, et al. Metformin: taking away the candy for cancer? Eur J Cancer. 2010;46:2369–2380.
    1. Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–1685.
    1. Johnson JA, Pollak M. Insulin, glucose and the increased risk of cancer in patients with type 2 diabetes. Diabetologia. 2010;53:2086–2088.
    1. LeRoith D, Novosyadlyy R, Gallagher EJ, Lann D, Vijayakumar A, Yakar S. Obesity and type 2 diabetes are associated with an increased risk of developing cancer and a worse prognosis; epidemiological and mechanistic evidence. Exp Clin Endocrinol Diabetes. 2008;116(Suppl. 1):S4–S6.
    1. 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;52:1732–1744.
    1. Bowker SL, Novosyadlyy R, Gallagher EJ, Lann D, Vijayakumar A, Yakar S. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29:254–258.
    1. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766–1777.
    1. Jonasson JM, Ljung R, Talback M, Haglund B, Gudbjornsdottir S, Steineck G. Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Diabetologia. 2009;52:1745–1754.
    1. Boyle P. Philadelphia, PA: ADA Scientific Sessions; 2012. Northern European Database Study of Insulin and Cancer Risk.
    1. Habel LA. Philadelphia, PA: ADA Scientific Sessions; 2012. Results from Kaiser-Permanente Collaboration.
    1. Sturmer T. Philadelphia, PA: ADA Scientific Sessions; 2012. Cancer link with insulin-data from the U.S. and Northern Europe.
    1. Boyle P, Koechlin A, Bonio M, Robertson C, Bolli G, Rosenstock J. Philadelphia, PA: ADA Scientific Sessions; 2012. Updated meta-analysis of cancer risk among users of insulin glargine.
    1. ORIGIN Trial Investigators. Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319–328.
    1. 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.
    1. 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;91:542–547.
    1. Campbell PT, Deka A, Jacobs EJ, et al. Prospective study reveals associations between colorectal cancer and type 2 diabetes mellitus or insulin use in men. Gastroenterology. 2010;139:1138–1146.
    1. 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.
    1. Parazzini F, La Vecchia C, Negri E, et al. Diabetes and endometrial cancer: an Italian case-control study. Int J Cancer. 1999;81:539–542.
    1. Silverman DT, Schiffman M, Everhart J, et al. Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer. 1999;80:1830–1837.
    1. Calle EE, Murphy TK, Rodriguez C, Thun MJ, Heath CWJR. Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control. 1998;9:403–410.
    1. Ben Q, Cai Q, Li Z, et al. The relationship between new-onset diabetes mellitus and pancreatic cancer risk: a case-control study. Eur J Cancer. 2011;47:248–254.
    1. Larsson SC, Orsini N, Brismar K, Wolk A. Diabetes mellitus and risk of bladder cancer: a meta-analysis. Diabetologia. 2006;49:2819–23.
    1. Larsson SC, Mantzoros CS, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer. 2007;121:856–862.
    1. Wolf I, Sadetzki S, Gluck I, et al. Association between diabetes mellitus and adverse characteristics of breast cancer at presentation. Eur J Cancer. 2006;42:1077–1082.
    1. Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:1679–1687.
    1. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. Lancet Oncol. 2005;6:103–111.
    1. Friberg E, Orsini N, Mantzoros CS, Wolk A. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia. 2007;50:1365–1374.
    1. El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol. 2006;4:369–380.
    1. 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.
    1. Chao C, Page JH. Type 2 diabetes mellitus and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis. Am J Epidemiol. 2008;168:471–480.
    1. Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 1995;273:1605–1609.
    1. Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005;92:2076–2083.
    1. Bonovas S, Filioussi K, Tsantes A. Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia. 2004;47:1071–1078.
    1. Kasper JS, Giovannucci E. A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:2056–2062.
    1. Johnson JA, Carstensen B, Witte D, et al. Diabetes and cancer (1): evaluating the temporal relationship between type 2 diabetes and cancer incidence. Diabetologia. 2012;55:1607–1618.
    1. Turner EL, Lane JA, Donovan JL, et al. Association of diabetes mellitus with prostate cancer: nested case-control study (Prostate testing for cancer and treatment study) Int J Cancer. 2011;128:440–446.
    1. Bansal D, Bhansali A, Kapil G, Undela K, Tiwari P. Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 2013;16:151–158.
    1. Pierce BL. Why are diabetics at reduced risk for prostate cancer? A review of the epidemiologic evidence. Urol Oncol. 2012;30:735–743.
    1. Liu JH, Li HW, Tong M, Li M, Na YQ. Genetic risk factors of prostate cancer in Han nationality population in Northern China and a preliminary study of the reason of racial difference in prevalence of prostate cancer. Zhonghua Yi Xue Za Zhi. 2004;84:364–8.
    1. Hara N. Prostate carcinogenesis with diabetes and androgen-deprivation-therapy-related diabetes: an update. Exp Diabetes Res. 2012;2012:801610.
    1. Li Q, et al. History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study. Cancer Causes Control. 2010;21:1025–1032.
    1. Tseng CH, Chen CJ, Landolph JR., Jr Diabetes and cancer: epidemiological, clinical, and experimental perspectives. Exp Diabetes Res. 2012;2012:101802.
    1. Al-Delaimy WK, Natarajan L, Rock CL, Sun S, Flatt SW, Pierce JP. Insulin-like growth factor I, insulin-like growth factor I binding protein 1, insulin, glucose, and leptin serum levels are not influenced by a reduced-fat, high-fiber diet intervention. Cancer Epidemiol Biomarkers Prev. 2006;15:1238–1239.
    1. Stattin P, Bylund A, Rinaldi S, et al. Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. J Natl Cancer Inst. 2000;92:1910–1917.
    1. Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998;279:563–566.
    1. Nimptsch K, Kenfield S, Jensen MK, et al. Dietary glycemic index, glycemic load, insulin index, fiber and whole-grain intake in relation to risk of prostate cancer. Cancer Causes Control. 2011;22:51–61.
    1. Endogenous Hormones and Prostate Cancer Collaborative Group. Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100:170–183.
    1. Kasper JS, Liu Y, Pollak MN, Rifai N, Giovannucci E. Hormonal profile of diabetic men and the potential link to prostate cancer. Cancer Causes Control. 2008;19:703–710.
    1. Laaksonen DE, Niskanen L, Punnonen K, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004;27:1036–1041.
    1. Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134:981–987.
    1. Ben Q, Xu M, Ning X, et al. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer. 2011;47:1928–1937.
    1. Huang S, Ye H, Wu W, et al. Research on the relationships between pancreatic cancer and hyperglycemia in Chinese populations. J Diabetes Invest. 2013;4:45–52.
    1. Cui Y, Andersen DK. Diabetes and pancreatic cancer. Endocr Relat Cancer. 2012;19:F9–F26.
    1. Lipworth L, Zucchetto A, Bosetti C, et al. Diabetes mellitus, other medical conditions and pancreatic cancer: a case-control study. Diabetes Metab Res Rev. 2011;27:255–261.
    1. Grote VA, Rohrmann S, Nieters A, et al. Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Diabetologia. 2011;54:3037–3046.
    1. Pannala R, Basu A, Petersen GM, Chari ST. New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol. 2009;10:88–95.
    1. 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;159:1160–1167.
    1. Lam EK, Batty GD, Huxley RR, et al. Associations of diabetes mellitus with site-specific cancer mortality in the Asia-Pacific region. Ann Oncol. 2011;22:730–738.
    1. Zhou XH, Qiao Q, Zethelius B, et al. Diabetes, prediabetes and cancer mortality. Diabetologia. 2010;53:1867–1876.
    1. 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;300:2754–2764.
    1. 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;120:1986–1992.
    1. Maruthur NM, Bolen S, Brancati FL, Clark JM. Obesity and mammography: a systematic review and meta-analysis. J Gen Intern Med. 2009;24:665–677.
    1. Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med. 2008;359:2105–2120.
    1. Duggan C, Irwin ML, Xiao L, et al. Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol. 2011;29:32–39.
    1. Erickson K, Patterson RE, Flatt SW, et al. Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol. 2011;29:54–60.
    1. Lipscombe LL, Fischer HD, Yun L, et al. Association between tamoxifen treatment and diabetes: a population-based study. Cancer. 2012;118:2615–2622.
    1. Beckman TJ, Cuddihy RM, Scheitel SM, Naessens JM, Killian JM, Pankratz VS. Screening mammogram utilization in women with diabetes. Diabetes Care. 2001;24:2049–2053.
    1. Richardson LC, Pollack LA. Therapy insight: Influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol. 2005;2:48–53.
    1. McBean AM, Yu X. The underuse of screening services among elderly women with diabetes. Diabetes Care. 2007;30:1466–1472.
    1. Fleming ST, Pursley HG, Newman B, Pavlov D, Chen K. Comorbidity as a predictor of stage of illness for patients with breast cancer. Med Care. 2005;43:132–140.
    1. Maruthur NM, Bolen SD, Brancati FL, Clark JM. The association of obesity and cervical cancer screening: a systematic review and meta-analysis. Obesity (Silver Spring) 2009;17:375–381.
    1. 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.
    1. Meyerhardt JA, Catalano PJ, Haller DG, et al. Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol. 2003;21:433–440.
    1. Weiser MA, Cabanillas ME, Konopleva M, et al. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004;100:1179–1185.
    1. Barone BB, Yeh HC, Snyder CF, et al. Postoperative mortality in cancer patients with preexisting diabetes: systematic review and meta-analysis. Diabetes Care. 2010;33:931–939.
    1. Perks CM, Vernon EG, Rosendahl AH, Tonge D, Holly JM. IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells. Oncogene. 2007;26:5966–5972.
    1. Pollak M. Do cancer cells care if their host is hungry? Cell Metab. 2009;9:401–403.
    1. Gallagher EJ, Fierz Y, Ferguson RD, LeRoith D. The pathway from diabetes and obesity to cancer, on the route to targeted therapy. Endocr Pract. 2010;16:864–873.
    1. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8:915–928.
    1. Frasca F, Pandini G, Sciacca L, et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008;114:23–37.
    1. Papa V, Belfiore A. Insulin receptors in breast cancer: biological and clinical role. J Endocrinol Invest. 1996;19:324–333.
    1. Godsland IF. Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci (Lond) 2010;118:315–332.
    1. Ibrahim YH, Yee D. Insulin-like growth factor-I and cancer risk. Growth Horm IGF Res. 2004;14:261–269.
    1. Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab. 2006;17:328–336.
    1. Frasca F, Pandini G, Scalia P, et al. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol. 1999;19:3278–3288.
    1. Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells. Diabetes Metab Res Rev. 2009;25:41–49.
    1. Wolf I, Rubinek T. Diabetes mellitus and breast cancer. In: Masur K, Thevenod F, Zanker KS, editors. Diabetes and cancer. Basel: Karger; 2008. pp. 97–113.
    1. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793–1801.
    1. van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev. 2009;18:2569–2578.
    1. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–444.
    1. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA. 2005;293:194–202.
    1. Zeng L, Biernacka KM, Holly JM, et al. Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. Endocr Relat Cancer. 2010;17:539–551.
    1. Villarreal-Garza C, Shaw-Dulin R, Lara-Medina F, et al. Impact of diabetes and hyperglycemia on survival in advanced breast cancer patients. Exp Diabetes Res. 2012;2012:732027.
    1. Turturro F, Friday E, Welbourne T. Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231. BMC Cancer. 2007;7:96.
    1. Pandey V, Chaube B, Bhat MK. Hyperglycemia regulates MDR-1, drug accumulation and ROS levels causing increased toxicity of carboplatin and 5-fluorouracil in MCF-7 cells. J Cell Biochem. 2011;112:2942–2952.
    1. Sadoff L. Overwhelming 5-fluorouracil toxicity in patients whose diabetes is poorly controlled. Am J Clin Oncol. 1998;21:605–607.
    1. Brunello A, Kapoor R, Extermann M. Hyperglycemia during chemotherapy for hematologic and solid tumors is correlated with increased toxicity. Am J Clin Oncol. 2011;34:292–296.
    1. Kung SS, Goldberg ND, Dahl JL, Parks REJR, Kline BE. Potentiation of 5-Fluorouracil Inhibition of Flexner-Jobling Carcinoma by Glucose. Science. 1963;141:627–628.
    1. Feng J-P, Yuan X-L, Li M, et al. Secondary diabetes associated with 5-fluorouracil-based chemotherapy regimens in non-diabetic patients with colorectal cancer: results from a single-centre cohort study. Colorectal Dis. 2012;15:27–33.
    1. Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract. 2009;15:469–474.
    1. Pennell NA. Selection of chemotherapy for patients with advanced non-small cell lung cancer. Cleve Clin J Med. 2012;79(Electronic Suppl 1):eS46–50.
    1. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16:1103–1123.
    1. Feller S, Boeing H, Pischon T. Body mass index, waist circumference, and the risk of type 2 diabetes mellitus: implications for routine clinical practice. Dtsch Arztebl Int. 2010;107:470–476.
    1. Pischon T, Boeing H, Weikert S, et al. Body size and risk of prostate cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2008;17:3252–3261.
    1. Berrington de Gonzalez A, Spencer EA, Bueno-de-Mesquita HB, et al. Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2006;15:879–885.
    1. 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.
    1. 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.
    1. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15:556–565.
    1. Steffen A, Schulze MB, Pischon T, et al. Anthropometry and esophageal cancer risk in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2009;18:2079–2089.
    1. Friedenreich C, Norat T, Steindorf K, et al. Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2006;15:2398–2407.
    1. Pischon T, Lahmann PH, Boeing H, et al. Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC) J Natl Cancer Inst. 2006;98:920–931.
    1. Lahmann PH, Hoffmann K, Allen N, et al. Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC) Int J Cancer. 2004;111:762–771.
    1. Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci. 2012;1271:37–43.
    1. Griggs JJ, Sorbero ME, Lyman GH. Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Med. 2005;165:1267–1273.
    1. Wong JR, Gao Z, Merrick S, et al. Potential for higher treatment failure in obese patients: correlation of elevated body mass index and increased daily prostate deviations from the radiation beam isocenters in an analysis of 1,465 computed tomographic images. Int J Radiat Oncol Biol Phys. 2009;75:49–55.
    1. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579–591.
    1. Landman GW, Van Hateren KJ, Kleefstra N, Bilo HJ. The relationship between obesity and cancer mortality in type 2 diabetes: a ten-year follow-up study (ZODIAC-21) Anticancer Res. 2010;30:681–682.
    1. Williams GP. The role of oestrogen in the pathogenesis of obesity, type 2 diabetes, breast cancer and prostate disease. Eur J Cancer Prev. 2010;19:256–271.
    1. Alokail MS, Al-Daghri NM, Al-Attas OS, Hussain T. Combined effects of obesity and type 2 diabetes contribute to increased breast cancer risk in premenopausal women. Cardiovasc Diabetol. 2009;8:33.
    1. Ali AS, Ali S, Ahmad A, Bao B, Philip PA, Sarkar FH. Expression of microRNAs: potential molecular link between obesity, diabetes and cancer. Obes Rev. 2011;12:1050–1062.
    1. Percik R, Stumvoll M. Obesity and cancer. Exp Clin Endocrinol Diabetes. 2009;117:563–566.
    1. Stattin P, Lukanova A, Biessy C, et al. Obesity and colon cancer: does leptin provide a link? Int J Cancer. 2004;109:149–152.
    1. Fenton JI, Hord NG, Lavigne JA, Perkins SN, Hursting SD. Leptin, insulin-like growth factor-1, and insulin-like growth factor-2 are mitogens in ApcMin/+ but not Apc+/+ colonic epithelial cell lines. Cancer Epidemiol Biomarkers Prev. 2005;14:1646–1652.
    1. Wellen KE, Thompson CB, et al. Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell. 2010;40:323–332.
    1. Bao B, Wang Z, Li Y, et al. The complexities of obesity and diabetes with the development and progression of pancreatic cancer. Biochim Biophys Acta. 2011;1815:135–146.
    1. Ramos EJ, Xu Y, Romanova I, et al. Is obesity an inflammatory disease? Surgery. 2003;134:329–335.
    1. Fogarty AW, Glancy C, Jones S, Lewis SA, McKeever TM, Britton JR. A prospective study of weight change and systemic inflammation over 9 y. Am J Clin Nutr. 2008;87:30–35.
    1. Tsujinaka S, Konishi F, Kawamura YJ, et al. Visceral obesity predicts surgical outcomes after laparoscopic colectomy for sigmoid colon cancer. Dis Colon Rectum. 2008;51:1757–1765.
    1. Balentine CJ, Wilks J, Robinson C, et al. Obesity increases wound complications in rectal cancer surgery. J Surg Res. 2010;163:35–39.
    1. Makino T, Shukla PJ, Rubino F, Milsom JW. The impact of obesity on perioperative outcomes after laparoscopic colorectal resection. Ann Surg. 2012;255:228–236.
    1. Park JW, Lim SW, Choi HS, Jeong SY, Oh JH, Lim SB. The impact of obesity on outcomes of laparoscopic surgery for colorectal cancer in Asians. Surg Endosc. 2010;24:1679–1685.
    1. Whitlock K, Gill RS, Birch DW, Karmali S. The association between obesity and colorectal cancer. Gastroenterol Res Pract. 2012;2012:768247.
    1. Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2012;30:1553–1561.
    1. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 2006;66:10269–10273.
    1. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007;67:10804–10812.
    1. Burton JD, Goldenberg DM, Blumenthal RD. Potential of peroxisome proliferator-activated receptor gamma antagonist compounds as therapeutic agents for a wide range of cancer types. PPAR Res. 2008;2008:494161.
    1. Tachibana K, Yamasaki D, Ishimoto K, Doi T. The role of PPARs in cancer. PPAR Res. 2008;2008:102737.
    1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193–203.
    1. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009;137:482–488.
    1. Bowker SL, Yasui Y, Veugelers P, Johnson JA. Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Diabetologia. 2010;53:1631–1637.
    1. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304–1305.
    1. 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;32:1620–1625.
    1. Kourelis TV, Siegel RD. Metformin and cancer: new applications for an old drug. Med Oncol. 2012;29:1314–1327.
    1. Wilmik J. Metformin combined with chemotherapy for pancreatic cancer. Available from URL: .
    1. Stevens R, Ali R, Bankhead CR, et al. Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. Diabetologia. 2012;55:2593–2603.
    1. Bosco JL, Antonsen S, Sorensen HT, Pedersen L, Lash TL. Metformin and incident breast cancer among diabetic women: a population-based case-control study in Denmark. Cancer Epidemiol Biomarkers Prev. 2011;20:101–111.
    1. Little MW, Pugh TF, Carey FJ, et al. The potential protective effect of metformin against pancreatic cancer: preliminary results from a case–control study in two UK centres. Gut. 2011;60(Suppl 1):A78–A79.
    1. 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;33:1997–2003.
    1. Yang YX, Hennessy S, Lewis JD. Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology. 2004;127:1044–1050.
    1. Colhoun HM SDRN Epidemiology Group. Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia. 2009;52:1755–1765.
    1. Pocock SJ, Smeeth L. Insulin glargine and malignancy: an unwarranted alarm. Lancet. 2009;374:511–513.
    1. Smith U, Gale EA. Does diabetes therapy influence the risk of cancer? Diabetologia. 2009;52:1699–1708.
    1. Rosenstock J, Fonseca V, McGill JB, et al. Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: findings from a 5 year randomised, open-label study. Diabetologia. 2009;52:1971–1973.
    1. Home PD, Lagarenne P. Combined randomised controlled trial experience of malignancies in studies using insulin glargine. Diabetologia. 2009;52:2499–2506.
    1. Yang X, Ko GT, So WY, et al. Associations of hyperglycemia and insulin usage with the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry. Diabetes. 2010;59:1254–1260.
    1. Dejgaard A, Lynggaard H, Rastam J, Krogsgaard Thomsen M. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia. 2009;52:2507–2512.
    1. Grimaldi-Bensouda L, Marty M, Pollak M, et al. The international study of insulin and cancer. Lancet. 2010;376:769–770.
    1. 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.
    1. Monami M, Lamanna C, Marchionni N, Mannucci E. Rosiglitazone and risk of cancer: a meta-analysis of randomized clinical trials. Diabetes Care. 2008;31:1455–1460.
    1. McIntosh CH, Demuth HU, Pospisilik JA, Pederson R. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents? Regul Pept. 2005;128:159–165.
    1. Stulc T, Sedo A. Inhibition of multifunctional dipeptidyl peptidase-IV: is there a risk of oncological and immunological adverse effects? Diabetes Res Clin Pract. 2010;88:125–131.
    1. Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS. DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells. Regul Pept. 2006;137:147–155.
    1. 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.
    1. US Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) (formerly AERS) 2010. [cited 2013 9 April 2013]; Available from URL: .
    1. Engel SS, Williams-Herman DE, Golm GT, et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract. 2010;64:984–990.
    1. Tatarkiewicz K, Smith PA, Sablan EJ, et al. Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents. Am J Physiol Endocrinol Metab. 2010;299:E1076–E1086.
    1. Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 98:271–284.
    1. Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care. 2012–2010;33:2349–2354.
    1. Wenten M, Gaebler JA, Hussein M, et al. Relative risk of acute pancreatitis in initiators of exenatide twice daily compared with other anti-diabetic medication: a follow-up study. Diabet Med. 2012;29:1412–1418.
    1. Dore DD, Bloomgren GL, Wenten M, et al. A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab. 2011;13:559–566.
    1. Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin. 2009;25:1019–1027.
    1. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. Vol. 173. JAMA Intern Med: 2013. pp. 534–539.
    1. Gier B, Butler PC. Glucagon like peptide 1-based drugs and pancreatitis: clarity at last, but what about pancreatic cancer? JAMA Intern Med. 173:539–541.
    1. Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013;62:2595–2604.
    1. Novo Nordisk. Denmark: Novo Nordisk: >Bagsvaerd; 2011. Victoza® (liraglutide [rDNA origin] injection)solution for subcutaneous use: US prescribing information.
    1. Parks M, Rosebraugh C. Weighing risks and benefits of liraglutide--the FDA's review of a new antidiabetic therapy. N Engl J Med. 2010;362:774–777.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit