Abstract
Diabetes mellitus and cancer are two growing health problems. They have in common many modifiable risk factors including sex, age, obesity, physical activity, diet, alcohol, and smoking, and have a long latency before overtly manifesting. Patients with diabetes experience a roughly 20–25% higher cancer incidence compared to individuals without diabetes, and it depends on cancer site. Moreover, patients with diabetes who further develop cancer have increased early and late mortality in comparison with cancer patients without diabetes. Prediabetes and metabolic syndrome are also related to an increased risk of developing and die from cancer. Possible mechanisms linking diabetes and prediabetes with cancer include hyperglycemia (endogenous or exogenous), hyperinsulinemia, and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormone metabolism, and adipokines. It becomes crucial to define the right orientation of the associations between diabetes and cancer in order to identify the modifiable pathogenic mechanisms. The common soil hypothesis claims that prediabetes and diabetes, as well as metabolic syndrome, may be considered a surrogate sign for dietary risk factors of cancer. The clepsydra of foods may help choose foods associated with healthy benefit while avoiding foods associated with harm, including cancer.
Similar content being viewed by others
References
International Diabetes Federation. IDF Diabetes, 7 ed. Brussels, Belgium: International Diabetes Federation, (2015). http://www.diabetesatlas.org
World Health Organization (WHO), International Agency for Research on Cancer (IARC)—GLOBOCAN 2012 and Cancer fact sheets
World Health Organization (WHO), Cancer fact sheet N° 97 Updated February 2015
E.W. Gregg, X. Zhuo, Y.J. Cheng, A.L. Albright, K.M. Narayan, T.J. Thompson, Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985-2011: a modeling study. Lancet Diabetes Endocrinol. 2, 867–874 (2014)
P. Vineis, C.P. Wild, Global cancer patterns: causes and prevention. Lancet 383, 549–557 (2014)
M. Arnold, N. Pandeya, G. Byrnes et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 16, 36–46 (2015)
S.A. Tanumihardjo, C. Anderson, M. Kaufer-Horwitz et al. Poverty, obesity, and malnutrition: an international perspective recognizing the paradox. J. Am. Diet. Assoc. 107, 1966–1972 (2007)
E. Giovannucci, D.M. Harlan, M.C. Archer et al. Diabetes and cancer: a consensus report. Diabetes Care 33, 1674–1685 (2010)
WHO. Global status report on non-communicable diseases 2014. pp 1–141. http://www.who.int/chp/ncd_global_status_report/en/
K. Esposito, F. Ciardiello, D. Giugliano, Unhealthy diets: a common soil for the association of metabolic syndrome and cancer. Endocrine 46, 39–42 (2014)
K. Ranc, M.E. Jørgensen, S. Friis, B. Carstensen, Mortality after cancer among patients with diabetes mellitus: effect of diabetes duration and treatment. Diabetologia 57(5), 927–934 (2014)
A. Renehan, U. Smith, M.S. Kirkman, Linking diabetes and cancer: a consensus on complexity. Lancet 375(9733), 2201–2 (2010).
S.M. Bluethmann, A.B. Mariotto, J.H. Rowland, Anticipating the “Silver Tsunami”: prevalence trajectories and comorbidity burden among older cancer survivors in the United States. Cancer Epidemiol. Biomarkers Prev. 25(7), 1029–1036 (2016)
E.C. de Haas, S.F. Oosting, J.D. Lefrandt et al. The metabolic syndrome in cancer survivors. Lancet Oncol. 11, 193–203 (2010)
A.J. Redig, H.G. Munshi, Care of the cancer survivor: metabolic syndrome after hormone-modifying therapy. Am. J. Med. 123, 87 (2010). e1–87.e6
S.C. Darby, M. Ewertz, P. McGale et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N. Engl. J. Med. 368, 987–998 (2013)
T. Tuffier, Diabete et neoplasmes. Arch. Gen. de Med. 7, 129–140 (1988)
Y. Shi, F.B. Hu, The global implications of diabetes and cancer. Lancet 383(9933), 1947–1948 (2014). 7
I.C. Lega, A.S. Wilton, P.C. Austin et al. The temporal relationship between diabetes and cancer. Cancer. 17, 2731–2738 (2016)
Y. Handelsman, D. Leroith, Z.T. Bloomgarden et al. Diabetes and cancer—an AACE/ACE consensus statement. Endocr. Pract. 19(4), 675–693 (2013)
A. Satija, D. Spiegelman, E. Giovannucci, F.B. Hu, Type 2 diabetes and risk of cancer. BMJ 2, 350 (2015). g7707
C. De Nunzio, A. Tubaro, Prostate cancer: diabetes and prostate cancer - an open debate. Nat. Rev. Urol. 10, 12–14 (2013)
D. Bansal, A. Bhansali, G. Kapil, K. Undela, P. Tiwari, Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 16, 151–158 (2013). S1
K.K. Tsilidis, N.E. Allen, P.N. Appleby et al. Diabetes mellitus and risk of prostate cancer in the European prospective investigation into cancer and nutrition. Int. J. Cancer 136, 372–381 (2015)
C.H. Tseng, Diabetes and risk of prostate cancer: a study using the National Health Insurance. Diabetes Care 34, 616–621 (2011)
Q. Li, S. Kuriyama, M. Kakizaki et al. History of diabetes mellitus and the risk of prostate cancer: the Ohsaki cohort study. Cancer Causes Control 21, 1025–1032 (2010)
L. Bensimon, H. Yin, S. Suissa, M.N. Pollak, L. Azoulay, Type 2 diabetes and the risk of mortality among patients with prostate cancer. Cancer Causes Control 25, 329–338 (2014)
S.R. Seshasai, S. Kaptoge, A. Thompson et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 364, 829–841 (2011)
R. Dankner, P. Boffetta, R.D. Balicer et al. Time-dependent risk of cancer after a diabetes diagnosis in a cohort of 2.3 million adults. Am. J. Epidemiol. 183(12), 1098–1106 (2016). 15
K.K. Tsilidis, J.C. Kasimis, D.S. Lopez, Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 2, 350 (2015). g7607
A.G. Tabak, M. Jokela, T.N. Akbaraly et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373, 2215–2221 (2009)
E. Giovannucci, D. Michaud, The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 132, 2208–2225 (2007)
J.A. Johnson, S.L. Bowker, Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia 54, 25–31 (2011)
B.B. Barone, H.C. Yeh, C.F. Snyder et al. Postoperative mortality in cancer patients with preexisting diabetes: systematic review and meta-analysis. Diabetes Care 33, 931–939 (2010)
B.B. Barone, H.C. Yeh, C.F. Snyder et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 300, 2754–2764 (2008)
A.G. Renehan, H.C. Yeh, J.A. Johnson et al. Diabetes and cancer evaluating the impact of diabetes on mortality in patients with cancer. Diabetologia 55, 1619–1632 (2012)
J.M. Baena-Díez, J. Peñafiel, I. Subirana et al. Risk of cause-specific death in individuals with diabetes: a competing risks analysis. Diabetes Care. 11, 1987–1995 (2016)
M. Tancredi, A. Rosengren, A.M. Svensson et al. Excess mortality among persons with type 2 diabetes. N. Engl. J. Med. 373, 1720–1732 (2015)
A. Rawshani, A.M. Svensson, B. Zethelius et al. Association between socioeconomic status and mortality, cardiovascular disease, and cancer in patients with type 2 diabetes. JAMA Intern. Med. 176(8), 1146–1154 (2016). 1
B. Carstensen, S.H. Read, S. Friis et al. Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals. Diabetologia 59(5), 980–988 (2016)
A. Guilherme, J.V. Virbasius, V. Puri, M.P. Czech, Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell. Biol. 9, 367–377 (2008)
I.J. Neeland, A.T. Turer, C.L. Ayers et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 308, 1150–1159 (2012)
K. Bhaskaran, I. Douglas, H. Forbes et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet 384(9945), 755–765 (2014). 30
K.G.M.M. Alberti, R.H. Eckel, S.M. Grundy et al. International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009)
X. Yang, G.T.C. Ko, W.Y. So et al. Associations of hyperglycemia and insulin usage with the risk of cancer in type 2 diabetes: the Hong Kong Diabetes Registry. Diabetes 59, 1254–1260 (2010)
J.C. de Beer, L. Liebenberg, Does cancer risk increase with HbA1c, independent of diabetes? Br. J. Cancer 110(9), 2361–8 (2014). 29
C. Hope, A. Robertshaw, K.L. Cheung et al. Relationship between HbA1c and cancer in people with or without diabetes: a systematic review. Diabet. Med. 8, 1013–1025 (2016)
R. Vigneri, I.D. Goldfine, L. Frittitta, Insulin, insulin receptors, and cancer. J. Endocrinol. Invest. 12, 1365–1376 (2016)
NCD Risk Factor Collaboration (NCD-RisC), Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 1377–1396 (2016)
B. Lauby-Secretan, C. Scoccianti, D. Loomis et al. Body Fatness and Cancer—Viewpoint of the IARC Working Group. N. Engl. J. Med. 375(8), 794–798 (2016). 25
P.T. Campbell, Obesity: a certain and avoidable cause of cancer. Lancet 384(9945), 727–8 (2014). 30
M. Arnold, M. Leitzmann, H. Freisling et al. Obesity and cancer: an update of the global impact. Cancer Epidemiol. 41, 8–15 (2016)
International Agency for Research on Cancer. IARC handbooks of cancer prevention: weight control and physical activity. (IARC Press, Lyon), (2002). Vol. 6
A.G. Renehan, M. Tyson, M. Egger et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569–78 (2008)
N.M. Iyengar, C.A. Hudis, A.J. Dannenberg, Obesity and cancer: local and systemic mechanisms. Annu. Rev. Med. 66, 297–309 (2015)
S.D. Hursting, J. Digiovanni, A.J. Dannenberg et al. Obesity, energy balance, and cancer: new opportunities for prevention. Cancer Prev. Res. 5, 1260–1272 (2012)
N. Parekh, Y. Lin, R.B. Hayes et al. Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey. Cancer Causes Control 21(4), 631–642 (2010)
M.N. Pollak, E.S. Schernhammer, S.E. Hankinson, Insulin-like growth factors and neoplasia. Nat. Rev. Cancer 4, 505–518 (2004)
K.K. Wong, J.A. Engelman, L.C. Cantley, Targeting the PI3K signaling pathway in cancer. Curr. Opin. Genet. Dev. 20, 87–90 (2010)
R. Zoncu, A. Efeyan, D.M. Sabatini, mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12, 21–35 (2011)
E. Barrett-Connor, K.T. Khaw, S.S. Yen, Endogenous sex hormone levels in older adult men with diabetes mellitus. Am. J. Epidemiol. 132, 895–901 (1990)
D. Housa, J. Housova, Z. Vernerova, M. Haluzik, Adipocytokines and cancer. Physiol. Res. 55, 233–244 (2006)
A. Mantovani, P. Allavena, A. Sica, F. Balkwill, Cancer-related inflammation. Nature 454, 436–444 (2008)
Y. Huang, X. Cai, M. Qiu et al. Prediabetes and the risk of cancer: a meta-analysis. Diabetologia 57, 2261–2269 (2014)
R.A. DeFronzo, M. Abdul-Ghani, Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose. Am. J. Cardiol. 108, 3B–24B (2011)
M. Buysschaert, J.L. Medina, M. Bergman, A. Shah, J. Lonier, Prediabetes and associated disorders. Endocrine 48(2), 371–393 (2015)
O. Tabak, R. Gelisgen, H. Erman et al. Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus. Clin. Invest. Med. 34, E163–E171 (2011)
C.S. Pereira, P. Molz, R.P. Palazzo et al. DNA damage and cytotoxicity in adult subjects with prediabetes. Mutat. Res. 753, 76–81 (2013)
M.G. Vander Heiden, L.C. Cantley, C.B. Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009)
P. Stattin, O. Björ, P. Ferrari et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care 30, 561–567 (2007)
M. Iwatsuki, K. Mimori, T. Yokobori et al. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 101, 293–299 (2010)
X.H. Zhou, Q. Qiao, B. Zethelius et al. Diabetes, prediabetes and cancer mortality. Diabetologia 53, 1867–1876 (2010)
S. Gao, A. Li, F. Liu et al. NCOA5 haploinsufficiency results in glucose intolerance and subsequent hepatocellular carcinoma. Cancer Cell 24, 725–737 (2013)
D. Giugliano, M.I. Maiorino, K. Esposito, Linking prediabetes and cancer: a complex issue. Diabetologia 58(1), 201–202 (2015)
K.-H. Wagner, H. Brath, A global view on the development of non communicable diseases. Prev. Med. 54(suppl), S38–S41 (2012)
M. Aguilar, T. Bhuket, S. Torres et al. Prevalence of the metabolic syndrome in the United States, 2003–2012. JAMA 313(19), 1973–1974 (2015). 19
K. Esposito, A. Capuano, D. Giugliano, Metabolic syndrome and cancer: holistic or reductionist? Endocrine 45(3), 362–364 (2014)
K. Esposito, P. Chiodini, A. Capuano et al. Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis. Menopause 20(12), 1301–1309 (2013)
K. Esposito, P. Chiodini, A. Capuano et al. Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine 45(1), 28–36 (2014)
J.R. Jaggers, X. Sui, S.P. Hooker, M.J. LaMonte et al. Metabolic syndrome and risk of cancer mortality in men. Eur. J. Cancer 45, 1831–1838 (2009)
J.R. Zhou, G.L. Blackburn, W.A. Walker, Symposium introduction: metabolic syndrome and the onset of cancer. Am. J. Clin. Nutr. 86, s817–s819 (2007)
K. Esposito, P. Chiodini, A. Colao et al. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 35, 2402–2411 (2012)
J.L. Harding, M. Sooriyakumaran, K.J. Anstey et al. Hypertension, antihypertensive treatment and cancer incidence and mortality: a pooled collaborative analysis of 12 Australian and New Zealand cohorts. J. Hypertens. 34(1), 149–155 (2016)
W.H. Chow, G. Gridley, J.F. Fraumani Jr, B. Jarvholm, Obesity, hypertension, and the risk of kidney cancer in men. N. Engl. J. Med. 343, 1305–1311 (2000)
N.J. Kocher, C. Rjepaj, H. Robyak et al. Hypertension is the primary component of metabolic syndrome associated with pathologic features of kidney cancer. World J. Urol. (2016). doi:10.1007/s00345-016-1850-2
N. Hayashi, M. Matsushima, T. Yamamoto et al. The impact of hypertriglyceridemia on prostate cancer development in patients aged ≥60 years. BJU Int. 109(4), 515–519 (2012)
H. Jafri, A.A. Alsheikh-Ali, R.H. Karas, Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipidaltering therapy. J. Am. Coll. Cardiol. 55, 2846–2854 (2010)
M. Ezzati, E. Riboli, Behavioral and dietary risk factors for noncommunicable diseases. N. Engl. J. Med. 369, 954–964 (2013)
W.E. Hardman, Diet components can suppress inflammation and reduce cancer risk. Nutr. Res. Pract. 8(3), 233–240 (2014)
C. Micucci, D. Valli, G. Matacchione, A. Catalano, Current perspectives between metabolic syndrome and cancer. Oncotarget. 25, 38959–38972 (2016)
P.C. Calder, N. Ahluwalia, F. Brouns et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br. J. Nutr. 106(Suppl 3), S5–78 (2011)
S.I. Grivennikov, F.R. Greten, N. Karin, Immunity, inflammation, and cancer. Cell 140, 883–899 (2010)
F.E. Deng, N. Shivappa, Y. Tang et al. Association between diet-related inflammation, all-cause, all-cancer, and cardiovascular disease mortality, with special focus on prediabetics: findings from NHANES III. Eur. J. Nutr. (2016). doi:10.1007/s00394-016-1158-4
American Cancer Society. Cancer Facts and Figures 2012. (American Cancer Society, Atlanta, GA), (2012)
R. Doll, R. Peto, The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66, 1191–1308 (1981)
K. Esposito, D. Giugliano, Healthy lifestyle for metabolic health: no more excuse! Endocrine 46(2), 176–178 (2014)
P.C. Hallal, L.B. Andersen, F.C. Bull, R. Guthold, W. Haskell, U. Ekelund, Lancet Physical Activity Series Working Group, Global physical activity levels: surveillance progress, pitfalls, and prospects. Lancet 380(9838), 247–257 (2012)
S.C. Moore, I.M. Lee, E. Weiderpass et al. Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern. Med. 176(6), 816–825 (2016). 1
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approvement
This article does not contain any studies with human participants performed by any of the authors.
Rights and permissions
About this article
Cite this article
Scappaticcio, L., Maiorino, M.I., Bellastella, G. et al. Insights into the relationships between diabetes, prediabetes, and cancer. Endocrine 56, 231–239 (2017). https://doi.org/10.1007/s12020-016-1216-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-016-1216-y