Diabetes and cancer are prevalent diseases that have a large global impact on health and healthcare resources. Epidemiological studies suggest that patients with diabetes are at a higher risk of developing certain types of cancers. This may be due to diabetes and cancer sharing common risk factors, but it is likely that any association is intricately linked by biological mechanisms, which are only starting to be unravelled. This is further complicated by emerging data that suggest that some diabetes therapies may predispose or promote development of certain cancers, while metformin appears to have anti-neoplastic effects. This review considers the evidence associating diabetes, diabetes therapies and cancer.
VigneriPFrascaFSciaccaL. Diabetes and cancer. Endocr Relat Cancer2009;16:1103–23.
3.
BaroneBBYehHCSnyderCF. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA2008;300:2754-64.
4.
LipscombeLLGoodwinPJZinmanB. The impact of diabetes on survival following breast cancer. Breast Cancer Res Treat2008;109:389-95.
5.
MaJLiHGiovannucciE. Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis. Lancet Oncol2008;9:1039-47.
6.
MardilovichKPankratzSLShawLM. Expression and function of the insulin receptor substrate proteins in cancer. Cell Commun Signal2009;7:14.
7.
PollakM. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer2008;8:915-28.
8.
YunJRagoCCheongI. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science2009;325:1555–59.
9.
SimonsALMattsonDMDornfieldK. Glucose-deprivation induced metabolic oxidative stress and cancer therapy. J Cancer Res Ther2009;5:Suppl 1:S2-6.
10.
PollakM. Do cancer cells care if their host is hungry?Cell Metab2009;9:401–3.
11.
BarclayAWPetoczPMcMillan-PriceJ. Glycemic index, glycemic load, and chronic disease risk – a meta-analysis of observational studies. Am J Clin Nutr2008;87:627–37.
12.
KurtzhalsPSchafferLSorensenA. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes2000;49:999–1005.
13.
KesslerII. Cancer mortality among diabetics. J Natl Cancer Inst1970;44:673–86.
14.
JorgensenLNDideriksenLHDrejerK. Carcinogenic effect of the human insulin analogue B10Asp in female rats. Diabetologia1992;35:Suppl.1:A3.
15.
HemkensLGGrouvenUBenderR. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia2009;52:1732–44.
16.
CurrieCJPooleCDGaleEA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia2009;52:1766–77.
17.
ColhounHM. SDRN Epidemiology Group. Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia2009;52:1755–65.
18.
JonassonJMLjungRTalbδckM. Insulin glargine use and short-term incidence of malignancies – a population-based follow-up study in Sweden. Diabetologia2009;52:1745–54.
19.
DejgaardALynggaardHRǾstamJ. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia2009;52:2507–12.
20.
EvansJMDonnellyLAEmslie-SmithAM. Metformin and reduced risk of cancer in diabetic patients. BMJ2005;330:1304-5.
21.
BowkerSLMajumdarSRVeugelersP. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care2006;29:254-8.
22.
JiralerspongSPallaSLGiordanoSH. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol2009;27:3297-302.
23.
PatelTHrubyGBadaniK. Clinical outcomes after radical prostatectomy in diabetic patients treated with metformin. Urology2010;76:1240-44.
24.
HosonoKEndoHTakahashiH. ‘Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial.’ Cancer Prev Res (Phila)2010;3:1077-83.
25.
HadadSMDewarJAElseedawyE. Gene Signature of metformin actions on primary breast cancer within a window of opportunity randomized clinical trial. J Clin Oncol2010;28(Suppl):560.
26.
Ben SahraILaurentKLoubatA. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene2008;27:3576-86.
27.
AimarettiG. Liraglutide: a once daily human glucagon-like peptide-1 analogue. J Endocrinol Invest2009;32:701–3.
28.
WolfILigumskyHKaufmanB. Glucagon-like peptide (GLP)-1 and the synthetic analogue exenatide: From novel therapy for diabetes to growth inhibition of breast cancer cells. J Clin Oncol2010:(suppl; abstr e21035).
29.
MatveyenkoAVDrySCoxHI. Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes2009;28:1604–15.
30.
PiccinniCMotolaDMarchesiniG. Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting. Diabetes Care2011;doi 10.2337/dc10241210.2337/dc102412.
