Primary Care Diabetes
Volume 6, Issue 1 , Pages 1-2, April 2012

Should we consider cancer diagnosis in diabetic patients as a complication of diabetes, or is it iatrogenic sequelae?☆

  • Jaakko Tuomilehto

      Affiliations

    • South Ostrobothnia Central Hospital, Koskenalantie, FIN-60220 Seinäjoki, Finland
    • Danube-University Krems, Center for Vascular Prevention, Dr. Karl-Dorrek Strasse 30, A-3500 Krems, Austria
    • Corresponding Author InformationCorrespondence address: South Ostrobothnia Central Hospital, Koskenalantie, FIN-60220 Seinäjoki, Finland. Tel.: +358 405016316; fax: +358 206108661.

published online 13 February 2012.

Article Outline

 

The risk of cancer is increased in diabetic patients [1], [2] and those with asymptomatic hyperglycaemia [3]. Much of this association is due to high glucose, partially due to the toxic effects of excessive glucose, but hyperglycaemia also offers a pleasant environment for cancer cells that consume much more glucose than normal cells. In animal studies and mechanistic studies it has been shown that hyperinsulinaemia is promoting the growth of cancer cells [2]. In addition it has previously been proposed that the risk of cancer of many forms is increased among people with diabetes treated with certain antidiabetic drugs [4]. On the other hand, results from some studies, but not from all, have suggested that metformin may lower the risk of cancer [5], and today there are tens of studies ongoing to find out whether metformin can help people with cancer. The final judgment of the potential mitogenic effect of some antidiabetic drugs as well as the putative preventive effect of metformin is still open. We must also keep in mind that all drugs must be tested in many ways regarding the cancer potential and pass these tests clearly before they can be taken to the public market. In the supermarket there are many products that are either proven to cause cancer or have never been properly tested for their cancer potential, but people can buy them freely.

In 2009, it was suggested that patients who had used insulin glargine, a long-acting insulin analogue had an increased risk of cancer [6]. The methodology employed in this study has been strongly criticized [7]. Other studies published at the same time failed to confirm the findings [8], [9], [10] although there was a suggestion of breast cancer risk in a Swedish study [8] but not seen any longer in a further follow-up [11]. It is obvious that more attention should be paid on research methodology in such a very complex situation as pharmacotherapy of type 2 diabetes that may be highly variable and many factors may contribute to the selection of drugs used.

When evaluating the safety of drugs used in prospective observational studies and in clinical practice it is necessary to pay attention to exposure time and the dose of the drug of interest. The analysis of Lind and co-workers in this issue of Primary Care Diabetes is a good example of such an attempt in relation to insulin glargine and two cancers: breast in women and prostate in men [12]. With various statistical methods they are trying to tease out exposure time and dose related effects. Their main conclusions are that the average risk of breast and prostate cancer did not differ between the use of insulin glargine and not use. In addition, they found no difference in the risk of these cancers in relation to longer diabetes duration. This study was relatively small, and we need to wait for the results from a very large Northern European Collaborative analysis of insulin glargine use and cancer risk that are expected to be reported to the European Medicines Agency later on this year.

Diabetic patients need treatments that are effective, but obviously the safety aspects must also be kept in mind [13]. Primary care physicians who take care of most of the prescriptions for diabetic patients must receive information that is balanced, reliable and valid. Therefore, the data collected by various registries are very important, because they can provide information that is never possible to obtain by randomized controlled trials that are usually short-term and targeted to selected populations.

Treatment of diabetes aims at prevention premature mortality and complications related to diabetes. Is cancer diagnosed in a diabetic patient a “complication of diabetes”? If hyperglycaemia or hyperinsulinaemia independently increase the risk of certain cancers, the answer is: Yes. If some risk factors such as obesity, smoking, physical inactivity, unhealthy diet increase simultaneously the risk of both diabetes and cancer, there is a likelihood that they act as confounding factors. Already for a long time it has been understood that several chronic non-communicable diseases – type 2 diabetes, certain cancers, cardiovascular disease, dementia, etc. – share many of their risk factors. Thus, the good news is that the primary prevention of any of these diseases will probably also help in preventing others. It would be very important to discuss not only potential problems that may exist with some treatments, but also wide benefits that they may get from empowering themselves for healthier lifestyles.

Back to Article Outline

References 

  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
  2. Műssig K, Staiger H, Kantartzis K, Fritsche A, Kanz L, Häring HU. Type 2 diabetes mellitus and risk of malignancy: is there a strategy to identify a subphenotype of patients with increased susceptibility to endogenous and exogenous hyperinsulinism?. Diabet. Med. 2011;28:276–286
  3. Zhou XH, Qiao Q, Zethelius B, Pyörälä K, Söderberg S, Pajak A, et al. Diabetes, prediabetes and cancer mortality. for the DECODE Study Group Diabetologia. 2010;53:1867–1876
  4. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29:254–258
  5. 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
  6. Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke GW, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. 2009;52:1732–1744
  7. Pocock SJ, Smeeth L. Insulin glargine and malignancy: an unwarranted alarm. Lancet. 2009;374:511–513
  8. Jonasson JM, Ljung R, Talbäck M, Haglund B, Gudbjörnsdòttir 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
  9. Scottish Diabetes Research Network (SDRN) . Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia. 2009;52:1755–1765
  10. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766–2177
  11. Ljung R, Talbäck M, Haglund B, Jonasson JM, Gudbjörnsdòttir S, Steineck G. Insulin glargine use and short-term incidence of malignancies—a three-year population-based observation. Acta Oncol. 2011;50:685–693
  12. Lind M, Fahlén M, Eliasson B, Odén A. The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: an observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes. Primary Care Diabetes. 2012;7:XX–XX
  13. Gough SCL, Belda-Iniesta C, Poole C, Weber M, Russell-Jones D, Falck Hansen B, et al. Insulin therapy in diabetes and cancer risk: current understanding and implications for future study. Adv. Ther. 2011;28(Suppl. 5):1–18

☆ Within two months of publication of these original studies, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency announced that there was no need for any change to the label or prescription practice but suggested that the Marketing Authorisation Holder (MAH) (in this case Sanofi-Aventis as it then was) could organize the collection of new information on this issue.

PII: S1751-9918(12)00016-2

doi:10.1016/j.pcd.2012.01.006

Primary Care Diabetes
Volume 6, Issue 1 , Pages 1-2, April 2012

Article Tools