Insulin analogues and cancer risk: cause for concern or cause célèbre?
People with diabetes, particularly those with type 2 diabetes, may be at an increased risk of cancer. Furthermore, their cancer risk may be modified by treatment choices. In this respect, metformin may be protective, whereas insulin and insulin analogues can function as growth factors and therefore have theoretical potential to promote tumour proliferation. Analogues causing inappropriate prolonged stimulation of the insulin receptor, or excess stimulation of the IGF-1 receptor, are the most likely to show mitogenic properties in laboratory studies. Some recent epidemiological studies appear to be consistent with these experimental findings, suggesting that there could be different relative risks for cancer associated with different insulins, although these studies have attracted some methodological criticism. However, it is biologically plausible that hormonal factors that influence neoplasia could begin to manifest their effects in surprisingly short timescales (within 2 years) and hence these epidemiological studies justify further research. Even if future research were to document an increase in cancer risk among insulin users, this would be unlikely to significantly diminish the favourable benefit-risk ratio for patients requiring insulin therapy. There is a need for further population studies and for the development of new laboratory models that are more sophisticated than previous experimental methods employed to assess potential tumour growth-promoting properties of insulins.
Pollak
M
M
Department of Medicine, McGill University, Montreal, Canada. michael.pollak@mcgill.ca <michael.pollak@mcgill.ca>
Russell-Jones
D
D
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects* / Q000031:analogs & derivatives; D009369:Neoplasms / Q000139:chemically induced*; D011446:Prospective Studies; D017526:Receptor, IGF Type 1 / Q000502:physiology; D012307:Risk Factors
D007004:Hypoglycemic Agents; D007328:Insulin; D017526:Receptor, IGF Type 1