Diabetes, insulin, insulin analogues, and cancer

Numerous epidemiological studies have demonstrated an association between increased risk of cancer development and progression and type 2 diabetes mellitus as well as obesity. The underlying mechanisms remain elusive, but hyperinsulinaemia in the presence of insulin resistance appears to be an important factor. Hyperinsulinaemia may favour tumorigenesis, as insulin has not only metabolic actions, but is also mitogenic at high concentrations. Besides, susceptibility of tumour cells against insulin may be increased due to changes in the insulin receptor profile. A diabetes therapy with insulin or sulfonylureas, which leads to elevated exogenous or endogenous insulin levels, appears to be related with an increased cancer risk, whereas administration of metformin or thiazolidinediones, which is associated with a decrease of insulin concentrations, results in risk reduction. However, in light of the numerous epidemiological studies showing an association between increased cancer risk and reduced physical activity one cannot exclude that hyperinsulinaemia in the presence of insulin resistance is only a surrogate parameter of reduced physical activity. In the past years, several insulin analogues have been developed which may have altered mitogenic actions compared to human insulin due to their structural changes. For the long-acting analogue insulin glargine, in vitro data, though controversial, pointed to an increased mitogenicity that was, however, not confirmed by in vivo studies. Recently, six clinical studies have been published that analysed the association between the application of insulin glargine (Lantus) and cancer development. The current clinical data do not allow the conclusion that treatment with insulin glargine is associated with increased cancer risk. On the other hand, prospective studies that exclude an impact on cancer risk in risk populations are currently not available. Future studies are required to investigate whether a subpopulation characterised by a less rapid metabolization of insulin glargine in vivo may be at increased cancer risk. In the present article, we give an overview on the association between diabetes mellitus, its treatment with insulin analogues, and cancer. © Georg Thieme Verlag KG Stuttgart.