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?

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To give an overview on the relationship between diabetes mellitus and increased cancer risk. We identified studies evaluating the association between diabetes mellitus, its treatment with insulin and insulin analogues and malignancies, paying special attention to studies on in vitro and in vivo effects of the long-acting analogue insulin glargine. Even although the pathophysiological mechanisms underlying the relationship between elevated cancer risk and Type 2 diabetes mellitus are not completely understood, hyperinsulinaemia in the presence of insulin resistance appears to be a key factor. Because of the mitogenic actions of insulin at high concentrations, hyperinsulinaemia may favour tumorigenesis. In line with this, an insulin-based therapy is associated with an increased cancer risk, whereas an insulin-sensitizing treatment results in a cancer risk reduction. Furthermore, alterations of the insulin receptor profile on tumour cells may contribute to an enhanced susceptibility towards insulin. Studies on the analogue insulin glargine have been controversial. In vitro data pointed to an elevated mitogenicity of insulin glargine, whereas in vivo data did not confirm cancerogenous effects. Moreover, recently published clinical studies on the association of insulin glargine (Lantus®) and cancer suggest that treatment with insulin glargine is not associated with increased cancer risk. The relationship between elevated cancer risk and Type 2 diabetes mellitus has been shown by numerous epidemiological studies, with endogenous and exogenous hyperinsulinaemia in the presence of insulin resistance as potential underlying pathophysiological mechanisms. Recent clinical studies do not support an increased cancer risk in patients treated with insulin glargine.