From obesity to diabetes and cancer: epidemiological links and role of therapies

Abstract

Increasing evidence suggests a complex relationship between obesity, diabetes and cancer. Here we review the evidence for the association between obesity and diabetes and a wide range of cancer types. In many cases the evidence for a positive association is strong, but for other cancer types a more complex picture emerges with some site-specific cancers associated with obesity but not to diabetes, and some associated with type I but not type II diabetes. The evidence therefore suggests the existence of cumulative common and differential mechanisms influencing the relationship between these diseases. Importantly, we highlight the influence of antidiabetics on cancer and antineoplastic agents on diabetes and in particular that antineoplastic targeting of insulin/IGF-1 signalling induces hyperglycaemia that often evolves to overt diabetes. Overall, a coincidence of diabetes and cancer worsens outcome and increases mortality. Future epidemiology should consider dose and time of exposure to both disease and treatment, and should classify cancers by their molecular signatures. Well-controlled studies on the development of diabetes upon cancer treatment are necessary and should identify the underlying mechanisms responsible for these reciprocal interactions. Given the global epidemic of diabetes, preventing both cancer occurrence in diabetics and the onset of diabetes in cancer patients will translate into a substantial socioeconomic benefit.

Figure 1

Association of cancers (classified by site) with obesity, diabetes and treatments. Raw data for this figure are presented in Supplementary Tables S1 and S2. Cancer relative risk was directly – red colours – or inversely (protection) – green colours – associated with obesity (Ob), TIID, TID or ADTs: insulin (Ins) and sulphonylurea (SU) that increase circulating insulin and metformin (Met) and TZDs that decrease blood glucose. Not statistically significant (NS) association (blue squares). Squares with very light red or green shadow represent trends to direct (red shadow) or inverse (green shadow) association, although statistically not significant mainly because of lack of sufficient studies.