Insulin therapy and risk of colorectal cancer: an updated meta-analysis of epidemiological studies

Objective: An increasing number of studies show that exogenous insulin therapy may promote colorectal carcinogenesis. However, the results of the association between insulin therapy and risk of colorectal cancer (CRC) among type 2 diabetes patients are inconsistent. The purpose of our study is to examine the effect of insulin therapy on CRC risk among patients with type 2 diabetes in an updated meta-analysis. Research design and methods: Medline and Embase were searched for the reference lists of pertinent articles published from January 1970 to April 2013. Two investigators independently extracted the data and reached consensus on the inclusion and exclusion criteria. Pooled relative risks and 95% confidence intervals were calculated with a random-effects model. Results: Analysis of six studies, including 374,950 participants, showed that compared with non-insulin or metformin treatment, insulin treatment was associated with an increase of 37% in the risk of colorectal neoplasm among patients with type 2 diabetes, with moderate heterogeneity (I-2 = 40%). The sensitivity analysis showed that exclusion of one small case-control study had no appreciable changes on the pooled results. Subgroup analyses suggested that there were significant positive associations between insulin therapy and risk of CRC in some subgroups, rather than all subgroups. Conclusions: Our meta-analysis supports a relationship between insulin therapy and increased risk of CRC in patients with type 2 diabetes. Because of bias and confounding of included studies, caution is needed when interpreting our results. Further investigations are needed.