Unfolding link between diabetes and cancer

A growing body of evidence has shown that type 2 diabetes is associated with an increased risk of total cancer death and total cancer incidence, including cancers of the liver, endometrium, pancreas, kidney, colorectal, bladder and breast. Of interest, the risk of prostate cancer is significantly decreased. Although the majority of the studies on this topic have been carried out in Western countries, those risk ratios of all-cancer mortality and incidence across all cancer types are reportedly even higher in Asians (Table 1). Type 2 diabetes is characterized by hyperglycemia secondary to insulin resistance, and compensatory hyperinsulinemia. There are several putative mechanisms involving these factors to account for the higher risk of cancer in diabetes. In addition, it has been shown that hyperglycemia promotes cancer emergence and metastasis. However, high-quality evidence scrutinizing the link between glycemic control and the risk of cancer is scarce. More evidence has been accumulating with regard to potential oncogenic effects of diabetes treatment. Of note, it was speculated for a certain period of time that insulin formulation might increase the risk of cancer. Current evidence on the risk of cancer in association with any diabetes treatment to prove the causal relationship between those medications and cancer is limited because of their inadequate adjustment for confounders, not accounting for the degree of exposure to drugs and their short follow-up periods. Chen et al. recently carried out pooled analyses of 19 prospective population-based cohorts consisting of data from more than 771,297 Asians, and found that diabetes was significantly associated with an elevated risk of death from overall cancer (hazard ratio 1.26, 95% confidence interval 1.21–1.31). They also reported significant positive associations between diabetes and the risk of mortality from cancers of the endometrium, liver, thyroid, kidney, breast, ovary, pancreas, bile duct, prostate, colorectum, lymphoma, and gallbladder. Although the relative risk is consistent with that in a previous meta-analysis, the strengths of their study design included a huge number of samples with an adequately long follow-up period, an ability to analyze population subgroups and reduced publication biases. Their findings are clinically meaningful in that they point to the urgent implementation of appropriate cancer screening among diabetes patients, and a greater emphasis on therapeutic lifestyle changes in relation to cancer mortality in Asians with diabetes who have been assumed to be relatively insulin deficient. Although their findings are compelling, observational studies should be interpreted with caution, because only a minority of associations between diabetes