Strong Epidemiologic Evidence Links Diabetes and Cancer

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There is strong and consistent epidemiologic evidence that diabetes causes an increased risk of various cancers and cancer mortality, reported Jeffrey A. Johnson, PhD, professor in the Department of Public Health Sciences at the University of Alberta, speaking today at the American Diabetes Association’s 70 Scientific Sessions in Orlando.

The link between diabetes and cancer has been bantered about at length in recent years and for good reason—they’re both complex and heterogenous, both are common in older adults, and both are prevalent, with increasing incidence. But just because two things share common characteristics doesn’t necessarily mean they have a causal relationship. But with two separate cohorts showing that cancer causes the death of almost 30% of type 2 diabetes patients, the second-leading cause of death after cardiovascular disease, Dr. Johnson took a deeper look into the research to see if there was a link between the two conditions.

In his session “Epidemiology of Diabetes and Cancer,” Dr. Johnson referenced 8 systematic studies representing 157 studies total, each of which demonstrated diabetes patients rates of risk for various types of cancer: pancreas (1.82), colorectal (1.30), bladder (1.24), prostate (0.84), liver (2.5), breast (1.20), endometrial (2.1), and nonhodgkins lymphoma (1.41). What he found in these studies was that high blood sugar was related to cancer mortality; as glucose increased so did cancer mortality. The relationship between the two was not confounded by body mass index, which suggests that hyperinsulinemia plays a role.

But not satisfied with only that data, Dr, Johnson performed a meta-analysis of intensive glycemic control and cancer risk. In ACCORD, 2 separate UKPDS studies, and VADT, reducing blood glucose was not shown to affect cancer mortality. When investigating the link between C-peptides and colorectal cancers, there was a four-fold higher risk for colon cancer in those with high C-peptide levels, information backed in a study by Ma and colleagues. A review on diabetes and all-cause mortality revealed at least a 1.51 greater risk for endometrial, breast, and gastric cancers. Another study, by Lipscombe et al, showed that diabetes patients had a 40% increased mortality risk within 5 years of breast cancer diagnosis. The Lipscombe study’s results could be based on the fact that women with diabetes have reduced rates of mammography, a 30% reduction in screening that is independent of age or social factors; diabetes patients are also 40% less likely to receive a pap test for cervical cancer.

Dr. Johnson also presented data showing comparisons between glucose-lowering therapies and cancer risk, with metformin serving as the reference group. For type 2 diabetes patients using sulfonylureas their risk of developing cancer increased 1.3; insulin added 1.9 more risk. Another study Dr. Johnson referenced that also used metformin as the reference group showed that diabetes patients using sulfonylureas had an increased incidence of 1.3, for combination therapy incidence increased by 1.08, and for insulin-based therapies the incidence risk was 1.42.

While some studies conflicted the hypothesis that diabetes and cancer are linked, there was more evidence suggesting that they are related, which is what led Dr. Johnson to conclude that there is strong and consistent epidemiologic evidence of increased risk of various cancers and cancer mortality. According to Dr. Johnson, the epidemiologic evidence suggests multiple possible mechanisms at work in this conclusion; obesity and health behaviors, hyperglycemia, hyperinsulinemia, and “displaced priorities” (like the delaying of screening), are all at work in the relationship between cancer and diabetes.

So while treatments that reduce insulin are associated with reduced cancer risk and vice versa, Dr. Johnson said “we still have many unanswered questions.”