The Relationship Between Diabetes and Cancer

Diabetes increases cancer risk, particularly for certain cancers, yet cancer screenings are performed less on people with diabetes than people without diabetes.

Diabetes mellitus has shown to increase the risk of cancer and mortality rates. Cancer and diabetes share similar risk factors such as age, obesity, smoking. The link between cancer and diabetes is not entirely understood, but biological mechanisms linking diabetes and cancer are hyperglycemia, hyperinsulinemia, increased bioactivity of insulin-like growth factor 1, oxidative stress, dysregulations of sex hormones, and chronic inflammation. Some medications used to treat diabetes are being studied to identify a risk of cancer, and some have been theorized to increase or decrease the risk. However, no medications have been linked to specific cancers. Although there is a known risk for cancer for people with diabetes, routine checks are still absent, and the potential of early detection and treatment of cancer is missed. This article wanted to highlight the need for cancer screenings in patients with diabetes.

A meta-analysis studying the association between diabetes and developing cancer showed a 10% increase in the relative risk (RR, 1.10; 95% CI, 1.04 to 1.17) to develop cancer. Diseases that occurred more frequently included hepatocellular, hepatobiliary, pancreas, breast, ovarian, endometrial, and gastrointestinal cancers. Since age is a risk for cancer, type 2 diabetes has a higher association than type 1 in the development of cancer.

The association between mortality rates and people who have diabetes and develop cancer is not clear. We would expect the mortality rates of anyone with either cancer or diabetes to be higher than the average person, so having both diseases at once would undoubtedly increase the risk of death. People with diabetes have less aggressive cancer treatment and worse outcomes compared to people with cancer without diabetes. By making more connections between certain cancers and diabetes, specific screenings can become routine with a diabetes diagnosis.

Since diabetes is increasing in incidence worldwide, cancer rates can be expected to increase, unfortunately. Identifying risk factors for both and treating or avoiding them early is the best way to reduce the incidences of both diseases. As mentioned earlier, age, obesity, smoking, and physical inactivity are risk factors for both diabetes mellitus and cancer. However, biological factors play an essential role in the formation of both diseases. Cell proliferation and apoptosis pathways may be shared for both disorders. High levels of insulin and glucose can fuel neoplastic cancer formation and cancer progression. It’s been hypothesized that insulin resistance, hyperinsulinemia, and hyperglycemia link T2DM and pancreatic cancer. Hyperinsulinemia also increases estrogen and androgen levels and decreases sex hormones binding globulin. Hyperglycemia causes oxidative stress and DNA damage. A link between colorectal cancer and T2DM has the most robust pathophysiological evidence. T2DM creates a microenvironment that can alter microbiota and cause chronic local inflammation.

Medications used to treat diabetes have been thought to increase or decrease the incidence of cancer. Several studies have been made to monitor cancer incidences in patients with diabetes. Conflicting results indicate the need for more studies that have more power. Since no specific diabetic therapy has a risk for cancer, cancer risk should not be in consideration when deciding on a treatment for an average patient. More recently, SGLT-2 inhibitors have been implicated in increasing the risk for cancer but a meta-analysis and the relatively new introduction of this medication to clinical practice disproved this theory. Other therapies used to treat diabetes that have been theorized to increase the risk of cancer are incretin-based drugs such as GLP-1 agonists and DPP-4 inhibitors, thiazolidinediones, sulfonylureas, metformin, and insulin analogs. No evidence links these medications to cancer.

Having diabetes increases cancer risk in patients, compared to people who do not have diabetes. Still, cancer screenings for people with diabetes are less than for a person without. Older aged persons who develop type-1 diabetes should be screened for pancreatic cancer since this form of cancer is deadly and is almost always detected late. No correlations could be made between diabetic medications and cancer development. Identifying patients who have risk factors and treating them early are the best ways to prevent either disease. More studies need to be conducted to identify risk factors and pathogenic mechanisms which lead to cancer development in patients with diabetes.

Practice Pearls:

• Patients with diabetes and risk factors for cancer development should be screened routinely.
• Medications that treat diabetes are not associated with cancer development.
• Early detection of both diabetes and cancer would lead to better outcomes.

Suh, Sunghwan, and Kwang Won Kim. “Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment.” Diabetes & metabolism journal, vol. 43,6 (2019): 733-743. doi:10.4093/dmj.2019.0177

Antonio Bess, Pharm D Candidate, Florida Agricultural & Mechanical University School of Pharmacy

See more about how diabetes increases cancer risk in our Oncology center.