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Type 2 diabetes mellitus is associated with an increased risk of cancer
Last reviewed: 02.07.2025
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Type 2 diabetes increases the risk of developing many diseases, including various types of cancer; however, the mechanisms responsible for this association remain unclear.
A recent study published in the journal BMC Medicine looks at the risk of cancer in diabetics.
Type 2 diabetes is a metabolic disease caused by both genetic and environmental factors. Large epidemiological studies have shown that people with diabetes have a higher risk of developing cancers of the liver, pancreas, uterus, colon and rectum, breast, and bladder.
Diabetes is associated with microvascular disease, the most common manifestation of which is diabetic retinopathy (DR), which is the leading cause of vision loss in middle age. Multiple factors, such as high blood sugar, high levels of toxic glycation end products, and activation of several pathways common to cancer, contribute to the development of diabetic retinopathy.
Common phenomena such as oxidative stress, inflammation, vascular abnormalities, and new blood vessel formation are common to both cancer and DR. Thus, better glycemic control may reduce the incidence of cancer in this population.
Overall cancer incidence increased by 20% in patients with diabetes, with the greatest increase in risk for liver and pancreatic cancers, followed by cancers of the oral cavity, gallbladder, female reproductive system, kidney, and brain. This increase in risk ranged from 25 to 34%, with the exception of kidney cancer, where the risk was 44% higher.
Other cancers that modestly increased risk by 17-20% included stomach, skin and breast cancer in women, and urinary tract cancer. The only cancer that decreased in the diabetes cohort was esophageal cancer.
In men with diabetes, the risk of cancer increased by 20%. Patients with concomitant hypertension had a 10% higher risk of cancer, while patients with high blood lipid levels had a 14% lower risk of overall cancer, but an increased risk of breast cancer in women.
An inverse association between hyperlipidemia and cancer may be due to an increased risk of early cardiovascular mortality; however, a direct anticancer effect of high cholesterol levels is also possible.
Patients with diabetes and diabetic retinopathy had a significantly higher overall cancer incidence compared with the cohort without diabetic retinopathy - 32% and 20%, respectively. The incidence of liver, mesothelial, urinary tract and soft tissue cancers was increased in the diabetes with diabetic retinopathy group.
Other sites with a moderately increased risk of cancer included the oral cavity, lip, stomach, colon, and pancreas. Lymphatic system and bone marrow cancers were also more common among patients with diabetes and diabetic retinopathy.
Among patients with diabetic retinopathy, the risk was 13% higher in those with proliferative diabetic retinopathy (PDR) than in those with non-proliferative diabetic retinopathy (NPDR). Stomach, liver, gynecologic, and urinary tract cancers were more common in patients with PDR than in those with NPDR. Similarly, the risk was 25% higher in men than in women.
Diabetes is an independent and significant risk factor for cancer in general and for cancer in certain sites. This risk is increased in people with diabetes who develop diabetic retinopathy, which may be related to significantly higher levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in these patients compared with people with diabetes without diabetic retinopathy.
Systemic inflammation, which is often a response to diabetes, may also increase the risk of various cancers, including liver, pancreatic, colon, and breast cancer. In addition, numerous inflammatory mediators, including proinflammatory cytokines and chemokines, are released in diabetic retinopathy, which may also contribute to carcinogenesis.
These results raise the possibility that diabetes and diabetic retinopathy may share pathogenic features with cancer, and strict blood glucose control to prevent diabetic retinopathy in patients with diabetes may further reduce cancer development.