Diabetes and Cancer: Connections and Clinical Tips

Diabetes and Cancer: Connections and Clinical Tips
Diabetes and Cancer: Connections and Clinical Tips

There is a well-established association between diabetes and cancer. They coexist in the same patient more frequently than would be expected by chance, even adjusting for age and other factors.The most common types of cancer linked to diabetes are solid organ malignancies, including liver, pancreas, colorectal, breast, endometrial, uterine, prostate, and bladder, with liver and pancreas showing the strongest association.2 Diabetes is also an independent risk factor for non-Hodgkin's lymphoma.3 A recent article by Garg et al reviews the cancer-diabetes link.3

Pathophysiology


Pathophysiologic mechanisms underlying the relationship between these two apparently disparate conditions are unclear.3 It has commonly been assumed that diabetes is directly responsible for cancer because of the impact of hyperglycemia. Since cancer cells are glucose-dependent and obtain their energy requirements from fermentation—ie, they perform anaerobic glycolysis in the presence of oxygen—it stands to reason that cancer cells would grow faster in a high-glucose environment.4

RELATED: Endocrine Disorders Resource Center

The Role of Insulin Dysregulation


Current thinking suggests that diabetes serves as a "marker of altered cancer risk," due to changes in underlying metabolic conditions, such as insulin resistance or hyperinsulinemia (either endogenous insulin, due to insulin resistance, or exogenous, due to administered insulin or insulin secretagogues).3 It is theorized that the effects of insulin and hyperinsulinemia on tumor genesis are mediated through the insulin receptor, which is expressed in both normal tissues and tumors.3

Obesity: A Key Player in Diabetes and Cancer


Obesity is a common predisposing condition to cancer and diabetes. Excess body weight is associated not only with diabetes but also with increased cancer mortality and an increased incidence of endometrial, colorectal, breast, thyroid, and renal cancers, as well as esophageal adenocarcinoma and multiple myeloma.Adipose tissue is a "highly active endocrine and metabolic organ," consisting of adipocytes, fibroblasts, macrophages, and blood vessels that produce inflammatory cytokines.5 As a result, obesity induces a state of chronic, low-grade inflammation.5 Diabetes is also associated with a low-grade proinflammatory state, which could be a "key factor in encouraging tumorigenesis."3

The Impact of Diabetes Drugs


Antihyperglycemic medications may be implicated in the development of cancer.

Drug Name/Class Impact on Risk of Cancer Development
Metformin Potentially protective3,6
Insulin analogues Neutral3
Sulfonylureas Increased risk of solid tumor, colorectal, and pancreatic cancers (weak evidence)3
Thiazolidinediones Inconclusive study findings3
DPP-4 inhibitors Evidence of increased cancer risk when used as monotherapy; potential increase in cancer risk when combined with other agents, including GLP-1 receptor agonists3

Originally thought to be associated with pancreatic cancer, the Food and Drug Administration (FDA) and European Medical Association) have issued a joint statement that "assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer … are inconsistent with the current data."7
GLP-1 receptor agonists Originally thought to be associated with pancreatic cancer, the Food and Drug Administration (FDA) and European Medical Association) have issued a joint statement that "assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer … are inconsistent with the current data."7

Potential concerns about thyroid cancer, based on animal studies, but no evidence of thyroid pathology in human beings3
Insulins Cancer risk at very high doses6

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