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From OncoLog, July 2013, Vol. 58, No. 7

Treating Diabetes in Cancer Patients

By Zach Bohannan

Photo: Dr. Victor Lavis with a patient
Dr. Victor Lavis discusses diabetes management with Teresa Seale (left) and her sister, Kathy Carter. Ms. Seale has diabetes and is undergoing testing for a potentially malignant neoplasm.
Type 2 diabetes is a serious health concern for any patient—but when the patient also has cancer, diabetes may interfere with potentially life-saving cancer treatment.

Concurrent diabetes and cancer is relatively common because of the high prevalence of both conditions. However, researchers are only beginning to understand the interactions between diabetes and cancer. “There is a growing body of research on diabetes,” said Sai-Ching “Jim” Yeung, M.D., Ph.D., an associate professor in the Department of Emergency Medicine at The University of Texas MD Anderson Cancer Center. “And now cancer researchers are beginning to integrate that knowledge into our understanding of how cancer develops and responds to treatments.”

Interactions

A potentially important interaction between diabetes and cancer is the common thread of insulin signaling. Insulin is a potent promoter of cell growth and may be implicated in the development of some common cancers. Insulin-like growth factor receptors are often mutated in cancers, and the resulting dysregulation of the insulin signaling system may lead to rampant proliferation in some types of cancer.

Hyperinsulinemia, which can result from the disruption of insulin signaling or production, is a risk factor for the development and progression of several cancer types, including prostate and breast cancers. In contrast, lower insulin levels have been associated with better outcomes in diabetic patients with prostate or breast cancer.

Diabetes caused by cancer

Although many patients have diabetes long before their cancer diagnosis, it is equally as common for patients to develop diabetes because of their cancer or its treatment.

“[C]ancer researchers are beginning to integrate that knowledge [from diabetes research] into our understanding of how cancer develops and responds to treatments.”

– Dr. Jim Yeung

Cancer-related diabetes is most often associated with pancreatic cancer. In fact, the onset of diabetes in an otherwise healthy elderly patient is a potential warning sign of pancreatic cancer. Although it is currently not clear how diabetes and pancreatic cancer interact, their association is well documented.

Also linked to diabetes are tumors that secrete cytokines, especially those that secrete large amounts of interleukin-6. Although the role of cytokines in insulin signaling has yet to be fully characterized, interleukin-6 and other proinflammatory cytokines can cause insulin resistance. This resistance is possibly related to increased inflammatory signaling throughout the body.

Diabetes caused by cancer treatment

The most common cause of cancer treatment–induced diabetes is glucocorticoid therapy. According to Victor Lavis, M.D., a professor in the Department of Endocrine Neoplasia and Hormonal Disorders, nearly half of the diabetic and insulin-resistant patients treated at MD Anderson are patients whose cancer treatments include glucocorticoids.

Glucocorticoids, which reduce inflammation and affect lymphocyte development, are often used as part of the treatment for hematological malignancies and some solid tumors. Glucocorticoids are also given to prevent or treat graft-versus-host disease in patients who have received allogeneic stem cell transplants for hematological malignancies (see OncoLog, April 2013). Furthermore, glucocorticoids are frequently prescribed by oncologists to control nausea or to reduce swelling in the central nervous system.

However, in addition to their beneficial effects, glucocorticoids reduce glucose clearance and disrupt the function and survival of insulin-secreting pancreatic beta cells. These disruptions to glucose metabolism cause insulin resistance and hyperglycemia and, over time, may lead to permanent diabetes.

Many cancer patients who are treated with glucocorticoids will eventually need some sort of medication for their hyperglycemia. However, Dr. Lavis said, the question of which diabetes medication would allow the best response to cancer therapy for patients with glucocorticoid-induced diabetes has yet to be explored in clinical trials.

Treating diabetic patients with cancer

Photo: Dr. Victor Lavis with a patient
Dr. Victor Lavis examines a patient’s feet for signs of diabetes-related circulatory or neurological complications.

Many diabetic cancer patients have poorly controlled blood sugar at the time of their cancer diagnoses. These patients’ blood sugar must be brought under control before they can safely undergo cancer treatment.

Until recently, a patient’s diabetes and cancer were treated as if they were unrelated. However, physicians are finding that some diabetes treatments seem to be more effective than others for controlling blood sugar in patients with concurrent cancer. Dr. Yeung said, “Evidence is mounting that metformin is superior to other common therapies for treating diabetes in cancer patients.”

Metformin works by blocking liver gluconeogenesis rather than affecting the insulin signaling pathway. Insulin-based diabetes treatments tend to address the hyperglycemia by simply increasing insulin levels to overcome the patient’s insulin resistance.

Future directions

Because of the increasing numbers of patients with cancer who enter the clinic with diabetes or who develop hyperglycemia during their treatment, the interaction between diabetes and cancer is becoming an important research topic. However, the field is still in its infancy. Although some studies have linked hyperglycemia and diabetes to cancer treatment outcomes, few mechanisms have been elucidated.

Furthermore, there are currently no standard guidelines for the treatment of diabetes in cancer patients. Metformin is preferred on the basis of experience and preliminary research, but it is currently unclear whether metformin is useful in all cases of concurrent diabetes and cancer. Much more research is needed.

Prevalence of Diabetes and Cancer

The U.S. Centers for Disease Control and Prevention estimates that 25.8 million people in the United States, or 8.3% of the population, have diabetes.

The American Cancer Society estimates that 12.5 million Americans have a history of some type of invasive cancer.

FURTHER READING

Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33: 1674–1685.

He XX, Tu SM, Lee MH, Yeung SC. Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients. Ann Oncol. 2011;22:2640–2645.

For more information, call Dr. Victor Lavis at 713-792-2841 or Dr. Jim Yeung at 713-745-9911.

Other articles in OncoLog, July 2013 issue:

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