Double Jeopardy: Treating Diabetes & Cancer

Diabetes is already a complex chronic disease that requires a diligent treatment regimen. When cancer is added, diabetes management may require a Herculean effort both for the patient and the endocrinologists who treat them.

Diabetes is one of the more complex chronic diseases, requiring treatment through not only lifestyle and dietary measures, but a finely tuned medication regimen that may include insulin and one or more oral agents.

But add cancer on top of it, and diabetes management may require what feels like a Herculean eff ort both for patients and the endocrinologists who treat them. Chemotherapy and pain drugs can aff ect glucose homeostasis and insulin sensitivity, drug-drug interactions can interfere with the patient’s tolerance for diabetes drugs, and the decreased appetite, nausea, vomiting, and consequent weight loss of both illness and cancer treatment can wreak havoc with a patient’s blood glucose.

Corticosteroids

When it comes to cancer drugs, corticosteroids are the 800- pound gorilla in the room, says Victor Lavis, MD, professor in the Department of Endocrine Neoplasia and Hormonal Disorders at the University of Texas MD Anderson Cancer Center in Houston. “They’re a major part of chemotherapy and widely used for amelioration of nausea and vomiting associated with chemotherapy, as well as to suppress neurological symptoms when cancer has metastasized to the spine or brain. And they induce hyperglycemia.”

An observational study appearing in the December 2013Current Oncology found that blood glucose rose significantly in the hours following administration of corticosteroids in cancer patients with diabetes, as detected by blood glucose checks taken six hours after the patients received the drugs. The researchers found that the patients were still hyperglycemic 20 hours after administration.

This kind of spike is to be expected, but it can pose problems if the patient is receiving cyclic chemotherapy, says Catherine M. Edwards, MD, FACE, program director and associate professor of endocrinology in the Division of Endocrinology, Diabetes, and Metabolism at the University of Florida College of Medicine, in Gainsville, Fla.

“Within the first 24 hours, blood glucose will go way up, and then come down slowly after the last steroid dose, generally not coming back to baseline for about four days,” she says. “So patients who get chemotherapy every two weeks will have a fairly significant portion of time where blood glucose is very high.”

The simple answer, then, is insulin, she says. “Insulin is by far the most flexible and powerful way to address that. Patients with type 1 will need to adjust their dose. Patients with type 2 who are already taking oral agents at baseline will need to add insulin, but only during that period when their blood glucose is high.”

However, “simple” doesn’t necessarily mean “easy,” especially for patients with type 2 who have never taken insulin before, she adds. “They will need to learn how to take shots, and they are already dealing with a host of issues because of their cancer. That’s where we come in as physicians and make sure they have the right education and motivation to treat themselves.”

Joel Zonszein, MD, director of the Clinical Diabetes Center at Montefiore Medical Center in New York, treats patients with type 2 with basal insulin. “I like insulin for the simple fact that it’s anabolic,” he says. “While the patient is losing weight from the cancer and cancer treatment, the insulin will strengthen muscles and increase caloric reserve in fat cells.”

He adds that bolus insulin requires checking blood glucose more frequently than patients who are already grappling with multiple treatments and therapies may be willing to accept.

“Checking blood glucose can be painful, so I try to keep the insulin to one shot a day and the blood glucose check to one a day at the peak of insulin so I know whether there needs to be an adjustment,” Zonszein explains. He notes that some patients may focus on their diabetes care as a distraction from the stress of coping with cancer.

“I’ve seen patients get compulsive about their blood sugars. They want to get better, so they focus on their diabetes because they can control that better than their cancer,” he says. Keeping insulin shots and blood glucose checks to one per day each may help avoid such a preoccupation.

“It comes down to taking an individual approach with a high degree of flexibility based on what patients need and can handle,” Edwards says. “One day may be very different from the next. The patient should be instructed to monitor his or her blood glucose and stay in close contact with the physician who is managing the diabetes.”

How Much Control?

Given hyperglycemia’s deleterious effects on the body, it’s natural to want to control blood glucose in patients with diabetes as much as possible. But when cancer is added to the mix, there is more at stake. Several studies of cancers as disparate as small cell lung cancer and breast cancer note an association between hyperglycemia and poor outcomes in patients with diabetes and cancer. Hyperglycemia raises the risk of infection as well.

“If your sugar is high, there is a lot of food for cells, whether it’s bacteria or cancer cells, to help them grow,” says Kristi Silver, MD, associate professor of medicine in the Division of Endocrinology at the University of Maryland School of Medicine in Baltimore. “Now consider someone who might be neutropenic from the cancer treatment.”

Lavis agrees. “If there is a risk of infection or the patient is neutropenic, I’d be keen to get the blood glucose down to below 180 mg/dl in short order because blood glucose that high diminishes host resistance to infection.”

However, there can be such a thing as too much control, depending on the cocktail of medications the patient is taking, says Robert Sargis, MD, PhD, assistant professor of medicine in endocrinology at the University of Chicago School of Medicine.

“Pain medications can cause constipation that affects patients two-fold. It can make them not want to eat, but also, by slowing intestinal motility, it’s possible that narcotics can delay absorption of nutrients. This can lead to a mismatch in insulin delivery and glucose absorption. Then the patient will run the risk of hypoglycemia,” Sargis says.

“The key is to avoid extremes, with no hypoglycemia and minimal hyperglycemia,” he adds. “In the context of active cancer treatment, avoidance of risk [of hypoglycemia] significantly trumps tight glycemic control. That said, I think it’s reasonable to shoot for keeping the blood sugars below the renal threshold of glucose during treatment, with intensification of therapy once the patient is on the road to recovery.”

Prognosis and Comfort

Prognosis, longevity, and quality of life are important considerations in determining glycemic goals, says Otis Brawley, MD, chief medical offi cer of the American Cancer Society in Atlanta.

“The point of very tight blood glucose control is to try to prevent complications 10, 15, 20 years down the road. But in someone with a poor prognosis or an expected longevity of just a few years, we might be more concerned with comfort and quality of life in the years they have left,” Brawley says.

Lavis agrees. “If the life span of the patient is shorter than the time it takes to get complications like renal disease, we’re less likely to fuss over getting the A1c down to below 7 mg/dl.” The goal then would be to avoid the effects of acute hyperglycemia, such as dehydration and ketoacidosis.

Prognosis will affect decisions about other drugs patients may be taking because of their diabetes and risk of diabetes-related complications. Statins in particular can be tricky, says Brawley.

“Statins and chemotherapy drugs are metabolized by the same enzymes in the liver. If the enzymes are all tied up processing a statin, that can create a backup of chemotherapies to be eliminated,” he says. “Some research suggests that it works the other way, too. If you give someone who is on a statin chemotherapy and stop the statin, they will eliminate the chemotherapy drug much more quickly. Consistency is very important.”

This could create a trickle-down effect on blood glucose depending on which chemotherapy drugs the patient is taking and how those drugs affect blood glucose and insulin sensitivity.

“I would be reluctant to begin a statin on someone who is just beginning chemotherapy,” Lavis says. “If they are already on a statin, be aware of what the effects are and watch carefully. But if not, I wouldn’t want to risk some deleterious effect or a drug interaction in the liver.”

“It comes back to general prognosis,” Silver says. “If you have a good prognosis, you may back off on statins for a short period when the patient is in acute therapy, but you don’t want to ignore their cardiovascular risk from diabetes over the long term.”

Overall, the endocrinologist should find out what the oncologist’s plans are for the patient’s chemotherapy, Sargis says. “It’s important for us to know what the planned doses and durations of treatment are, and any changes in therapy.”

“On a fundamental level, I think we need oncologists to give us a reasonable impression of what the goals of care are and the likelihood of success,” Sargis adds. “It can be very sad and hard, but it’s helpful to us to target therapeutic interventions to the prognosis. If it’s poor, I think we can feel more comfortable liberalizing goals and not burdening the patient with undue expectations.”

— D’Arrigo is a health and science writer based in Holbrook, N.Y., and a regular contributor to Endocrine News. She wrote about the debate over using insulin pens versus syringes in the April issue.

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