Linda Childers

When Shawn* received a diagnosis of a neuroendocrine tumor in September 2022, he never imagined that just a year later, he would also be told he has diabetes.

“My doctors believe the immunotherapy I was receiving may have induced the diabetes,” says Shawn. “I’m currently successfully managing my diabetes with the help of an insulin pump.”

Although rare, Shawn’s dual diagnoses have been documented in other patients who undergo immunotherapy, which rarely cause the immune system to turn on certain tissues — including the islet cells in the pancreas which produce insulin.

Results of research published in the journal 

 found that after treatment with checkpoint inhibitors, approximately 1% of patients developed a type of insulin-dependent diabetes.

Dr. Zoe Quandt, an endocrinologist at the University of California San Francisco (UCSF) Medical Center, cares for patients, including Shawn, who develop hormonal side effects from their cancer treatments.

She says both cancer and subse- quent treatments can cause metabolic changes that trigger or aggravate high blood sugar.

“Immunotherapies have proven to be effective cancer treatments that work by enabling the patient’s own immune system to fight cancer,” Quandt says. “Since immunotherapies stimulate a patient’s immune system and kill cancer cells, they can also cause elevated blood sugar levels and present a challenge for physicians to treat.”

In addition to checkpoint inhibitors, research has found that medications used to fight cancer, including corticosteroids and phosphoinositide 3-kinase (PI3K) inhibitors, can also cause diabetes. Some forms of chemotherapy, including 5-fluorouracil, asparaginase, busulfan and cisplatin, have also been linked to high blood sugar levels.

Dr. Matthew P. Wahl, an endocrinologist with University of Utah Health in Salt Lake City, says corticosteroid medications such as dexamethasone, often prescribed to combat nausea during cancer treatment, have been shown to raise blood sugar levels in some patients.

“If patients see a rise in blood sugar, we will work with them to adjust their insulin (dosing as needed),” Wahl says. “In some cases, drug-induced diabetes may be reversible after the medication is discontinued, while in other cases it’s a permanent condition.”

Although secondary diabetes can be a side effect of some of the therapies used to treat cancer, Wahl says other patients with cancer may have undiagnosed diabetes prior to beginning treatment.

One study, published in 2021, found that approximately half of patients with cancer reported new onset of type 2 diabetes after cancer diagnosis and treatment.

“We know there are shared risk factors for cancer and diabetes including advanced age, obesity and smoking,” says Dr. Kevin Schleich, a clinical pharmacy specialist at the University of Iowa Hospitals & Clinics in Iowa City. “Some (patients with cancer) may have an underlying case of diabetes that wasn’t previously diagnosed or high blood sugar levels that were elevated to diabetic levels after beginning cancer treatment.”

Schleich says doctors closely monitor each patient’s daily blood sugar and A1C levels when they’re undergoing cancer treatment to ensure blood sugar levels are well-controlled and that patients don’t develop ketoacidosis.

“While we don’t want to see high glucose levels in the long-term, they’re sometimes tolerable for a couple of days, when a patient with type 2 diabetes is undergoing cancer treatment,” Schleich says. “If they’re already on insulin, we may slowly increase their insulin dosages, where other previously insulin-naïve patients may need the addition of insulin on cancer therapy days.”

Quandt and Dr. Robert Rushakoff, clinical director of the UCSF Diabetes Clinic at Mount Zion, collaborated with the UCSF Infusion Center to develop a hyperglycemia management protocol for patients with cancer experiencing elevated blood sugar levels. The protocol is provided through an urgent care site within the infusion center, and Quandt says their model can be replicated at other infusion centers to offer a rapid response for patients who experience a rapid rise in glucose levels.

According to the protocol, Quandt says the urgent care team must decide if the patient with cancer experiencing hyperglycemia should be sent to the emergency department or if they can safely be treated at the infusion center.

“The protocol helps providers determine the amount of insulin and fluids to give the patient so they can safely continue with their cancer treatment that day,” Quandt says. The protocol also promotes patient education by encouraging staff to teach patients how to use a glucometer and insulin pen and to provide individualized nutrition counseling.

Diet and Lifestyle Changes Can Make a Difference 

With both diabetes and obesity on the rise, the World Health Organization recently noted that obesity may overtake smoking as the main risk for preventable cancer. High-quality diets have been shown to play a crucial role in preventing obesity, managing diabetes and lowering the risk of cancer.

According to the American Cancer Society and the American Diabetes Association, a diet containing fresh vegetables, whole grains, fruits, low-fat dairy or non-dairy products and lean meats can benefit patients who have been diagnosed with both cancer and diabetes. This type of diet can also reduce the risk of heart and kidney disease because diabetes, particularly type 2, increases the risk of developing these conditions.

“We always encourage patients to meet with a dietitian who can help them adopt a balanced meal plan,” Schleich says. “A dietitian can work with patients to devise an individual and consistent plan while also addressing issues such as what foods to eat in the event they feel nauseous or fatigued.”

Schleich notes that a patient’s blood sugar levels need to be well-managed during cancer treatments and that loss of appetite, a common side effect of cancer therapy, can lead to low blood sugar levels.

One recent study found that patients who had both advanced breast cancer and diabetes reported better long-term outcomes when their blood sugar levels were well- controlled, as opposed to those with uncontrolled blood sugar levels.

Quandt says this is where an individualized approach to helping patients with cancer control their diabetes comes into play.

“We like to see a patient’s A1C under 7% and we encourage them to give up habits such as smoking and alcohol that can make their prognosis worse,” she says. “Yet when a patient has done all of that and says sweets are the only thing left that gives them happiness, we’re going to determine how they can continue to enjoy ice cream without raising their blood sugar.”

One of the first things Quandt’s patient Shawn did shortly after receiving his cancer diagnosis was meet with a dietitian. He says the guidance he received was invaluable.

“My initial focus was on improving my diet and, as a result, managing my diabetes has been easier than I anticipated,” he says. “The dietitian

I consult with specializes in cancer care and believes my dietary focus will improve my long-term outcome.”

By learning how to best manage side effects of his cancer treatments and diabetes through diet, Shawn says he’s also been able to maintain an active lifestyle. 

“Whenever I have free time, you can find me on the tennis courts or on my mountain bike,” he says. “I can’t emphasize enough how important good nutrition is. I truly believe it’s the Holy Grail to successfully treating and keeping cancer at bay.”

Although researchers have established a clear link between diabetes and cancer, Quandt says there’s a need for continued research into why some cases of diabetes seem to be a side effect of cancer treatments and what can be done to reduce the risk.

“Some research shows the diabetes medication metformin is associated with a decreased risk for all cancers,” Quandt says. “With other agents, a lot of the research is inconclusive as to whether they can cause cancer or prevent it.”


Quandt notes some previous studies have also shown a link between long-term increased insulin levels raising the risk of certain types of cancer, including breast, prostate and colorectal.

Schleich says cancer treatments, as well as research on survival rates for cancer and diabetes, have improved since he was a resident in 2013.

“The field has seen significant improvements with immunotherapy and other treatments that have greatly improved cancer survival rates compared with what they were a decade ago,” he says.

LaCrecia Day of Birmingham, Alabama received a diagnosis of triple-negative breast cancer in October 2020 after discovering a lump.

“I went to a clinic that did 3D imaging, and they provided same-day results,” Day says. “The radiologist saw something on the imaging that was probably cancer and sent the images to a pathologist for a second opinion.”

LaCrecia Day was diagnosed with triple-negative breast cancer in 2020, and then with diabetes. 

Photo credit: Jennifer Alsabrook-Turner of Bang Images

From that moment, things moved fast. Day had a biopsy three days later and was referred to a surgeon, who thought the best course of action was to shrink the tumor through four weeks of chemotherapy before scheduling surgery.

“By the time I had my surgery, the tumor had doubled in size and was over 5 centimeters, and my diagnosis changed from stage 1 to stage 2 cancer,” Day says.

When a hematoma developed in her chest after surgery, her doctor discovered she had an A1C of 8% and subsequently diagnosed her with diabetes.

“I was initially prescribed metformin and later Jardiance (empagliflozin) and Ozempic (semaglutide), and my A1C is now below 7% and continuing to decrease,” she says.

Day also met with a nutritionist to determine foods that would keep her diabetes in check but also be palatable during her cancer treatments.

“I found eating fish and vegeta- bles satisfied my appetite and were easier to digest than meat and processed foods,” she says.

With her cancer now in remission, Day says her doctors believe her diabetes is also reversible.

“My advice to other patients affected by diabetes and cancer is to ensure all of your doctors are communicating so that you can get quality care,” Day says. “Cancer can be an isolating experience and it really helped me to connect with NowIncluded.com, a Black online health community platform, where I was able to share my story and read stories from other (patients with cancer).”

Schleich agrees, adding that patients with a diagnosis of both cancer and diabetes should never assume their other health providers know about the other services they’re receiving and medications they’re taking.

“Patients need to be proactive and ensure they communicate with their providers about any health changes that have occurred since their last appointment,” he says. “Take notes when you talk with your doctors and be sure to ask questions.”

Shawn says he has what he calls a “baseball team” of nine multidisciplinary providers on his diabetes/ cancer care team.

“The ninth slot is the designated hitter when I need to sub in a specialist,” he says. “I think it’s important to treat the whole body, and I have an oncologist, nuclear oncologist, immunotherapy oncologist, therapist, psychiatrist, nutritionist, acupuncturist and massage therapist on my winning team.”

* For the purposes of anonymity, Shawn will be referenced by first name only.

For more news on cancer updates, research and education, don’t forget to 

Articles

Patients "need to be proactive" as they coordinate care between two diseases.

First Cancer, Now Diabetes

When Marissa Willis began feeling pain on her left side in May 2013, she initially thought she might have pulled a muscle during one of her workouts. 

At 38, the mother of two was in good health and exercised regularly. Yet when the pain persisted, Willis headed to her local urgent care center and was shocked when X-rays revealed a mass on her left kidney.

“I saw my primary care provider the next day for a sonogram, and the next two weeks were a whirlwind of appointments, scans and tests at the University of Kansas Medical Center,” says Willis, who lives in Blue Springs, Missouri. “Ten days later, I had a radical left nephrectomy to remove both the tumor and my left kidney.”

After her surgery, Willis was doing well until a follow-up imaging test 10 months later found a small spot on her lung.

Marissa Willis experienced high blood pressure and an underactive thyroid during kidney cancer treatment, both of which were manageable.

“Since the spot was less than a centimeter, my oncologist decided it was reasonable to watch the mass and see if would grow,” Willis says.

Three years later, in 2017, an imaging test determined another spot on her lung was large enough to biopsy. Test results found the cancer had metastasized to her lung, and Willis began four cycles of high-dose interleukin-2, a form of immune-stimulation therapy.

It wasn’t until Willis was prescribed her current drug regimen of 

Votrient (pazopanib), a tyrosine kinase inhibitor

 that targets cancer-supporting blood vessels, that she began to experience side effects from her cancer treatment.

“I had never had high blood pressure before, but after being on Votrient for a short time, I was diagnosed with both hypertension and an underactive thyroid,” Willis says.

Although tyrosine kinase inhibitors and checkpoint inhibitors have proven to be extremely effective in treating patients with renal cell carcinoma, they also carry the possibility of side effects, which can be worrisome for patients.

In Willis’ case, her care team had discussed potential side effects with her in advance and monitored her bloodwork and blood pressure levels so that any changes with her health could be immediately addressed.

“My doctor put me on medication to lower my blood pressure and treat my underactive thyroid. I monitor my blood pressure daily and have my thyroid-stimulating hormones levels checked on a regular basis,” Willis says. “While I will be on both medications indefinitely, I’m happy to be living a pretty normal life.”

Because treatments for kidney cancer, including immunotherapies and tyrosine kinase inhibitors, carry the risk of side effects, it’s important for patients and their oncology care team to weigh the risks versus the benefits of each treatment, according to Dr. Thomas Hutson, director of the urologic oncology program and co-chair of the Urologic Cancer Research and Treatment Center at Baylor University Medical Center in Dallas and a professor of medicine at Texas A&M University School of Medicine in Bryan.

“Immunotherapies and (tyrosine kinase inhibitors) have shown success in treating metastatic cases by shrinking tumors and offering many patients remission and long-term survival,” Hutson explains. “Many of the common side effects tend to be fatigue, skin rashes and chronic muscle-related issues such as cramping or joint pain.”

Findings from a study published in the medical journal 

 in 2021 showed that approximately 40% of patients taking checkpoint drugs as immunotherapy develop acute and chronic complications such gastrointestinal side effects, rash, arthritis or endocrine dysfunction.

If a patient encounters more severe side effects, Hutson says doctors will look at adjusting or lowering the dose of the medication, making the side effects manageable.

“Some patients are reluctant to lower their medication dose, mistakenly believing it will also lower the effectiveness of the medication,” Hutson says. “This isn’t the case, and when prescribing treatments, doctors take (into) consideration a patient’s quality of life. If the medications are taking too much of a toll on a patient and adversely affecting their health, a decision will be made about stopping the medication, since we don’t want to continue a high-dose drug regimen that will cause patients to suffer unnecessarily.”

Hutson tells patients their cancer journey is “a marathon, not a sprint,” and if they need to stop an immunotherapy or tyrosine kinase inhibitor drug — at least temporarily — they can later resume treatment on a lower dose or sometimes even a different drug. 

patients should always report side effects

“Reducing dosages isn’t bad,” Hutson says. “In clinical trials, dose reductions are quite common, so we always tell patients the medication dose they start at may not be the same dose they stay on. In fact, two-thirds of all (patients with cancer) need to be switched to a lower dose. We strive to balance the side effects with safety and quality of life.” 

Information from clinical trials shows that the rates of response and length of time to when there may be progression of a tumor do not seem to differ among patients who need a dose reduction due to side effects compared to those who may not.

In rare cases, Hutson notes that immunotherapy drugs, especially when combined, can trigger a more severe autoimmune response causing inflammation of the lungs, liver or colon. 

This was the case for Chase Griffith, 45, of Dallas, who was diagnosed with kidney cancer in December 2018. After Griffith underwent a complete nephrectomy, his follow-up scans showed no sign of cancer — until April 2021, when an MRI and CT scan found that the cancer had metastasized to Griffith’s liver.

After meeting with doctors at The University of Texas MD Anderson Cancer Center in Houston and UT Southwestern Medical Center in Dallas, Griffith decided his best course of action was to begin a triple-medicine clinical trial using two immunotherapy drugs, Opdivo (nivolumab) and Yervoy (ipilimumab), combined with the tyrosine kinase inhibitor Cabometyx (cabozantinib). 

The phase 3 clinical trial is comparing treatment with Yervoy and Opdivo followed by Opdivo alone to treatment with Yervoy and Opdivo followed by Opdivo with Cabometyx in patients with untreated renal cell carcinoma that has spread to other parts of the body. 

Chase Griffith's cancer pread to his liver, which led to treatment with immunotherapy and tyrosine kinase inhibitors. 

Researchers hope to determine if the addition of Cabometyx to the usual treatment will make the therapy more effective at stopping the growth of tumor cells.

“When I went in to get my third dose of the treatment regimen, I had bloodwork done and my oncologist found that (my) liver enzymes were off the charts,” Griffith recalls. “Basically, the immunotherapy caused my immune system to attack my healthy liver tissue.”

Doctors told Griffith they would immediately stop the therapy and begin a course of steroids to suppress the immune response. Because Griffith had been cautioned ahead of time about potential side effects, he wasn’t surprised and believed he was in good hands with his oncology team.

“I was put on 200 milligrams a day of prednisone that I took for several months before doctors began tapering me off the medication,” Griffith says. “I got down to 10 milligrams in February of this year and started having the same side effects, including insomnia and an elevated heart rate. After going to an urgent care center, I learned that my liver enzymes were even higher than before.”

Griffith was hospitalized and given both prednisone and the high-level immunosuppressant CellCept (mycophenolic mofetil), which is often prescribed to prevent organ rejection after transplantation. He remained on the drugs for several months.

Because he has chromophobe renal cell carcinoma, a rare form of kidney cancer, Griffith knows his doctors are using novel approaches to create targeted therapies that stop or slow the growth of his cancer.

“This past February, doctors started me on another (tyrosine kinase inhibitor), lenvatinib (Lenvima), and an mTOR (inhibitor) therapy, everolimus, that have resulted in a 20% shrinkage in my tumor,” Griffith says. “Today, I feel good, and my doctor says I have no new tumors and that my existing tumors have stabilized.”

Frequent Communicatoin Is Key to Managing Side Effects 

According to Laura Wood, an oncology nurse and former renal cancer center research coordinator at Cleveland Clinic Taussig Cancer Center, high blood pressure, or hypertension, can be a side effect of some of the multikinase inhibitors used to treat kidney cancer since they act by affecting the blood vessels in tumors and can also have effects on normal blood vessels that regulate blood pressure. 

These drugs include Sutent (sunitinib malate), Lenvima and Inlyta (axitinib). In addition, Wood notes that a class of drugs known as mTOR inhibitors, including everolimus, rapamycin (sirolimus) and temsirolimus (CCI-779), can often cause side effects such as elevated blood sugar, cholesterol and triglycerides.

“We tell patients in advance they shouldn’t be surprised if they develop any of these conditions while undergoing cancer treat- ment,” Wood says. “They’re very manageable conditions, and (the patient’s) bloodwork and symptoms improve after adjustments are made to their cancer treatment and medications are given to treat the side effects. Some side effects may result in long-term symptoms which require ongoing discussions with your oncology team or other specialists to manage.”

Wood says it’s crucial for health care providers to provide patients with kidney cancer with early and ongoing education regarding potential side effects and for patients to report these as soon as possible to obtain relief and avoid any organ damage or other long-term problems.

Reporting side effects can also help researchers better understand side effects and develop additional strategies on how to best manage them. 

In 2017, the Severe Immunotherapy Complications Service was launched at Massachusetts General Hospital in Boston to treat and study patients with immune complications from immune checkpoint inhibitors. Many other cancer centers have similar programs and multidisciplinary teams to manage immune-related side effects.

Dr. Naomi B. Haas, an oncolo- gist and director of the prostate and kidney cancer program at Penn Medicine and a professor of medicine at the Hospital of the University of Pennsylvania in Philadelphia, notes that in rare cases, side effects might even be considered something of a positive.

Haas cites an analysis of clinical trials conducted at Dana-Farber Cancer Institute in Boston showing that patients with advanced kidney cancer who were diagnosed with high blood pressure and prescribed medications called angiotensin system inhibitors, including angiotensin-converting enzyme inhibitors and angiotensin system blockers, lived longer and had better outcomes than patients who weren’t diagnosed with hypertension and treated with those medications.

Even when patients experience milder side effects, Haas says they should discuss changes with their oncology team. 

The Kidney Cancer Association offers a printable side effect tracker on its website, www.kidneycancer.org, to make it easier for patients to track their symptoms and inform their oncology team about symptom severity and how often symptoms are occurring.

“In some cases, patients can lose their sense of taste and say their food tastes like cardboard,” Haas says. “As a result, they aren’t going to eat as much and will ultimately lose weight, which we don’t want.”

To address this, Haas says oncologists will typically ask a patient to cease taking their medication for a few days to determine whether it’s the drug or the disease that’s causing the problem. If it’s the medication, Haas notes that drugs such as mirtazapine can be prescribed to help stimulate a patient’s appetite.

Diarrhea is another common side effect that Haas says can impact both a patient’s physical and emotional health. Haas says patients should never be embarrassed to discuss any changes in their health with their oncology team.

“We don’t want patients to be miserable or afraid to venture out socially because they’re experiencing diarrhea,” Haas says. “We can prescribe probiotics and advise changes to their diet to remedy their situation. In severe cases, we might begin steroid therapy.”

In cases of renal cell carcinoma, although side effects can initially seem scary, Haas says most are treatable and are outweighed by the benefits patients receive from tyrosine kinase inhibitors and checkpoint inhibitors.

Willis says she has been feeling “pretty good” over the last 2-and- a-half years, especially since her side effects are much more manageable now.

“I know my body well enough on (treatment) now that I’m living a pretty normal life,” she says. “Ironically, being active, working out, that helps energy levels and those side effects. ... I’ll be on this indefinitely, probably until either I don’t need it, or it stops working.”

For more news on cancer updates, research and education, don’t forget to 

Newer drugs for kidney cancer have proven extremely effective but can cause unwanted symptoms that affect safety and quality of life.

Linda Childers

First Cancer, Now Diabetes

Risk Versus Reward: Managing Side Effects of Kidney Cancer Treatments

Latest News