A large Danish study has found that cancer increases the risk of new-onset type 2 diabetes, especially certain types of cancer, most notably pancreatic malignancies.
"Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers," said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, Denmark, in a statement.
"It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations," said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS, Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School (EVMS) in Norfolk, Virginia, when asked for comment by Medscape Medical News. Siraj also noted that "in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation."
Diabetes Risk Highest With Pancreatic Cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% CI, 1.03 - 1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI 3.62 - 6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22 - 1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10 - 1.84).
The link with pancreatic cancer was not surprising, said Sylow.
Siraj agreed, noting that a few studies have shown a strong association. "It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes," he said. "The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance," said Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at EVMS.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is "an intriguing finding," he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
"We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes," said Sylow in the statement.
Increased Mortality Risk in Those With Cancer and Type 2 Diabetes
Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
"We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic," Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. "Early intervention could have an impact on certain cancer patients," said Johansen.
Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it's managed by a primary care physician or endocrinologist, "as proper treatment may contribute to better outcomes of the cancer," said Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
Diabetes Care. 2022;45:e105-e106. Full text
Alicia Ault is a Lutherville, Maryland-based freelance journalist whose work has appeared in publications including JAMA, Smithsonian.com, The New York Times, and The Washington Post. You can find her on Twitter: @aliciaault.