The Connection Between Diabetes and Cancer: What We Know So Far

The Connection between Cancer and Diabetes

Diabetes and Cancer May Have a Greater Association than We Previously Thought or Knew

Every year, about 1.5 million new cases of diabetes are diagnosed in the United States according to the CDC. And according to reports by the American Cancer Society, about 1.96 million cancers were diagnosed in 2023.

A Statement from the American Diabetes Association and the American Cancer Society

In 2010, the American Diabetes Association (ADA), along with the American Cancer Society (ACS), convened a consensus regarding diabetes and cancer, concluding the following: diabetes (primarily type 2, though type 1 is not completely excluded) is associated with increased risk of liver, pancreas, endometrium, colon and rectum, breast, and bladder cancer. The association between diabetes and cancer may be partly due to shared risk factors such as aging, obesity, diet, and physical inactivity, but the specifics of the association between the two remain a mystery.

It is unclear whether the association between diabetes and cancer is direct (e.g., due to hyperglycemia directly causing cellular damage), whether diabetes is a marker of underlying biologic factors that may confer a higher cancer risk, or whether the cancer-diabetes association is indirect and due to common risk factors, such as obesity.

The Relationship between Diabetes and Pancreatic Cancer

People with diabetes, particularly type 2 diabetes, are at an increased risk for several types of cancer. One of the most serious is pancreatic cancer. The relationship between pancreatic cancer and diabetes is complex and may be bi-directional, involving both an increased risk of developing pancreatic cancer among people with diabetes, and the potential for pancreatic cancer to induce diabetes. Some studies have shown that people with long-standing type 2 diabetes may have one and a half to two times higher risk of developing pancreatic cancer compared to non-diabetics. Research is still ongoing.

Evidence developed since the early 2000s supports a link between new-onset type 2 diabetes and pancreatic cancer. Strikingly, the data further indicated that the risk of pancreatic cancer in individuals 50 years and older with new-onset diabetes can be six to eight times higher than in non-diabetics within three years of diabetes diagnosis. This finding aligns with the fact that almost 25% of people with pancreatic cancer are diagnosed with diabetes within six months to 36 months before being diagnosed with pancreatic cancer. Additionally, one in one hundred people with new-onset diabetes will develop pancreatic cancer within three years.

Given the potentially dire implications of a pancreatic cancer diagnosis, developing strategies for early detection of the disease are actively being evaluated. Testing for cancer at the time of diabetes diagnosis may result in identifying pancreatic cancer at an earlier stage, potentially dramatically changing the clinical trajectory of the patient.

Diabetes and Other Types of Cancer

Other common types of cancer observed in people with diabetes include:

  1. Liver Cancer: People with diabetes, especially those with poor glycemic control, have a higher risk of developing liver cancer. This may be due to the association between diabetes and non-alcoholic fatty liver disease (NAFLD) or as it is now called, metabolic dysfunction-associated liver disease (MASLD) and cirrhosis.
  2. Colorectal Cancer: Diabetes, particularly type 2 diabetes, is linked to an increased risk of colorectal cancer. This risk is possibly related to factors like obesity, chronic inflammation, insulin resistance, and changes in gut microbiota.
  3. Bladder Cancer: Studies have shown that people with diabetes may have a higher risk of bladder cancer, potentially influenced by factors such as hyperinsulinemia, and chronic inflammation.
  4. Breast Cancer: There is an increased risk of breast cancer in women with diabetes. This association may be influenced by obesity, hormonal changes, and insulin resistance.
  5. Endometrial Cancer: Women with diabetes are at an increased risk of endometrial cancer. This risk is likely due to factors like obesity and increased insulin resistance.
  6. Kidney Cancer: People with diabetes have a higher incidence of kidney cancer, which may be related to obesity, hypertension, and chronic kidney disease often seen in diabetes.

Some Cancer Therapies May Increase the Risk of Developing Diabetes

Another factor to consider while we are on this topic is that some cancer therapies are associated with an increased risk of developing diabetes as a side effect.

Corticosteroids, for instance, are potent anti-inflammatory medications, commonly added to chemotherapy regimens to mitigate side effects such as nausea, and can be used to treat some kinds of cancer pain. These are useful medications with excellent anti-inflammatory effects, but can cause significant insulin resistance, especially at high doses, and can thereby raise blood glucose causing temporary or even long-standing hyperglycemia.

Other cancer therapies, especially immunotherapies including immune checkpoint inhibitors that manipulate the immune system to recognize and attack cancer cells, have also been shown to have the potential to lead to insulin-dependent diabetes (similar to type1 diabetes).

As everything discussed in the medical field, it should come down to a risk vs benefit discussion, and with the advanced technology and newer treatment modalities available to manage diabetes, cancer therapy should not be withheld due to the potential risk of diabetes or hyperglycemia. Overall, hyperinsulinemia, insulin resistance, chronic inflammation, chronic hyperglycemia, and obesity seem to be the main risk factors linking diabetes and cancer.

Can GLP1s Lower Cancer Risk?

On July 5th, 2024, a study published in the medical journal JAMA stated that GLP-1 RAs were associated with a lower risk of developing several obesity-associated cancers in people with type 2 diabetes when compared to insulin. The study included more than 1.6 million people and the follow-up period spanned up to 15 years. It showed risk reductions for:

  • Gallbladder cancer
  • Meningioma
  • Pancreatic cancer
  • Hepatocellular carcinoma
  • Ovarian cancer
  • Colorectal cancer
  • Multiple myeloma
  • Esophageal cancer
  • Endometrial cancer
  • Kidney cancer

No decrease in cancer risk was associated with GLP-1 RAs compared with metformin, and in fact there was an increased risk of kidney cancer, so those at risk for kidney cancer should use precaution with GLP-1 RAs.

The Importance of Cancer Screening

These associations highlight the importance of regular cancer screenings and preventive measures in people with diabetes, especially those who may have additional risk factors for specific types of cancer. It is essential for people with diabetes to manage their blood sugar levels, maintain a healthy weight, and engage in regular physical activity to mitigate these risks as much as possible.

We also still require a better understanding of whether diabetes influences a cancer prognosis above and beyond the prognostic conferred by each disease state independently.

You can find more information and screening recommendations for the types of cancer that can be more prevalent in people with diabetes here:

Hopefully, as more research is conducted, we will have the data, tools, and resources to make earlier diagnoses, offering better treatment outcomes for people with and without diabetes.

 

 

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