The connection is a two-way street
Dr. Danielle Weiss is the founder of the Center for Hormonal Health and Well-Being, a personalized, proactive, patient-centered medical practice with a unique focus on integrative endocrinology. She enjoys giving lectures and writing articles for both the lay public and medical audiences.
Diabetes and pancreatic cancer have a cause-and-effect relationship. Diabetes causes changes in cells that can lead to cancer due to the damaging effects of high blood sugar. Meanwhile, pancreatic cancer can cause diabetes by disrupting one of the key functions of the pancreas—the production of the hormone insulin, which regulates blood sugar.
This article takes an in-depth look at the connection between diabetes and pancreatic cancer, including the factors that can increase the risk of getting cancer. It also explains how pancreatic cancer is treated and prevented in people with diabetes, and vice versa.
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Diabetes is a group of diseases that causes high blood sugar (glucose), also known as hyperglycemia. It is a common disease, affecting around 37 million adults and children in the United States, or roughly 11% of the U.S. population.
Pancreatic cancer is the 10th most common type of cancer in the United States, accounting for roughly 62,000 new cases and 50,000 deaths per year. It also tends to be one of the most aggressive forms of cancer, with only 1 in every 10 people surviving for five years.
The connection between diabetes and pancreatic cancer is a two-way street, with one influencing the risk of the other.
Diabetes is caused by the disruption of how insulin is either produced or used. With type 1 diabetes, the pancreas no longer makes an adequate supply of insulin to regulate blood glucose. With type 2 diabetes, the body—particularly the liver, which produces and stores glucose—no longer responds to the effects of insulin as it should.
Insulin has several functions in the body. First, it allows glucose to enter cells to provide them with energy. Second, it increases the uptake of glucose in the liver for future use. When these functions are disrupted, glucose can rise in the blood to harmful levels.
Hyperglycemia causes damage to tissues and organs in several ways. Instead of being absorbed by cells, excess sugar is broken down in the bloodstream and releases unstable molecules known as free radicals. Free radicals directly damage cells on the genetic level and trigger chronic inflammation that can cause cells to change over time.
One of the possible consequences of this is cancer. In addition to pancreatic cancer, diabetes can also independently increase the risk of liver cancer and, to a lesser degree, colon, bladder, and breast cancer.
Compared to the general population, people with diabetes are up to twice as likely to get pancreatic cancer, according to a 2021 review in the World Journal of Gastroenterology. Even so, the overall risk is considered low.
Pancreatic cancer most often involves a type of cell known as exocrine cells that make up the ducts and glands of the pancreas. Precancerous lesions commonly develop in these tissues. While most do not progress to cancer, some do.
Cancer arising from exocrine cells leads to a highly aggressive form of the disease called pancreatic ductal adenocarcinoma (PDAC). Although it can take 10 or more years for a pancreatic lesion to turn into PDAC, it may only take 12 months for PDAC to turn metastatic (cancer has spread to other sites in the body).
Pancreatic cancer can affect other types of cells, known as beta cells. These cells in the pancreas are responsible for the production, storage, and release of insulin.
As PDAC develops, the immune system will release increasing amounts of a protein called transforming growth factor-beta (TGF-β) that instigates apoptosis (programmed cell death) in beta cells.
Under normal circumstances, apoptosis allows old cells to be replaced with new ones. But with the onset of pancreatic cancer, the rate of apoptosis is increased, causing beta cells to die faster than they can be replaced.
This decreases insulin production and leads to new-onset diabetes (meaning diabetes that occurs within three years after having no diabetes).
For many, diabetes is the first sign of pancreatic cancer. Nearly one in four people with pancreatic cancer are diagnosed with diabetes six to 36 months before being diagnosed with pancreatic cancer,
For this reason, new-onset diabetes after age 50 is today considered a warning sign for the development of pancreatic cancer.
Roughly one-half to two-thirds of people with pancreatic cancer have diabetes, of which 75% are new-onset cases. Even so, fewer than 1% of people with new-onset diabetes will go on to develop pancreatic cancer, according to the National Cancer Institute.
The relationship between diabetes and pancreatic cancer is an insidious one. On the one hand, diabetes increases the risk of pancreatic cancer while leading to poorer outcomes. On the other, when pancreatic cancer leads to new-onset diabetes, it decreases survival times compared to those with long-standing diabetes.
Pancreatic cancer shares many of the same risk factors as diabetes, including obesity, physical inactivity, smoking, alcohol use, and a high-fat diet. With that said, the risk of cancer varies significantly by whether diabetes is long-standing or new-onset.
Factors that contribute to pancreatic cancer in people with long-standing diabetes include:
By contrast, factors that pancreatic cancer in people with new-onset diabetes include:
The treatment of diabetes can be complicated when pancreatic cancer is involved, and vice versa. This is why a multidisciplinary team of specialists is needed, including cancer specialists known as oncologists and diabetes specialists known as endocrinologists.
The treatment of diabetes can change in the face of pancreatic cancer no matter if you have long-standing or new-onset diabetes. This is because, in addition to type 1 and type 2 diabetes, pancreatic cancer can lead to a third form of diabetes known as pancreatogenic diabetes or type 3c diabetes.
Type 3c diabetes is a form of diabetes caused by diseases of the pancreas or the removal of the pancreas. Without a properly functioning pancreas, the ability to control blood sugar becomes all the more complex.
Type 3c diabetes can manifest as new-onset diabetes in people with pancreatic cancer. But, it can also occur in people with long-standing type 1 or type 2 diabetes who develop pancreatic cancer.
Type 3c diabetes differs from—and can complicate—type 1 and type 2 diabetes in several ways, including:
Currently, there are no guidelines for the management of type 3c diabetes. Even so, the treatment approach tends to be more aggressive and will typically involve:
The treatment of pancreatic cancer varies little in people with diabetes compared to those without. Based on the stage of the disease, the treatment plan may involve:
The proper management of diabetes can also have a beneficial effect on people with pancreatic cancer, improving treatment response and possibly survival times.
Studies have shown that chemotherapy combined with metformin increases progression-free survival times in people with advanced stage 4 pancreatic cancer. Other researchers have found that metformin combined with chemotherapy may reduce the size of a tumor and also prevent the displacement of tumor cells that can lead to metastasis (the cancer spreading to distant organs).
There isn’t a surefire way to prevent pancreatic cancer. But that doesn’t mean you shouldn’t take steps to reduce your risks, particularly if you have chronic pancreatitis and/or a family history of pancreatic cancer.
You can potentially reduce your risk of pancreatic cancer by:
If you have diabetes, taking metformin may also reduce your risk for pancreatic cancer. Some studies have suggested that daily metformin may lower the risk by as much as 37%. Other studies have not shown the same.
Even so, metformin remains the mainstay of treatment for type 2 diabetes, and some experts argue that the benefits outweigh the risks given the generally poor outcomes associated with pancreatic cancer.
Diabetes can cause pancreatic cancer due to the damaging effects of high blood sugar on the pancreas. Diabetes can also be a consequence of pancreatic cancer, caused when a damaged pancreas cannot produce enough insulin to regulate blood sugar.
While the overall risk of pancreatic cancer is low in people with diabetes, it tends to be more serious if and when it occurs. This is especially true in people over 50 with new-onset diabetes, who not only run a greater risk of pancreatic cancer but also tend to have poorer outcomes.
Metformin, the first-line treatment of type 2 diabetes, has been shown to slow disease progression and increase survival times in people with pancreatic cancer. Some studies suggest that it may even help reduce the risk of getting pancreatic cancer.
Pancreatic cancer is often "invisible" until the disease is advanced. In fact, more than half of all cases in the United States are diagnosed when the cancer has already metastasized.
It is for this reason that you should seek screening if you are at high risk of pancreatic cancer. People at high risk—such as those who have a first-degree relative with pancreatic cancer—are typically advised to undergo a magnetic resonance imaging (MRI) scan along with endoscopic ultrasonography (EUS) performed under mild anesthesia.
Having diabetes—even new-onset diabetes—is not an indication for screening for pancreatic cancer. Even so, some health experts have proposed a score-based system in which age, the amount of weight loss, and the rise in blood sugar may warrant investigation in people with new-onset diabetes.
If in doubt about your risk of pancreatic cancer, speak with a healthcare provider.
There are usually no symptoms in the early stages of pancreatic cancer. Later-stage symptoms can often be nonspecific (very broad symptoms that can mimic other conditions) and may include:
Scientists still don't know what causes pancreatic cancer, but specific genetic mutations have been identified. Some of these are inherited (like the CDKN2A gene mutation), while others are acquired later in life. Pancreatic cancer is thought to be the result of a combination of genetics, lifestyle, and environmental factors.
According to the National Cancer Institute, only around 12% of people with pancreatic cancer will survive five years after their diagnosis. Some studies suggest that having diabetes may further decrease a person's life expectancy by a few months.
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