Isabel Casimiro, MD, is board-certified in internal medicine and works as an endocrinologist at the University of Chicago.
Diabetes can affect multiple organs, including the liver. Over time, the damaging effects of diabetes can cause the scarring of liver tissues and the gradual loss of liver function. In some people, the mounting damage can lead to hepatocellular carcinoma (HCC), the most common form of liver cancer.
Both type 1 diabetes and type 2 diabetes can independently increase the risk of liver cancer. Research indicates that people with diabetes are two to three times more likely to develop HCC than people without. The risk is further increased if diabetes is poorly controlled or left untreated.
This article looks at the connection between diabetes and liver cancer, including how high blood sugar can cause changes in the liver that lead to cancer. It also describes how liver cancer is treated in people with diabetes and ways to reduce your risk if you've been diagnosed with either type 1 or type 2 diabetes.
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Diabetes is caused by the disruption of a hormone called insulin, which the body uses to regulate blood sugar (glucose). When insufficient insulin is produced, or the body does not respond to insulin as it should, glucose levels can rise to unhealthy levels. This is known as hyperglycemia.
With hyperglycemia, the body has more glucose than it needs to fuel cells. The excess glucose will, instead, undergo a process known as oxidation, during which harmful chemicals, called free radicals, are released into the bloodstream.
Under normal circumstances, free radicals are controlled by nutrients known as antioxidants. But, with uncontrolled diabetes, free radical levels can rapidly exceed antioxidant levels and cause damage to cells and tissues throughout the body.
When the liver is affected, the damage caused by diabetes will often progress in the following stages:
HCC tends to be more aggressive in people with diabetes, partly because glucose helps "fuel" a tumor's growth. Studies have shown that cancer cells consume a tremendous amount of glucose compared to normal cells. When diabetes is involved, high glucose levels can accelerate the growth and spread of liver cancer.
As a result, diabetes can significantly reduce survival times in people with liver cancer by as much as 50%.
Diabetes also increases the risk of cancer recurrence (relapse) in people with HCC, often within the three years following curative treatment.
Cirrhosis is the leading risk factor linked to the development of HCC in people with diabetes and those without.
A review of studies concluded that people with NAFLD or NASH have a minimal risk of HCC if they do not progress to cirrhosis. By contrast, those with cirrhosis have as much as a 1 in 8 chance of getting HCC, depending on the severity of their liver damage.
Blood glucose levels also influence the risk of HCC in people with diabetes. A 2021 study from Korea involving 674,178 adults with diabetes found the risk of HCC increases in tandem with increases in blood glucose values.
This means that people who are better able to control their blood sugar over the long term generally have a lower risk of HCC than those who don't.
Based on the current evidence, the following four factors are directly linked to an increased risk of HCC in people with diabetes:
While cigarette smoking, obesity, high cholesterol, high blood pressure, and high alcohol intake are not directly linked to an increased risk of HCC in people with diabetes, they can indirectly increase the risk by promoting the onset (or worsening) of cirrhosis.
The treatment of liver cancer is the same for people with diabetes as for those without. Depending on how advanced the cancer is—classified by the cancer stage—the treatment may involve:
Maintaining optimal blood sugar control is equally important if you have diabetes. Doing so lowers the risk of cancer recurrence and increases survival times.
According to a 2013 study, 92% of people who maintained optimal blood sugar control after liver cancer treatment lived for at least three years, compared to only 70% of those who did not.
Studies have shown the diabetes drug metformin (sold under the brand name Glucophage and others) is beneficial to people with diabetes and liver cancer, increasing survival times by 64% compared to those who did not receive the drug.
The first step toward liver cancer prevention in people with diabetes is the avoidance of NAFLD. This can be difficult given 50% to 75% of people with type 2 diabetes have NAFLD (largely due to high rates of obesity in the U.S. population).
To reduce the risk of NAFLD—and, in turn, HCC—people with diabetes are advised to:
Some diabetes drugs are better at preventing HCC than others.
Chief among these is metformin, most commonly used in the first-line treatment of type 2 diabetes. Studies have shown that metformin not only improves survival times in people with HCC but can also reduce the risk of getting HCC if you are diagnosed with diabetes.
A 2013 review of studies concluded that metformin could cut the risk of HCC by half in people with diabetes. The benefits are greatest when metformin treatment begins before significant liver damage.
By contrast, insulin and sulfonylureas are linked to an increased risk of HCC (likely because the drugs are used for advanced stages of diabetes once liver damage has already occurred).
Another class of drugs that may help reduce the risk of HCC in people with diabetes is statins. These include medications like Pravachol (pravastatin) and Lipitor (atorvastatin), commonly used to treat high cholesterol.
For reasons that are not entirely clear, statins appear to inhibit the formation of cancerous tumors and may reduce the risk of HCC by as much as 44% in people with diabetes.
The American Association for the Study of Liver Diseases (AASLD) recommends liver cancer screening every six months for people with cirrhosis. This involves an abdominal ultrasound with or without supporting blood tests.
Diabetes can independently increase the risk of hepatocellular carcinoma (HCC), the most common form of liver cancer. It does so by causing the progressive scarring of liver tissues and the gradual loss of liver function (collectively called cirrhosis).
Cirrhosis is the leading cause of HCC, but other risk factors can contribute, including older age, poor blood sugar control, and having diabetes for a longer time.
The treatment of liver cancer is the same for people with diabetes as for anyone else. With that said, it is essential to maintain control of your blood sugar to improve your chances of survival.
The diabetes drug metformin is especially good at this, not only at extending survival times by 64% in people with HCC but also reducing the risk of HCC in people with diabetes by 44%.
Liver cancer is often asymptomatic in the early stages when it is most treatable. This is why it is important to routinely screen for liver cancer if you have been diagnosed with cirrhosis.
It is important to note that liver cancer can also sometimes occur in the absence of cirrhosis. For this reason, you should have your liver enzymes routinely tested if you have diabetes. Abnormally high liver enzymes may be your first sign of a liver problem needing closer investigation.
Liver cancer affects roughly 1 in 10,000 people in the United States annually. If you have type 1 diabetes, your risk of getting liver cancer is double that of the general population. If you have type 2 diabetes, the risk nearly triples.
Roughly 1 in 3 cases of liver cirrhosis in the United States involve people with diabetes. Around half of all cases of non-alcoholic fatty liver disease (NAFLD) are among people with diabetes.
People with diabetes are at increased risk of liver, pancreatic, colon, endometrial, breast, and bladder cancer. Diabetes increases the risk of these cancers and reduces survival times compared to people without diabetes.
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Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.
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