Diabetes and Liver Disease: What Is the Relationship?

There is a close association between diabetes and liver disease. In some cases, diabetes can cause progressive liver scarring, leading to a liver injury known as cirrhosis. Diabetes can also speed the progression of liver disease, increasing the risk of severe and potentially life-threatening complications like liver failure or liver cancer.

In addition, there is evidence that having a liver disease can contribute to the onset of diabetes.

Studies suggest that anywhere from 30% to 40% of people with liver cirrhosis in the United States have diabetes and that having diabetes independently increases the risk of complications and death from liver disease.

This article takes an in-depth look at the connection between diabetes and liver disease, including how one may increase the risk of the other. It also explores the various treatment options and what you can do to reduce the risk of liver disease if you are living with diabetes.

Connection Between Diabetes and Liver Disease

Diabetes is a group of diseases that occurs either when the pancreas does not produce enough insulin—the hormone that regulates blood glucose (sugar)—or the body cannot effectively use the insulin it produces. This can lead to a condition known as hyperglycemia (high blood sugar)

If left unchecked, persistently high blood glucose levels can severely damage nerves, blood vessels, tissues, and organs throughout the body.

The liver is one of the organs vulnerable to these effects. Over time, the damage caused to the liver can reduce its ability to filter toxins from the blood or maintain healthy blood sugar levels, resulting in chronic liver disease (CLD). With CLD, the damage caused to the liver is largely irreversible.

There is also a cause-and-effect relationship between diabetes and liver disease in that CLD can also play a role in the development of type 2 diabetes (the form of diabetes largely related to lifestyle factors like diet and obesity).

How Diabetes Causes Liver Disease

When diabetes is poorly controlled, the impact of hyperglycemia on the liver can be profound. The liver is especially vulnerable, in part because it both stores and manufactures glucose depending upon the body’s needs.

Under normal circumstances, the metabolization (breakdown) of blood sugar will result in toxic byproducts known as free radicals, which are damaging to the body but can be controlled by nutrients known as antioxidants.

When blood sugar levels are high, free radicals can exceed antioxidant levels and start to inflict damage on cells, referred to as oxidative stress. Oxidative stress, in turn, triggers inflammation which can cause changes to the liver over time.

The liver is susceptible to the damaging effects of diabetes because it is tasked with warehousing sugar in the body. As such, higher levels of blood sugar translate to higher levels of free radicals, which causes higher levels of oxidative stress.

Liver damage caused by diabetes progresses in stages:

• Nonalcoholic fatty liver disease (NAFLD): This is a condition in which fat builds up in the liver, often without notable symptoms.
• Nonalcoholic steatohepatitis (NASH): This is a more severe form of NAFLD in which inflammation triggers the development of scar tissue, known as fibrosis.
• Cirrhosis: This is when fibrosis starts to interfere with the function of the liver, either partially (compensated cirrhosis) or completely (decompensated cirrhosis).
• Hepatocellular carcinoma (HCC): This is the most common form of liver cancer and affects people with diabetes at a rate up to 3 times that of the general population.
• Acute liver failure: This is when the liver is no longer functional due to cirrhosis or HCC. It is a medical emergency that can lead to multi-organ failure and death if not treated immediately.

Some people with diabetes-induced liver disease may only progress to a certain stage and no further, while others may progress to end-stage disease. People with poorly controlled or untreated diabetes are at the greatest risk of progression.

How Liver Disease Causes Diabetes

While diabetes can lead to CLD by exposing the liver to chronic inflammation and scarring, there is evidence that CLD can lead to diabetes by causing insulin resistance. This is when cells in your liver don't respond well to insulin and are less able to take up glucose as they are supposed to.

One of the liver's major functions is to maintain normal blood sugar levels by absorbing and releasing glucose as needed. Insulin is the messenger that directs liver cells to take up glucose for storage.

With CLD, the damage caused to liver cells can make them increasingly resistant (nonresponsive) to the effects of insulin. As a result, less glucose is taken up by the liver, muscles, and other tissues. In response, the pancreas will release more insulin to increase glucose uptake by cells.

Over time, however, insulin resistance can start to "wear out" pancreatic cells to where they can no longer produce enough insulin to compensate for this effect. The result is higher blood sugar levels and, ultimately, prediabetes or type 2 diabetes.

Type 2 diabetes caused by the breakdown of liver function is referred to as hepatogenous diabetes.

Risks

Diabetes and CLD are both chronic diseases, meaning that they are persistent and typically progressive. If left untreated, diabetes can increase the risk of liver disease, and liver disease can increase the risk of diabetes. The risk of comorbidity (the simultaneous occurrence of two diseases) is greater if diabetes or CLD is advanced.

Risk factors are associated with the progression of both diseases, some of which overlap.

Having diabetes and liver disease can also lead to poorer outcomes compared to having one disease on its own. According to a 2020 study in the World Journal of Hepatology, type 2 diabetes can reduce the life expectancy of people with cirrhosis by up to 40% after five years.

Conversely, having type 2 diabetes increases the risk of NAFLD by twofold to threefold.

Treatment and Management of Diabetes and Liver Disease

While there is no cure for either diabetes or chronic liver disease, both can be managed with lifestyle changes and medications. These interventions can help slow disease progression and prevent long-term complications involving not only the liver but the heart and kidneys as well.

It is well known that basic lifestyle changes—such as increased exercise, a healthy diet, smoking cessation, and alcohol avoidance—are fundamental to the management of diabetes and liver disease.

When diabetes and liver disease occur together, medications are commonly prescribed to maintain better blood sugar control. This helps reduce oxidative stress and further damage to the liver.

The choice of drug can vary based on the stage and severity of your condition. Each has its benefits and risks and may be used either in combination or on its own.

If cirrhosis is involved, the main treatments are cutting salt from your diet and taking diuretics ("water pills") like Aldactone (spironolactone) or Lasix (furosemide) to prevent the buildup of fluid in the abdomen (called ascites). In severe cases, you may need to have the fluid drained from your belly with a tube.

In cases of liver cancer, treatment options include radiation therapy, ablation therapy (placing a probe or needle into the tumor to kill the cells), targeted therapy (drugs that interfere with substances needed for cancer to grow), immunotherapy (treatment that uses the immune system or products of the immune system to fight cancer), resection surgery, or liver transplant.

Prevention

Diabetes and liver disease are not always avoidable since the underlying causes can vary. For instance, type 1 diabetes (the autoimmune form of diabetes) is largely influenced by genetics and other factors that are not readily modifiable. Similarly, there are autoimmune forms of liver disease that are poorly understood and not easily prevented.

With that said, many of the causes of type 2 diabetes and CLD are well-known and can be avoided with certain preventive strategies.

Summary

Diabetes and chronic liver disease (CLD) are closely linked. On the one hand, uncontrolled diabetes can cause changes to the liver that can lead to nonalcoholic fatty liver disease, cirrhosis, and liver cancer. On the other, CLD can make liver cells less sensitive to insulin and contribute to the onset of type 2 diabetes. It can be difficult to know which is the cause and which is the effect.

People with diabetes and CLD are treated with a combination of lifestyle changes and medications to better manage blood sugar levels. Managing diabetes places less stress on the liver, preserving its function and slowing disease progression.

A Word From Verywell

One of the challenges of diabetes and chronic liver disease is that both are often asymptomatic (without symptoms), particularly in the early stages. This is especially true for people with CLD. Less than 2% of whom are diagnosed, according to the Centers for Disease Control and Prevention (CDC).

To this end, it is important to know and recognize the early signs of liver disease—including fatigue, nausea or vomiting, dark urine, pale stools, and jaundice (yellowing of the eyes or skin)—and report them to your healthcare provider immediately so that you can seek treatment and avoid long-term health complications.