Type 2 diabetes and liver disease: How they’re connected

People with Type 2 diabetes are at high risk of developing liver disease — and they should be screened for it even if no symptoms of liver disease are present, said Mary E. Rinella, MD, a University of Chicago Medicine transplant hepatologist.

The opposite effect also can occur: Liver disease could lead to the development of Type 2 diabetes, according to recent studies that highlight connections between the two diseases.

Still, awareness of the link between diabetes and liver disease “remains really low," said Rinella, who is also director of the Metabolic Liver Clinic at UChicago Medicine.

Type 2 diabetes can be diagnosed with a simple blood test. “You really want to get on top of it early,” Rinella said. “What we can all do is try to prevent the progression of disease that’s sitting right under our noses.”

It’s why Rinella recently wrote recommendations for the American Association for the Study of Liver Diseases (AASLD) that advise FIB-4 testing for any person with diabetes.

FIB-4 is a calculation based on routine blood tests used to screen for metabolic dysfunction-associated steatotic liver disease (MASLD) — formerly known as nonalcoholic fatty liver disease — which affects seven in 10 people with Type 2 diabetes.

How Type 2 diabetes worsens liver disease

One of the main functions of the liver is to maintain healthy blood sugar levels. Insulin, a hormone made by the pancreas, acts as a messenger to alert cells to take up glucose from the blood.

But in a liver damaged by fat deposits, scarring or cirrhosis, those cells become less responsive to insulin’s signals. The pancreas reacts by releasing more insulin until it can no longer keep up.

This insulin resistance is the foundation of Type 2 diabetes, which worsens liver disease in a spiral that can progress unnoticed until the appearance of symptoms such as jaundice, fatigue, gastrointestinal bleeding, abdominal swelling or confusion.

“Most of the patients that have liver disease, even advanced cases, are not diagnosed,” Rinella said. “By the time you have symptoms, things are often too advanced to reverse.”

Early testing and intervention are critical. The development of cirrhosis is the most common reason to need a liver transplant, said Rinella, who also coauthored practice guidelines issued in 2023 by the AASLD and American Association of Clinical Endocrinology.

“If you were able to identify liver disease early — say, when you just had MASLD without severe scarring — you could prevent it altogether so you never have to worry about cirrhosis, liver cancer or transplant,” she said.

Preventive care and medications to know

Exercise and a diet low in carbohydrates and saturated fats can promote weight loss and help improve insulin sensitivity in the body, a benefit to patients with liver disease and/or diabetes.

Many people successfully make changes with guided support, according to Sarah Vilt, MS, RD, LDN, a registered dietitian at UChicago Medicine who helps patients with MASLD move from small lifestyle modifications to their ultimate goal.

“Seven to 10 percent of total body weight loss needs to be achieved to stop the progression of liver disease,” Vilt said.

Semaglutide, the active ingredient found in Ozempic, Wegovy and Rybelsus, can be prescribed to help some patients lose weight. Bariatric surgery also is an option, Rinella said.

She anticipates the U.S. Food and Drug Administration will soon approve the drug resmetirom. It would be the first drug for treating metabolic dysfunction-associated steatohepatitis, or MASH, a more advanced stage of MASLD characterized by liver inflammation and scarring.

Other options could be on the horizon, Rinella said. Tirzepatide, branded as Mounjaro, significantly reduced liver fat in patients in a recent study, and the experimental drug retatrutide shows promise in stopping the progression of liver disease — and possibly reversing it.