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ADA: Screen All With Type 2 Diabetes for Fatty Liver Disease

SAN DIEGO — The American Diabetes Association (ADA) now advises universal screening of people with type 2 diabetes and prediabetes for fatty liver disease and provides new recommendations for management in those with the condition, or who are at risk for it.

Liver disease affects up to 70% of people with type 2 diabetes, and is common in people with prediabetes, and in those with type 1 diabetes who also have obesity. Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in people with diabetes. It can lead to cirrhosis and liver cancer and is associated with an increased risk for cardiovascular disease and death. The condition includes non-alcoholic steatohepatitis (NASH).

“The ADA has recognized that this has become a big problem for their patients because NASH is becoming the number one cause of cirrhosis in people with type 2 diabetes and the number one cause of liver transplantation in the US, so we have to do something about it,” Kenneth Cusi, MD, who presented a summary of the new guidance here at the ADA’s annual Scientific Sessions, told Medscape. 

The new ADA guidance was published June 24 as a mid-year update to the ADA’s Standards of Care in Diabetes—2023 in the section on “Comprehensive Medical Evaluation and Assessment of Comorbidities.”

Asked to comment, Atlanta endocrinologist Scott Isaacs, MD, said “It is wonderful to see that the ADA has recognized NAFLD…as the hepatic complication of type 2 diabetes and has updated the Standards of Care reflecting the current knowledge and evidence of this ubiquitous and often silent disease.”

The new ADA guidance aligns with those of other professional societies, including the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Society, and the American Association of Clinical Endocrinology (AACE).

Isaacs, who chaired the AACE guidance writing panel, noted, “The ADA update essentially repeats the same guidance in the AACE and AASLD documents. It is excellent to see this type of alignment of guidance among the major organizations.”

FIB-4: Easy Calculation in the EHR

The ADA now advises screening all adults with type 2 diabetes or prediabetes, particularly those with obesity or cardiometabolic risk factors or established cardiovascular disease — even those with normal liver enzyme levels. People with type 1 diabetes who have obesity and/or cardiovascular risk factors are also to be screened for NAFLD.

The recommended screening tool is the fibrosis-4 index (FIB-4), a calculation that includes the patient’s age, liver enzyme levels, and platelet counts. A score of 1.3 or higher is considered high risk for clinically significant fibrosis, and above 2.6 is very high-risk.

Cusi noted, “The reason we advise using the FIB-4…instead of liver enzymes as ADA advised in the past, is that now we know that 70% of people with type 2 diabetes have steatosis already and about one in five have fibrosis, but if you go by liver enzymes you will miss most of them. Liver enzymes are ineffective as a screening tool.”

The FIB-4 is “a simple tool we already have in our electronic health records (EHR) but we’re just simply not using it,” noted Cusi, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville. 

Indeed, Isaacs said, “The FIB-4 is a simple…great screening test because it is essentially free.” But he cautioned that it has some limitations.

“It is a good test for ruling out advanced liver disease but can have false positives and false negatives. The FIB-4 cutoffs need to be adjusted for persons over 65 years old and is not to be used for persons under 30 years old.”

Isaacs also pointed out that, while the calculation can be done from a website, “even this adds time to a clinician’s busy day. Ideally, the FIB-4 should be automatically calculated in the EHR or on the lab report, similar to the [estimated glomerular filtration rate] calculation [for kidney function] and flagged if greater than 1.3.”

The ADA update also provides guidance on follow-up for patients flagged with the FIB-4, including when referral to a gastroenterologist or hepatologist is appropriate.

Treatment: Lifestyle Modification Plus GLP-1 Agonists or Pioglitazone

Lifestyle modification is recommended for all adults with diabetes or prediabetes and NAFLD, particularly those with overweight or obesity.  

In addition, the ADA now advises consideration of a using a glucagon-like peptide 1 (GLP-1) agonist with demonstrated benefits in NAFLD as adjunctive therapy to lifestyle interventions for weight loss in those with type 2 diabetes, particularly with overweight/obesity.

And for those with biopsy-proven NASH or who are identified with clinically significant liver fibrosis using non-invasive tests, either a GLP-1 agonist or pioglitazone are the “preferred treatments.”

However, insulin is the preferred treatment for hyperglycemia in adults with type 2 diabetes who have decompensated cirrhosis.

Isaacs commented, “Pioglitazone has so many benefits and a few known risks…it is an underused medication. It is very inexpensive. Pioglitazone should be considered as a first line treatment for patients with type 2 diabetes and NAFLD.”

The ADA update also advises statin therapy for people with type 2 diabetes and NAFLD, given their increased cardiovascular risk. However, statins are not recommended for people with decompensated cirrhosis because of limited safety and efficacy data.

Cusi noted that he has been advocating for fatty liver screening in people with type 2 diabetes for over a decade.

“Doctors have already been adopting it, but ADA as an organization in diabetes care has a big impact. I dreamed many years ago that the day would come when we would screen all people with type 2 diabetes, and that day is today.”

Cusi is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, BMS, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, Thera Technologies, and MSD. Isaacs reports no relevant financial relationships.

Update to ADA’s Standards of Care. Published June 24, 2023 and presented at the ADA Scientific Sessions.

Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.

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