High Liver Enzyme Levels Linked to Risk of CF-Related Diabetes, Especially in Men, Study Finds

High blood levels of the enzyme alanine aminotransferase (ALT)  — a biomarker of liver damage — might indicate a higher risk of rising blood sugar levels and cystic fibrosis-related diabetes (CFRD), especially in men, a study found.

These data suggest that ALT could serve as a marker of CFRD risk in CF patients, allowing early diagnosis and treatment.

The study, “Hepatic enzyme ALT as a marker of glucose abnormality in men with cystic fibrosis,” was published in the journal PLOS ONE.

People with CF often develop glucose intolerance that can lead to diabetes. Those without CF but with liver diseases, such as fatty liver, are known to be a higher risk of developing type 2 diabetes. A recent study also suggested that liver damage can be associated with diabetes in the CF population.

Researchers in Canada and the U.S. investigated whether high levels of ALT in the blood of CF patients were related to blood sugar levels and CFRD development.

Their study included 273 adults (mean age, 25.7) recruited from the Montreal CF Cohort. None had been diagnosed with CFRD at its beginning.

Participants entering the study were given an oral glucose tolerance test, lab tests to measure liver enzymes, and a medical examination to asses weight, body mass index (BMI; healthy weight is 18.5–24.9), and pancreas and lung function. They were then followed for 1 and 1.5 years, and these tests were repeated.

Results showed that patients with high ALT levels were mostly men (83%), had higher weight and BMI (mean BMI of 23.0 vs. 21.0), lower resistance to glucose, and lower pancreatic function than did those with normal ALT levels. Lung function was similar between these two groups.

Researchers also studied men and women separately because glucose processing varies with sex.

They found that men with high ALT levels had higher weight and BMI (mean, 23.2), lower glucose tolerance and sensitivity to insulin (both of which indicate early stages of diabetes), and a higher risk of being diagnosed with CFRD during the follow-up period (20.5% vs. 8.2%) than did men with normal ALT levels.

Women with high ALT levels tended to have higher BMI and levels of blood sugar, but the differences were not statistically significant. The team noted that this lack of significant difference could be due to either the study’s low numbers of women with high ALT, or to women being naturally more resistant to CFRD.

“Our results revealed that CF patients with higher ALT levels have higher weight and BMI, particularly in men. It is an interesting trend, as previous data have shown a predominance of adult men with CF as being overweight or obese,” the researchers wrote.

Measuring ALT levels might be an easy and inexpensive way of identifying CF patients at risk of developing diabetes, especially among men, they said, ensuring an earlier diagnosis and treatment that can lead to better outcomes.

“This is the first study to describe glycemic variation and insulin sensitivity in relation to ALT levels in a CF population, supporting similarities between the development of CFRD and [type 2 diabetes],” the researchers concluded.

“Additional studies are required to confirm these observations and validate the most appropriate ALT cut-off to use in clinical practice,” the team added.