Hepatic enzyme ALT as a marker of glucose abnormality in men with cystic fibrosis

Abstract

Aim: Cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). In non-CF patients, liver disease, specifically steatosis and non-alcoholic fatty liver disease (NAFLD), is strongly associated with type 2 diabetes. We compared glycemic status and metabolic profiles in CF patients according to a biomarker of hepatic injury, alanine aminotransferase (ALT).

Methods: We conducted a cross-sectional study among 273 adult CF patients recruited from the Montreal CF Cohort. A 2-hour oral glucose tolerance test (OGTT) was performed to collect glucose and insulin measures every 30 minutes. Fasting ALT levels and anthropometric measures were also obtained. Patients were categorized into 2 groups based on ALT cut-off of 25 U/L.

Results: Patients in the high ALT group were mostly men (83%), had higher mean weight and BMI (p<0.001) and showed elevated glucose levels throughout OGTT (p≤0.01). When stratified by sex, only men with high ALT showed significantly higher weight (p<0.001), higher glycemic values at 60, 90 and 120 minutes of OGTT (p≤0.01), higher frequency of de novo CFRD (20.5% vs 8.2%, p = 0.04) as well as lower insulin sensitivity than men with normal ALT (p = 0.03). ALT levels were strongly associated with HOMA-IR in CFRD patients (p = 0.001, r2 = 0.28).

Conclusions: Adult CF men with higher ALT show an increased frequency of dysglycemia and de novo CFRD, lower insulin sensitivity and higher eight. Our data suggests that ALT levels could be an interesting tool to guide targeted diabetes screening, particularly among CF men. Prospective studies are needed to confirm these observations.

Conflict of interest statement

Dr Rabasa-Lhoret received a Grant from Cystic Fibrosis Circle of Care by Vertex. No other authors have any conflicts of interest to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1

Glycemia excursion during OGTT (A) and HbA1c (B) in normal and high ALT groups. Patients in high ALT group demonstrate higher glycemia levels at all OGTT time-points and higher HbA1c. *p ≤ 0.05; ***: p ≤ 0.001.

Fig 2

Glucose (A), insulin sensitivity (B), BMI (C) and fat mass percentage (D) differences between normal and high ALT groups following sex stratification. Men with high ALT have higher glucose levels at T60 to T120 min and show markers of decreased insulin sensitivity compared to men with normal ALT. Men with high ALT have higher BMI and higher percentage of fat body mass than men with normal ALT. No significant differences were observed between the women groups. *: p ≤ 0.05 between men with normal and high ALT; ***: p ≤ 0.001 between men with normal and high ALT; $: p ≤ 0.05 between men and women with normal ALT; $ $ $: p ≤ 0.001 between men and women with normal ALT; ¥: p ≤ 0.05 between men and women with high ALT; ¥¥¥: p ≤ 0.001 between men and women with high ALT.