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, r 2 = 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.

A High De Ritis Ratio is Associated with Mortality in Adult Trauma Patients

“…36 Notably, AST and ALT play important roles in carbohydrate and protein metabolism, which is a component of the malate-aspartate shuttle pathway that allows NADH/NAD+ conversion 2 and is involved in aerobic glycolysis, whereas ALT plays a crucial role in the glucose-alanine cycle to produce glucose to meet glucose requirements. 5 Due to the fact that AST and ALT activate nucleotides and non-essential amino acids engaged in aerobic glycolysis and boost glutamine metabolism in growing cancer cells, [37][38][39][40] the De Ritis ratio is associated with tumor metabolism in numerous tumors that utilize glucose. 41 Therefore, we propose that an increased De Ritis ratio represents the need for glucose intake in trauma patients experiencing stress.…”

Delta De Ritis Ratio Is Associated with Worse Mortality Outcomes in Adult Trauma Patients with Moderate-to-Severe Traumatic Brain Injuries

“…Aspartate aminotransferase and ALT catalyze nucleotide and nonessential amino acids involved in aerobic glycolysis, and function as important links between protein and carbohydrate metabolism [ 36 , 37 , 38 ]. In contrast to the role of ALT in the glucose-alanine cycle to produce glucose to cope with sugar consumption [ 9 ], AST plays a vital role in the malate–aspartate shuttle pathway involved in aerobic glycolysis, which allows conversion between NADH and NAD+ [ 39 ].…”

Using Second Measurement of De Ritis Ratio to Improve Mortality Prediction in Adult Trauma Patients in Intensive Care Unit

“…In addition, the elevated DRR was mainly attributed to an elevated AST level in the second measurement of the death patients. Notably, although both AST and ALT are involved in aerobic glycolysis, catalyzing nucleotide and nonessential amino acids [ 46 , 47 , 48 ], an isolated elevation of AST values indicates a non-hepatic source of AST from the injury to non-liver cells, particularly those cells containing mitochondria [ 3 ]. Elevated AST levels, but not ALT, led to a higher DRR and indicated mitochondrial dysfunction upon oxidative stress [ 3 , 49 , 50 ].…”