Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

• Published in: Diabetic medicine Vol. 33; no. 3; pp. 356 - 364
• Main Authors: Williams, K. H., Sullivan, D. R., Veillard, A. S., O'Brien, R., George, J., Jenkins, A. J., Young, S., Ehnholm, C., Duffield, A., Twigg, S. M., Keech, A. C.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2016; Wiley Subscription Services, Inc
• Subjects: Adipose tissue; Adult; Aged; Alanine; Alanine transaminase; Alanine Transaminase - blood; Biomarkers - blood; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Cerebral infarction; Death; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Enzymes; Fatty liver; Female; Fenofibrate; Fenofibrate - therapeutic use; Frailty; gamma-Glutamyltransferase - blood; Health risk assessment; Humans; Incidence; Insulin; Liver diseases; Male; Metabolic syndrome; Middle Aged; Myocardial infarction; Risk Factors; Risk groups; Stroke; γ-Glutamyltransferase
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.12972

Aims To determine whether alanine aminotransferase or gamma‐glutamyltransferase levels, as markers of liver health and non‐alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non‐fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. Results Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4–13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8–41 U/l for women and 9–59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12–3.09) and 0.65 (95% CI 0.49–0.87), respectively (P = 0.001). No relationship was found for gamma‐glutamyltransferase. Conclusions The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non‐alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health. What's new? Alanine aminotransferase and gamma‐glutamyltransferase are associated with measures of adiposity, metabolic syndrome, insulin resistance and poorer glycaemic control in people with Type 2 diabetes. Lower alanine aminotransferase but not gamma‐glutamyltransferase levels predict a higher risk of a cardiovascular event over time and, as such, may be a marker of systemic or hepatic frailty in people with Type 2 diabetes, rather than liver health and absence of non‐alcoholic fatty liver disease. The study highlights the fact that further study is needed into the mechanisms by which lower alanine aminotransferase levels are associated with adverse cardiovascular outcomes in various at‐risk groups, with a particular emphasis on formal assessment of comorbidity, biological frailty, non‐alcoholic fatty liver disease severity and lipid variables.