Abstract
Elevated concentrations of liver enzymes have been associated with an increased risk of developing type 2 diabetes mellitus. However, it remains unclear to which specific aspects of diurnal glucose metabolism these associate most. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts. This cross-sectional study included 436 participants without diabetes mellitus from the Active and Healthy Aging Study, the Switchbox Study, and the Growing Old Together Study. Fasting blood samples were drawn to measure gamma-glutamyltransferase (GGT), alanine transaminase, and aspartate transaminase. Measures of glycemia (e.g., nocturnal and diurnal mean glucose levels) and glycemic variability (e.g., mean amplitude of glucose excursions) were derived from continuous glucose monitoring. Analyses were performed separately for the three cohorts; derived estimates were additionally meta-analyzed. After meta-analyses of the three cohorts, elevated liver enzyme concentrations, and specifically elevated GGT concentrations, were associated with higher glycemia. More specific, participants in the highest GGT tertile (GGT ≥37.9 U/L) had a 0.39 mmol/L (95% confidence interval: 0.23, 0.56) higher mean nocturnal glucose (3:00 to 6:00 a.m.) and a 0.23 mmol/L (0.10, 0.36) higher diurnal glucose (6:00 to 0:00 a.m.) than participants in the lowest GGT tertile (GGT <21.23 U/L). However, elevated liver enzyme concentrations were not associated with a higher glycemic variability. Though elevated liver enzyme concentrations did not associate with higher glycemic variability in participants without diabetes mellitus, specifically, elevated GGT concentrations associated with higher glycemia.
Highlights
It has been well recognized that the prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide [1, 2]
We aimed to investigate the associations between liver enzyme concentrations and measures of glycemia and glycemic variability in a cross-sectional study comprising middle-aged individuals without T2DM
The results of the present study provided evidence that, using data from three independent studies, elevated liver enzyme concentrations, and elevated GGT concentrations, were associated with higher glycemia during day and night
Summary
It has been well recognized that the prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide [1, 2]. Disease conditions as non-alcoholic fatty liver disease (NAFLD) or a preclinical higher degree of liver adiposity have been described to increase the risk of T2DM [5,6,7]. There are still limited data available on the association between elevated liver enzyme concentrations and the dynamic aspects of glucose metabolism over 24 h, like glycemia and glycemic variability. Such insights will provide additional information about the pathophysiological mechanisms in which elevated liver enzyme concentrations are involved. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts
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