Longitudinal Change In Liver Aminotransferase Predicts Metabolic Syndrome-A Health Check-up Cohort Based Study

BackgroundMetabolic syndrome (MS), defined by a constellation of metabolic disorders (hypertension, hyperlipidemia, obesity and hyperglycemia), has been shown to be an important risk factor for cardiovascular disease and all-cause mortality. In recent decades, as a result of spread of western lifestyle and increase in life expectancy, the prevalence of MS in China is dramatically increasing. According to Liu Xiaomeng’s survey on residents aged from 18-69 years old in Shandong Province, the prevalence of MS were 17.67%. It is very important to prevent and control MS at the early stage through targeted measures for different groups in China.The prevalence of MS is rapidly increasing worldwide, largely as a consequence of the ongoing obesity epidemic, which may be due to insulin resistance (IR). IR would induce excessive burden on mitochondria, nucleus and endoplasmic reticulum, which may lead over accumulation of viscera adipose tissue and finally associated with incidence of non-alcoholic fatty liver disease (NAFLD). Therefore, NAFLD might be hepatic expression of MS at the early stage. Some epidemiological studies used increasing levels of serum liver aminotransferase (including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as surrogate markers for nonalcoholic fatty liver disease (NAFLD). Besides, it was found that increasing liver aminotransferases were associated with vascular endothelial disorders, body insulin sensitivity and type 2 diabetes. Therefore, serum liver aminotransferase may be biomarkers for MS in individuals.To date, many studies that used cross-sectional studies could not solidly determine the association of serum ALT and AST with the incidence of MS. Further, although levels of AST and ALT may vary over time, exiting cohort studies ignored changes of serum ALT and AST during the follow-up and only analyzed the associations between baseline levels of ALT and AST and the incidence of MS. Therefore, it has not determined that whether high serum levels of ALT and AST are associated with incident MS.Objectives1. To clarify the relationship between serum ALT/AST and the incidence of MS in males and females.2. To explore the relationship between serum ALT/AST and MS’s components/NAFLD in males and females.MethodsA dynamic health examination cohort study was set at a general hospital in Dongying City, China, from January 2006 to December 2011. The criterion given by Chinese Medical Association Diabetes Branch (CDS) was adopted to define MS in the study. General statistical analysis of the data and multivariate analysis for the generalized estimated equation model (GEE) were performed by SAS 9.1. Simple GEE model was first used to select factors associated with MS, and multiple GEE model was further adopted to detect the association between ALT/AST and MS. Variables which were significant at the level of 0.10 (a) in the simple GEE analysis and were satisfied with clinical values entered the multiple GEE model to adjust potential confounding factors. Age was regarded as the underlying timescale. Instead of analyzing baseline variables like former cohorts, the GEE model analyzed repeated observations of both aminotransferases and potential covariates from baseline to follow-ups. Serum ALT and AST levels were divided into quartiles and the lowest category was used as the referent in analyses. The GEE models used’Logit’as the link function, and P<0.05 was considered significant.Results1. The general information of the individuals:4541 individuals were included in this study,2904 males and 1637 females.710 participants developed MS during the follow-ups, and the incidence density was 6.16 per 100 person-year.2. Simple and multiple GEE analysis of ALT and AST (in quartiles) and MS in males and females:2 models were taken in the GEE analysis including a crude model and a multivariate (including age, GGT, TBIL, T-CH, smoking and drinking) adjusted model. With increasing ALT and AST grading, the crude RR and multivariate RRs for MS increased in a dose dependent manner from second quartile to fourth quartile (P<0.001). The RRs of ALT for MS were more effective than AST for MS.3. Simple and multiple GEE analysis of ALT and AST (in quartiles) and MS’s components/fatty liver diseases:In both males and females, increasing ALT levels was positively correlated with hyperlipidemia, obesity and fatty liver diseases in a dose dependent manner (P<0.001). And AST was positively correlated with hypertension, hyperlipidemia, obesity, hyperglycemia and fatty liver diseases in both males and females with a dose dependent manner (P<0.001). The positive associations between serum ALT/AST and fatty liver were significant, and the association between high ALT and fatty liver were much stronger than that for high AST especially in males.4. Simple and multiple GEE analysis of ALT/AST (in quartiles) and MS in subgroup of participants with different metabolic conditions:the positive association between ALT/AST and MS were consistently observed among the following subgroups:ALT less than 40U/L in baseline, AST less than 40U/L in baseline, BMI<25 kg/m2 in baseline, and non-fatty liver in baseline.Conclusions1. Elevated serum ALT and AST are biomarkers for the incidence of MS.2. The positive association between serum ALT and fatty liver disease is closer than it between serum AST and fatty liver disease.3. Even in participants with normal serum ALT level, normal serum AST, healthy body form or having no fatty liver, elevated serum ALT and AST are still risky biomarkers of incident MS.