Quartiles Of Alanine Aminotransferase Research Articles

Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study

Emerging data suggest that an increase in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as biomarkers of oxidative stress are associated with increased risk of impaired fasting glucose (IFG). The present study was an investigation of whether an increase in serum ALT and GGT had a combined effect on increasing IFG risk through cross-sectional and longitudinal studies. In the cross-sectional study, data were analyzed from 9937 subjects without diabetes who underwent health check-ups between 1999 and 2001 (baseline data). In the longitudinal study, 6390 subjects were analyzed who had been rechecked between 2009 and 2014, excluding IFG patients from baseline data. In cross-sectional analysis, adjusted odds ratio (OR) of IFG in the fourth quartile of both ALT and GGT was 1.829 (95% confidence interval [CI] 1.545–2.164) compared with the reference group (1st and 2nd quartiles of ALT and GGT). In longitudinal analysis, IFG probability increased gradually with an increase in the circulating levels of ALT and GGT. Adjusted hazard ratios for developing IFG in the fourth quartile of both ALT and GGT was 1.625 (95% CI 1.263–2.091) compared with the reference group (1st and 2nd quartiles). Increased serum ALT and GGT levels are well associated with IFG after potential confounders are adjusted for, and elevated ALT and GGT at the same time can have a combined effect in predicting the development of IFG.

First-phase insulin secretion is positively correlated with alanine aminotransferase in young adults.

Type 2 diabetes (T2D) is known to be one of the most prevalent diseases, and its prevalence is significantly associated with age and metabolic syndrome (MetS). Few studies have been conducted on liver function, MetS and insulin secretion among young adults. In the present study, we explored the relationship between the liver function enzyme - alanine aminotransferase (ALT) - and first-phase insulin secretion (FPIS) among young adults. There were 22,971 men and 28,740 women, aged 18-27 years, assigned to subgroups according to the presence of MetS and quartiles of ALT values. Simple correlation was applied to evaluate their relationship. The difference between the slopes of these relationships and FPIS were statistically analyzed with Chris's calculator. Most values for metabolic parameters, including ALT and FPIS, were determined to be relatively high in individuals with MetS. By contrast, individuals with MetS had lower high-density-lipoprotein cholesterol (HDL-C) counts and FPIS. Similar results were observed in the quartiles of ALT. Significant positive results were also found in the linear model. Depending on the ALT level, the slope change of FPIS still demonstrated a positive correlation between ALT and FPIS. This correlation was stronger for men than for women. A positive correlation between ALT and FPIS exists among young adults. Moreover, this correlation was stronger for men than for women. Both the cause and the effect require further investigation.

Association of liver enzymes with incident diabetes in US Hispanic/Latino adults.

Non-alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD. We conducted a prospective cohort study of 6,928 adults of Hispanic/Latino background who had no diabetes, did not report excessive alcohol use, and no hepatitis B and C infection at baseline (2008-2011). We estimated risk ratios (RR) for incident diabetes, identified from visit 2 examination by glucose measurements or antidiabetic medication use, with baseline liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)). A total of 738 adults developed diabetes during 6years of follow-up. After adjusting for participant characteristics at baseline, versus the lowest quartile, highest quartiles of ALT and GGT were associated with risks for incident diabetes (RR for ALT: 1.51 [95% CI 1.03-2.22], p-trend=0.006; RR for GGT: 2.39 [1.60-3.55], p-trend=0.001). Higher GGT levels predicted increased risk of incident diabetes even among those with ALT or AST below the median levels. The associations of ALT and GGT with incident diabetes were similar among most Hispanic background but were not seen among Dominicans (p for interaction <0.05). The association of AST with incident diabetes was found only among light-to-moderate alcohol drinkers (RR=1.50 [1.20-1.86]) but not abstainers (RR=0.91 [0.69-1.20], p for interaction=0.006). Higher ALT and GGT levels are associated with increased risk of developing diabetes among Latinos. Liver enzyme tests might aid in diabetes prevention by identifying high-risk individuals.

Association of Alanine Aminotransferase With Different Metabolic Phenotypes of Obesity in Children and Adolescents: The CASPIAN-V Study.

Aim: To determine the association of alanine aminotransferase with different metabolic phenotypes of obesity in a nationally- representative sample of Iranian children and adolescents.Methods: This national study was conducted in the framework of the fifth survey of a national surveillance program entitled Childhood and Adolescence Surveillance and Prevention of Adult Non-communicable Disease study. Participants consisted of 4,200 subjects aged 7–18 years, who were recruited by multistage random cluster sampling from 30 provinces in Iran. They were categorized to normal weight and obese groups and in each group those with and without MetS components.Results: Overall, 3,843 of participants completed the survey (response rate: 91.5%). Their mean (SD) age was 12.58 (3.15) years; 52.6% were boys, and 72.7% lived in urban areas. Mean of alanine aminotransferase (ALT) in subjects with abdominal obesity and general obesity was 8.81 (95% CI: 7.99–9.62) (IU/L) and 8.87 (95% CI: 7.28–10.46) (IU/L), respectively. According to the adjusted model, one unit increment in ALT increased odds of being metabolically non-healthy obese (MNHO) by 2% compared to metabolically healthy non-obese (MHNO) [adj.OR (95% CI): 1.02 (1.01–1.04)]. Also, subjects in the third and fourth quartiles of serum ALT had significantly greater odds of being MNHO than those in its first quartile [Q3/Q1: adj. OR (95% CI): 3.85 (1.70–8.71); Q4/Q1: Adj. OR (95% CI): 3.63 (1.51–8.73)].Conclusion: This large population-based study revealed significant associations between metabolic phenotypes of obesity and ALT level.

The Associations between Liver Enzymes and Cardiovascular Risk Factors in Adults with Mild Dyslipidemia.

Hypertension and dyslipidemia often occur as comorbidities, with both being strong risk factors for developing cardiovascular diseases (CVD). Abnormal liver function test could reflect a potential CVD risk even in patients with mild dyslipidemia. The aim of this study was to assess the compounding relationship between liver enzymes and cardiovascular risk factors in subjects with mild dyslipidemia. The present analysis was performed among 438 participants who had enrolled in at least one of the nine clinical studies done at the Chonbuk National University Hospital between 2009 and 2019. Significant linear increasing trends were observed in blood pressure level and other cardiovascular risk factors across quartiles of serum γ-glutamyltransferase (GGT) or alanine aminotransferase (ALT), with the increment in hypertension prevalence occurring across the quartiles of GGT and ALT. On multivariate logistic regression analyses, the odds ratios for hypertension, adjusted for smoking, drinking and obesity, in the highest quartiles of GGT, ALT, aspartate aminotransferase, and alkaline phosphatase were 3.688, 1.617, 1.372, and 1.166, respectively. Our study indicates that GGT is a superior marker for predicting CVD risk among liver enzymes. Routine screening of plasma GGT levels in patients with mild dyslipidemia will allow for early detection of CVD.

Combined effect of serum alanine aminotransferase and gamma-glutamyltransferase on incidence of diabetes mellitus: A longitudinal study.

High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26–2.83, P = .002) and 3.526 (95% CI: 2.12–5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42–5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.

Low alanine aminotransferase levels predict low muscle strength in older patients with diabetes: A nationwide cross-sectional study in Korea.

Low alanine aminotransferase (ALT) level is associated with frailty in the older adult population. We investigated the usefulness of ALT in predicting low muscle strength among older patients with diabetes. We included 550 men aged ≥50 years and 525 postmenopausal women. All participants had diabetes, and data were based on the 2014-2016 Korea National Health and Nutrition Examination Survey. Participants with ALT levels confounded by hepatic causes or who had a cerebrovascular accident were excluded. The accompanying metabolic disorders and the associated parameters were evaluated. Low muscle strength was defined as handgrip strength below the Korean-specific cut-off value. In men and women, when ALT level was divided into quartiles (Q1-Q4), a positive correlation between ALT and body mass index, triglycerides, fasting plasma glucose, glycated hemoglobin levels and handgrip strength was observed, whereas a negative correlation was observed with age and duration of diabetes (P < 0.05, all). After adjusting for age, sex, protein intake, aerobic exercise, body mass index, duration of diabetes, glycated hemoglobin and triglycerides, the lower ALT quartiles ([Q1 and Q2) showed a higher risk for low muscle strength compared with Q4 (OR 2.123 and 2.437; P = 0.060 and 0.029). The cut-off ALT level for low muscle strength was 18.5 IU/L. Older patients with diabetes with ALT levels below low-to-normal should not be considered metabolically healthy. Clinicians should pay special attention to the risk of low muscle strength in individuals with ALT levels of ≤18.5 IU/L, independent of any associated metabolic disorders. Geriatr Gerontol Int 2020; 20: 271-276.

Utility of ALT Concentration in Men and Women with Nonalcoholic Fatty Liver Disease: Cohort Study.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT), but the clinical utility of ALT in detecting and following individuals with NAFLD remains unclear. We conducted a retrospective analysis of 30,988 men and 5204 women with NAFLD diagnosed by ultrasound and stratified them according to sex-specific ALT quartiles. We compared metabolic variables at baseline and repeated ultrasound after at least 6 months among ALT quartiles (Q) in men (Q1 5–24, Q2 25–33, Q3 34–48, Q4 ≥ 49 IU/L) and women (Q1 5–14, Q2 15–20, Q3 21–28, Q4 ≥ 29 IU/L). Prevalence of obesity (BMI ≥ 25 kg/m2) and metabolic abnormalities (glucose intolerance, hypertension) significantly (p < 0.001) increased from ALT Q1 to Q4 in both men and women at baseline. After a mean follow-up of 4.93 years, 17.6% of men and 31.1% of women resolved their NAFLD. The odds ratio (OR) of resolving significantly (p < 0.001) decreased by quartiles even after multiple adjustments. The adjusted OR for resolution in Q4 was 0.20 (0.18–0.23) in men and 0.35 (0.26–0.47) in women compared with Q1. Individuals with NAFLD span the full range of ALT concentrations, but those with the highest ALT have the worst metabolic profile and persistent NAFLD.

Abstract P072: Elevated Liver Enzymes Are Associated With Incident Diabetes in Hispanic/Latino Adults: Results From HCHS/SOL

Introduction: Non-alcoholic fatty liver disease (NAFLD) as measured by ultrasonography or elevated liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD. Methods: We conducted a prospective cohort study of 6928 adults of Hispanic/Latino background who had no diabetes at baseline (2008-2011). Incident diabetes was defined by self-reported diagnosis of diabetes, glucose measurements or antidiabetic medication use at repeat visits on average 6 years from baseline. We examined the associations of baseline liver enzymes (sex-specific quartiles of ALT, AST, GGT) with incident diabetes using survey-weighted Poisson regression with follow-up time as an offset. Results: The weighted mean age was 38 years at baseline. A total of 793 adults developed diabetes during 6 years of follow-up. After adjusting for demographics and socioeconomic status, versus the lowest quartile, highest quartiles of ALT, AST and GGT were significantly associated with 1.5 to 3.5-fold increased risk of incident diabetes. Further adjusting for behavioral variables including diet and exercise, cardiovascular risk factors and cardiovascular medication use, the associations were attenuated and remained statistically significant for ALT (RR quartile 4 vs 1: 1.42[95% CI 1.07-1.90], P-trend=0.001) and GGT (RR quartile 4 vs 1: 1.97[1.34-2.88], P-trend&lt;0.001) but not AST (RR quartile 4 vs 1: 1.28[0.96-1.70], P-trend=0.02). Adjusting for HOMA-IR further attenuated the associations, and GGT but not ALT remained significantly associated with incident diabetes. Conclusion: Elevated ALT and GGT levels are associated with increased risk of developing diabetes among Hispanics/Latinos. Additional work is needed to understand the relationship between NAFLD and diabetes risk in this population.

The associations between liver enzymes and the risk of metabolic syndrome in the elderly

BackgroundStudies have demonstrated that liver enzymes are associated with metabolic syndrome (MetS). However, little information is available regarding these relationships in elderly populations. Our present study aimed to explore the associations between liver enzymes and the risk of MetS in elderly populations. MethodsThis cross-sectional study included 1444 elder participants (970 men and 474 women) who attended annual physical examinations. Univariate and multivariate logistic regressions were performed to estimate the associations between liver enzymes and the risk of MetS and its components according to quartiles of the concentration of each liver enzyme. ResultsThe prevalence of MetS and its components increased remarkably with increasing quartiles of alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) but not with aspartate aminotransferase (AST) in the elderly. Compared with subjects in the bottom quartile, the adjusted odds ratio for MetS in the highest ALT, GGT and ALP quartiles were 1.78 (95% CI 1.21–2.61), 2.58 (95% CI 1.77–3.78) and 1.85 (95%CI 1.27–2.70) respectively. No statistically significant increases in the odds ratio for MetS according to increased quartiles of AST were found in either the univariate or multivariate logistic regression analyses. ConclusionsElevated liver enzymes levels (mainly ALT, GGT and ALP but not AST) are positively associated with the prevalence of MetS in elderly populations.

Infectious mononucleosis and hepatic function.

Abnormal hepatic function is common in infectious mononucleosis (IM). However, it remains unknown why increased transferase levels are more common than bilirubin abnormalities in IM. The current study aimed to investigate these associations in the Chinese population. A total of 95 patients with IM (47 males and 48 females) were enrolled in the current study, as well as 95 healthy controls. Patients were sorted by sex. A receiver operating characteristic (ROC) curve was used to determine cut-off values for IM diagnosis and prediction. Crude and adjusted odds ratios (OR) for IM were analyzed using binary logistic regression. It was determined that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) levels were significantly higher in patients with IM compared with controls; however, total bilirubin (TB) levels were significantly lower in patients with IM. ROCs demonstrated that, if ALT, AST and GGT concentrations were higher than, or if TB was lower than, cut-off values, they were predictive of IM. Binary logistic regression identified that the risk of IM in patients exhibiting high levels of transferases was significantly increased, particularly in males. Crude ORs in ALT quartile 4 were 21.667 and 10.111 for males and females, respectively and adjusted ORs were 38.054 and 9.882, respectively. A significant IM risk of IM was evident in patients with low bilirubin levels and females appeared to be particularly susceptible. For example, crude ORs in quartile 1 were 8.229 and 8.257 for males and females, respectively and adjusted ORs were 8.883 and 10.048, respectively. Therefore, the current study identified a positive association between transferase levels and IM and a negative association between TB and IM. Therefore, the results of the current study indicate that high transferases are suggestive of IM, particularly in males, whereas low TB is suggestive for IM, particularly in females.

Is within-normal range liver enzymes associated with metabolic syndrome in adults?

Considering the clear association between metabolic syndrome and future cardiovascular disease, early detection of metabolic syndrome is important. This study was conducted to assess the correlation between metabolic syndrome components and within-normal-range of liver enzymes in Iranian adults. This cross-sectional study was comprised of 700 Iranian adults in the districts of East Azerbaijan-Iran in 2015. The levels of lipid profile and glucose were measured by enzymatic colorimetric methods. Weight, height, waist circumferences were measured with standard protocols. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) were assessed using the ultraviolet method. The Pearson correlation and Logistic regression were used to for statistical analysis. With increasing the number of metabolic abnormalities, the mean ALT level was increased significantly (Ptrend=0.04). In women, the increase in AST and ALT with increasing the number of metabolic abnormalities was statistically significant (PAST=0.01; PALT<0.001). In men, ALT level had significantly positive correlation with waist circumference (r=0.14, P<0.05), serum TG (r=0.16, P<0.05) and fasting plasma glucose (r=0.17, P<0.01). In women, there was a significant correlation between AST level and serum TG (r=0.15, P<0.05). A significant positive and negative correlation were found respectively between serum ALT and AST/ALT ratio and waist circumference, serum TG and fasting blood glucose. Women in the 4th quartile of ALT were 4.43 fold at an increased risk for metabolic syndrome outcome when compared to those in the first quartile [OR (95% CI): 4.43 (1.69, 11.63)]. In women, with increasing the quartiles of ALT within normal limits, the percent of participants with metabolic syndrome also increased significantly (Ptrend=0.04). Based on the results, the use of ALT and AST:ALT ratio as continuous biomarkers for early signaling of dysmetabolism especially in women could be encouraged.

Association between liver function and metabolic syndrome in Chinese men and women

Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS.

The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease

BackgroundThe triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. We aimed to investigate the ability of TyG, through comparing with the predictive value of alanine aminotransferase (ALT), to identify individuals at risk for nonalcoholic fatty liver disease (NAFLD).MethodsA cross-sectional study was conducted in a Chinese health examination cohort of 10 761 people aged above 20 years. NAFLD was diagnosed by ultrasonography.ResultsCompared with the participants in the lowest quartile of TyG, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 1.8 (1.5–2.1), 3.0 (2.5–3.5), and 6.3 (5.3–7.5) for those in the second, the third, and the fourth quartile of TyG, whereas the corresponding ORs (95% CI) for NAFLD were 1.5 (1.3–1.7), 1.9 (1.6–2.2), and 3.1 (2.6–3.7) for the upper three quartiles of ALT. These results suggested that TyG was superior to ALT in association with NAFLD risk. According to the ROC analysis, the optimal cut-off point of TyG for NAFLD was 8.5 and the area under the ROC curve (AUC) was 0.782 (95% CI 0.773–0.790), with 72.2 and 70.5% sensitivity and specificity, respectively. The AUC of TyG was larger than that of ALT (0.715 (95% CI 0.705–0.725), P for difference <0.0001), whereas the largest AUC was obtained when adding TyG to ALT (0.804 (95% CI 0.795–0.812), P for difference <0.0001).ConclusionsTyG is effective to identify individuals at risk for NAFLD. A TyG threshold of 8.5 was highly sensitive for detecting NAFLD subjects and may be suitable as a diagnostic criterion for NAFLD in Chinese adults.

Metabolic Syndrome and Serum Liver Enzymes in the General Chinese Population.

Background: The aim of this study was to evaluate the associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with metabolic syndrome (MetS) in the general Chinese population. Methods: This study was a multicenter, cross-sectional study which was conducted in rural areas of China from the 2012 to 2013 Northeast China Rural Cardiovascular Health Study (NCRCHS), and 11,573 adults with complete data were included in our final analysis. Elevated ALT and AST levels were defined as >40 U/L. Serum ALT and AST levels within the reference range were divided into quartiles, and their associations with MetS were evaluated by logistic regressions. Results: A total of 7.4% and 3.5% participants had elevated serum ALT and AST levels, respectively. The prevalence of MetS was 37.3% in males and 45.8% in females. After adjusting for potential confounders, we found ALT level elevation, even within the reference range, was independently associated with MetS. The odds ratio (OR) values of MetS in the ALT quartiles 2–4 groups within the reference range were 1.113 (95% CI: 1.019–1.280), 1.375 (95% CI: 1.212–1.560), 1.878 (95% CI: 1.650–2.138) compared with the ALT quartile 1 group, and OR in the elevated ALT group was 3.020 (95% CI: 2.496–3.653). Positive relationship for MetS was also observed in elevated AST group (OR: 1.689, 95% CI: 1.314–2.171), but within the reference range, the AST level was not associated with MetS. Conclusions: Serum ALT level, even within the reference range, was significantly associated with MetS. However, only elevated AST levels above 40 U/L was positively associated with MetS. Within the reference range, we did not find a relationship between AST levels and MetS.

Increased liver markers are associated with higher risk of type 2 diabetes.

To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG). A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers. The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829-5.622, P < 0.001) in men and 4.60 (95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG. Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG.

Serum alanine aminotransferase predicts interventricular septum thickness and left ventricular mass in patients with nonalcoholic fatty liver disease

Alanine aminotransferase (ALT) is a marker of nonalcoholic fatty liver disease (NAFLD) and predicts type 2 diabetes mellitus (DM2) as well as coronary events independently of traditional risk factors and the features of the metabolic syndrome. The extent to which interventricular septum thickness (IVS) and left ventricular mass (LVM) are associated with ALT levels in cohorts of individuals with body weights ranging from overweight to morbid obesity and NAFLD remains still unknown. This was a cross-sectional pilot study involving 151 young White participants with liver ultrasound-proven NAFLD. Standard echocardiograms were used to define LVM, IVS, and left ventricle diastolic function [mitral inflow velocity pattern (E/A ratio) and mitral annulus velocity by tissue Doppler imaging (Em/Am ratio)]. Participants were classified according to ALT quartiles: p25, p50, p75, and p100. The study included 36 men and 115 women with an age of 38.4 ± 0.7 years and BMI of 43.9 ± 0.6 kg/m2. p100 participants disclosed significantly higher homeostasis model assessment (P=0.003), DM2 (P=0.002), and hypertension (P=0.01) prevalence, whereas LVM, IVS, E/A, and Em/Am ratios were significantly higher in this group when compared with their p25 peers (P<0.01). IVS's and LVM's variance were significantly predicted by the statistical models including ALT independently of BMI, hypertension, and DM2. ALT levels predict both IVS and LVM in NAFLD individuals irrespective of their BMI, DM2, hypertension, age, and sex. ALT levels behave as a surrogate marker of left ventricular hypertrophy in overweight and/or obese NAFLD patients. Hence, it seems worth obtaining cardiac ultrasounds in NAFLD patients with elevated ALT levels.

Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study

To examine the associations of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase(AST), and gamma-glutamyl transferase (GGT) with diabetes risk and to determine whether associations differ by race and/or gender. We hypothesized that all liver enzymes would be associated with diabetes risk and that associations would differ by race and gender. Prospective cohort of 7495 white and 1842 black participants without diabetes in the Atherosclerosis Risk in Communities Study. Poisson and Cox models adjusted for demographic, socio-behavioural, and metabolic and health-related factors were used. During a median of 12 years of follow-up, 2182 incident cases of diabetes occurred. Higher liver enzyme levels were independently associated with diabetes risk: adjusted hazard ratios (95% confidence intervals) were 1.68 (1.49-1.89), 1.16 (1.02-1.31) and 1.95 (1.70-2.24) comparing the highest with the lowest quartiles of ALT, AST, and GGT, respectively. Gamma-Glutamyl transferase was most strongly related to diabetes risk, even at levels considered within the normal range (≤ 60 U/l) in clinical practice. Adjusted incidence rates by quartiles of liver enzymes were similar by gender but higher in black versus white participants. Nonetheless, relative associations of ALT, AST, and GGT with diabetes were similar by race (P for interactions > 0.05). Compared with ALT and AST, GGT was more strongly associated with diabetes risk. Our findings suggest that abnormalities in liver enzymes precede the diagnosis of diabetes by many years and that individuals with elevated liver enzymes, even within the normal range as defined in clinical practice, are at high risk for diabetes.

Correlations of serum alanine aminotransferase and insulin resistance, pancreatic B-cell function

To explore the correlations of serum alanine aminotransferase (ALT), insulin resistance and pancreatic B-cell function. A total of 351 first-degree relatives of type 2 diabetes mellitus received a standard oral glucose tolerance test (OGTT) at our outpatient clinic. All subjects were analyzed for the parameters of body mass index (BMI), waist-hip ratio, blood pressure (BP), serum lipids, ALT, aspartate aminotransferase (AST), plasma glucose (PG), true-insulin and proinsulin. Homeostasis model assessment (HOMA) was applied to assess the status of insulin resistance and pancreatic B-cell function. They were divided into 4 groups according to the quartiles of ALT: ALT1 group (< 12.9 U/L), ALT2 group (12.9 - 17.3 U/L), ALT3 group (17.4 - 24.2 U/L) and ALT4 group (≥ 24.2 U/L). The diagnosis of metabolic syndrome was made according to the definition of Chinese Diabetic Society. With the rising serum ALT levels (ALT4 vs ALT1), the levels of BMI [(26.3 ± 2.9) kg/m(2) vs (23.2 ± 3.7) kg/m(2), P < 0.01], HOMA-IR [1.93 (1.21 - 3.26) vs 1.06 (0.65 - 1.54), P < 0.01] and LnHOMA-beta (2.00 ± 0.32 vs 1.87 ± 0.28, P < 0.05) were elevated; BP, serum lipids, PG, true-insulin and proinsulin also increased (P < 0.05 or P < 0.01). The levels of serum ALT [23.3 (16.3 - 37.6) vs 14.3 (10.3 - 18.5) U/L, P < 0.01] and AST [21.5 (18.3 - 32.8) U/L vs 17.9 (15.5 - 22.1) U/L, P < 0.01] increased with the rising number of metabolic disorders (0 vs 3 - 4 metabolic disorders). After adjustments for gender, age, BMI and waist-hip ratio, serum ALT were still positively correlated with BP, serum lipids, PG, fasting true-insulin, 2 h proinsulin, 2 h proinsulin/true-insulin, HOMA-IR and the numbers of metabolic disorder (r = 0.117 - 0.236, P < 0.05 or P < 0.01). After adjustments for gender, age, BMI, waist-hip ratio and HOMA-IR, the serum ALT level remained positively correlated with the numbers of metabolic disorders (r = 0.120, P < 0.05). Multiple stepwise regression analysis showed that triglyceride, HOMA-IR, total cholesterol and 2 h-proinsulin were the independent risk factors for the level of serum ALT (P < 0.05 or P < 0.01). The elevated levels of serum ALT are significantly correlated with metabolic syndrome, insulin resistance and compensatory increases of pancreatic B-cell function. Independently of insulin resistance, the serum ALT level is correlated with metabolic syndrome.

Elevated Liver Function Enzymes Are Related to the Development of Prediabetes and Type 2 Diabetes in Younger Adults

OBJECTIVEElevations in alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT), surrogate markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of metabolic syndrome and related type 2 diabetes. However, information is limited regarding the long-term predictability of ALT and GGT in the development of prediabetes and type 2 diabetes.RESEARCH DESIGN AND METHODSIn this retrospective cohort study, normoglycemic (n = 874), prediabetic (n = 101), and diabetic (n = 80) adults aged 26–50 years (average age 41.3 years) were followed over an average period of 16 years since their young adulthood (aged 18–38 years, average age 25.1 years), with measurements of cardiometabolic risk factor variables including ALT and GGT.RESULTSThe follow-up prevalence rate of adult diabetes status by quartiles of baseline ALT and GGT levels showed an adverse trend for both prediabetes (P < 0.05) and diabetes (P < 0.01). In a longitudinal multivariate logistic regression analysis that included anthropometric, hemodynamic, and metabolic variables, as well as alcohol consumption and smoking, individuals with elevated baseline ALT and GGT levels (per 1-SD increment) were 1.16 and 1.20 times, respectively, more likely to develop diabetes (P = 0.05 for ALT and P < 0.01 for GGT); no such associations were noted for prediabetes. Regarding the predictive value of ALT and GGT, the area under the receiver operating curve analysis yielded C values ranging from 0.70 to 0.82, with values significantly higher for diabetes compared with prediabetes.CONCLUSIONSThese findings in younger adults suggest potential clinical utility of including ALT and GGT as biomarkers in diabetes risk assessment formulations.