Journal List > Korean J Gastroenterol > v.64(4) > 1007285

Choi, Yang, Lee, Byun, Kang, Kim, and Yim: Detailed Distribution of Liver Enzymes according to Gender, Age, and Body Mass Index in Health Checkup Subjects

Abstract

Background/Aims

The aim of this study was to examine the distribution of range of liver enzymes according to age and BMI in each gender using large-scale data.

Methods

Data were gathered from 65,715 subjects who underwent a routine health checkup and did not have HBsAg and anti-HCV. Boxplot analysis was used to examine the distribution of range of liver enzymes according to age and BMI in each gender. Multivariate linear regression analysis was performed for assessment of the association of liver enzymes with age and BMI, and to determine whether the range of liver enzymes was affected by risk factors for metabolic syndrome in each gender.

Results

ALT, AST, and GGT levels showed significant association with BMI in both male and female after adjusting for age. The range of ALT, AST, and GGT levels varied more widely according to the increase in BMI in males than in females, and this finding was more prominent in younger subjects than in older subjects. All risk factors for metabolic syndrome were shown to affect liver enzyme levels in male subjects. However, although most risk factors for metabolic syndrome affected liver enzyme levels, there might be weak or no effect of fasting hyperglycemia on AST, and low serum HDL-cholesterol level on GGT in female subjects.

Conclusions

Age, BMI, and other risk factors for metabolic syndrome had a significant effect on the distribution of range of liver enzymes in each gender, even in this study conducted from Korean health checkup subjects.

References

1. Tiniakos DG. Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: histological diagnostic criteria and scoring systems. Eur J Gastroenterol Hepatol. 2010; 22:643–650.
crossref
2. Targher G, Byrne CD. Clinical review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J Clin Endocrinol Metab. 2013; 98:483–495.
3. Nseir W, Shalata A, Marmor A, Assy N. Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease. Dig Dis Sci. 2011; 56:3439–3449.
crossref
4. Bruckert E, Giral P, Ratziu V, et al. A constellation of cardiovascular risk factors is associated with hepatic enzyme ele-vation in hyperlipidemic patients. Metabolism. 2002; 51:1071–1076.
crossref
5. Bae JC, Cho YK, Lee WY, et al. Impact of nonalcoholic fatty liver disease on insulin resistance in relation to HbA1c levels in non-diabetic subjects. Am J Gastroenterol. 2010; 105:2389–2395.
crossref
6. Leroith D. Pathophysiology of the metabolic syndrome: implications for the cardiometabolic risks associated with type 2 diabetes. Am J Med Sci. 2012; 343:13–16.
crossref
7. Safar ME, Balkau B, Lange C, et al. Hypertension and vascular dynamics in men and women with metabolic syndrome. J Am Coll Cardiol. 2013; 61:12–19.
crossref
8. Grundy SM. Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol. 2012; 59:635–643.
crossref
9. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010; 51:679–689.
crossref
10. Qiao Q, Nyamdorj R. Is the association of type II diabetes with waist circumference or waist-to-hip ratio stronger than that with body mass index? Eur J Clin Nutr. 2010; 64:30–34.
crossref
11. Sull JW, Yun JE, Lee SY, et al. Body mass index and serum aminotransferase levels in Korean men and women. J Clin Gastroenterol. 2009; 43:869–875.
crossref
12. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005; 172:367–379.
crossref
13. Ruhl CE, Everhart JE. Trunk fat is associated with increased serum levels of alanine aminotransferase in the United States. Gastroenterology. 2010; 138:1346–1356.e3.
crossref
14. Dong MH, Bettencourt R, Brenner DA, Barrett-Connor E, Loomba R. Serum levels of alanine aminotransferase decrease with age in longitudinal analysis. Clin Gastroenterol Hepatol. 2012; 10:285–290.e1.
crossref
15. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003; 98:960–967.
crossref
16. Bambha K, Belt P, Abraham M, et al. Nonalcoholic Steatohepatitis Clinical Research Network Research Group. Ethnicity and nonalcoholic fatty liver disease. Hepatology. 2012; 55:769–780.
crossref
17. Rahmioglu N, Andrew T, Cherkas L, et al. Epidemiology and genetic epidemiology of the liver function test proteins. PLoS One. 2009; 4:e4435.
crossref
18. Wannamethee SG, Shaper AG, Lennon L, Whincup PH. Hepatic enzymes, the metabolic syndrome, and the risk of type 2 diabetes in older men. Diabetes Care. 2005; 28:2913–2918.
crossref
19. Fraser A, Harris R, Sattar N, Ebrahim S, Davey Smith G, Lawlor DA. Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women's Heart and Health Study and meta-analysis. Diabetes Care. 2009; 32:741–750.
20. Goessling W, Massaro JM, Vasan RS, D'Agostino RB Sr, Ellison RC, Fox CS. Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology. 2008; 135:1935–1944.e1.
crossref
21. van Beek JH, de Moor MH, de Geus EJ, et al. The genetic archi-tecture of liver enzyme levels: GGT, ALT and AST. Behav Genet. 2013; 43:329–339.
crossref
22. Schneider AL, Lazo M, Ndumele CE, et al. Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communi-ties (ARIC) Study. Diabet Med. 2013; 30:926–933.
crossref

Fig. 1.
The distribution of range of ALT levels according to age and BMI in male subjects. The range of ALT level varied widely according to the increase in BMI, and this finding was more prominent in younger subjects than in older subjects.
kjg-64-213f1.tif
Fig. 2.
The distribution of range of ALT levels according to age and BMI in female subjects. The range of ALT level varied more widely according to the increase in BMI in males than in females, and this finding was more prominent in younger subjects than in older subjects.
kjg-64-213f2.tif
Fig. 3.
The distribution of range of AST levels according to age and BMI in male subjects. The range of AST level varied widely according to the increase in BMI in male subjects, and this finding was more prominent in younger subjects than in older subjects.
kjg-64-213f3.tif
Fig. 4.
The distribution of range of AST levels according to age and BMI in female subjects.
kjg-64-213f4.tif
Fig. 5.
The distribution of range of GGT levels according to age and BMI in male subjects. The range of GGT level varied widely according to the increase in BMI, and this finding was more prominent in younger subjects than in older subjects.
kjg-64-213f5.tif
Fig. 6.
The distribution of range of GGT levels according to age and BMI in female subjects. The range of GGT level varied more widely according to the increase in BMI in males than in females, and this finding was more prominent in younger subjects than in older subjects.
kjg-64-213f6.tif
Table 1.
Baseline Characteristics of the Study Subjects
Characteristic Total Males Females
Subjects (n) 65,715 34,915 30,800
Age (yr) a 47 (38–55) 47 (39–55) 47 (38–55)
Height (cm) a 164.8 (158.4-171.1) 170.6 (166.6-174.5) 158.2 (154.6-161.9)
Body weight (kg) a 63.0 (54.6-71.9) 70.7 (65.0-76.9) 54.6 (50.4-59.5)
BMI (kg/m2) a 23.3 (21.2-25.4) 24.4 (22.7-26.1) 21.8 (20.0-23.9)
ALT (IU/L) a 20 (14–30) 25 (18–36) 16 (12–21)
AST (IU/L) a 21 (18–26) 23 (19–29) 20 (17–24)
GGT (IU/L) a 22 (15–37) 32 (22–51) 15 (12–20)
Systolic BP (mmHg) a 116 (106–128) 120 (111–130) 111 (102–123)
Diastolic BP (mmHg) a 75 (68–84) 80 (72–87) 70 (64–79)
Fasting glucose (mg/dL) a 95 (88–103) 98 (91–106) 92 (86–99)
Triglyceride (mg/dL) a 94 (67–138) 114 (81–165) 77 (59–107)
HDL-cholesterol (mg/dL) a 53 (44–63) 48 (41–56) 59 (50–68)
Obesity (BMI ≥25 kg/m2) 18,749 (28.5) 13,955 (40.0) 4,794 (15.6)
BP ≥130 / ≥85 mmHg 20,056 (30.5) 13,914 (39.9) 6,142 (19.9)
Fasting glucose ≥100 mg/dL 22,176 (33.7) 15,316 (43.9) 6,860 (22.8)
Triglycerides ≥150 mg/dL 13,781 (21.0) 10,769 (30.8) 3,012 (9.8)
HDL-C <40 mg/dL (male); <50 mg/dL (female) 13,883 (21.1) 6,441 (18.5) 7,442 (24.2)

Values are presented as n only, median (interquartile range), or n (percentile).

BP, blood pressure.

a Data are expressed as median and interquartile range because age, BMI, liver enzyme levels, and risk factors for metabolic syndrome were all skewed and did not fit a standard normal distribution.

Table 2.
Multivariate Linear Regression Coefficients of Age and BMI to Log-Transformed Liver Enzyme Levels in Male Subjects
  Age
BMI
R-squared c
Unstandardized coefficient (SD) a Standardized coefficient (95% CI) b p-value Unstandardized coefficient (SD) a Standardized coefficient (95% CI) b p-value
ALT −0.00211 (0.00022) −0.04812 (−0.05775-−0.03849) <0.0001 0.07277 (0.00090) 0.39591 (0.38629-0.40554) <0.0001 0.1605
AST 0.00279 (0.00014) 0.10044 (0.09035-0.11053) <0.0001 0.03086 (0.00060) 0.26439 (0.25431-0.27448) <0.0001 0.0777
GGT 0.00102 (0.00027) 0.01884 (0.00887-0.02881) 0.0002 0.07133 (0.00115) 0.31547 (0.30550-0.32543) <0.0001 0.0993

a Calculated by multivariate regression analysis using log-transformed liver enzyme levels as a dependent variable, and age and BMI as independent variables.

b Calculated by multivariate regression analysis after standardizing the independent variables to make their variances into 1. Standardized coefficient enables comparison of the effect of independent variables with different units on the dependent variables.

c Introduced for estimation of the percentage of explanatory power of each multivariate regression analysis for each liver enzyme.

Table 3.
Multivariate Linear Regression Coefficients of Age and BMI to Log-Transformed Liver Enzyme Levels in Female Subjects
  Age
BMI
R-squared c
Unstandardized coefficient (SD) a Standardized coefficient (95% CI) b p-value Unstandardized coefficient (SD) a Standardized coefficient (95% CI) b p-value
ALT 0.01045 (0.00023) 0.26233 (0.25115-0.27350) <0.0001 0.03563 (0.00092) 0.22127 (0.21011-0.23244) <0.0001 0.1646
AST 0.00872 (0.00014) 0.35123 (0.33992-0.36254) <0.0001 0.00608 (0.00058) 0.06053 (0.04922-0.07183) <0.0001 0.1440
GGT 0.00860 (0.00024) 0.20698 (0.19544-0.21853) <0.0001 0.03075 (0.00099) 0.18303 (0.17149-0.19458) <0.0001 0.1069

a Calculated by multivariate regression analysis using log-transformed liver enzyme levels as a dependent variable, and age and BMI as independent variables.

b Calculated by multivariate regression analysis after standardizing the independent variables to make their variances into 1. Standardized coefficient enables comparison of the effect of independent variables with different units on the dependent variables.

c Introduced to estimate the percentage of explanatory power of each multivariate regression analysis for each liver enzyme.

Table 4.
The Significant Effect of the Risk Factors for Metabolic Syndrome on the Range of Liver Enzyme Levels in Male Subjects
Liver enzyme Risk factor of metabolic syndrome Median of liver enzyme levels Mann-Whitney U-test a Slope
Risk factor for MS positive vs. negative p-value Unstandardized coefficient (SD) b Standardized coefficient (95% CI) c Variantion inflation factor d p-value R-squared e
ALT Obesity (BMI≥25 kg/m2) 31 vs. 22 −0.0001 0.26245 (0.00548) 0.24616 (0.23608-0.25624) 1.08482 −0.0001 0.1491
  Blood pressure ≥130/≥85 mmHg 27 vs. 24 −0.0001 0.05968 (0.00546) 0.05595 (0.04592-0.06598) 1.07344 −0.0001  
  Fasting glucose ≥100 mg/dL 27 vs. 24 −0.0001 0.06216 (0.00548) 0.05907 (0.04886-0.06927) 1.11206 −0.0001  
  Triglycerides ≥150 mg/dL 31 vs. 23 −0.0001 0.20565 (0.00594) 0.18187 (0.17156-0.19217) 1.13342 −0.0001  
  HDL-cholesterol −40 mg/dL 29 vs. 24 −0.0001 0.07365 (0.00689) 0.05470 (0.04468-0.06473) 1.07173 −0.0001  
AST Obesity (BMI≥25 kg/m2) 25 vs. 22 −0.0001 0.11608 (0.00363) 0.17145 (0.16094-0.18195) 1.08483 −0.0001 0.0761
  Blood pressure ≥130/≥85 mmHg 24 vs. 22 −0.0001 0.04308 (0.00361) 0.06359 (0.05314-0.07404) 1.07344 −0.0001  
  Fasting glucose ≥100 mg/dL 24 vs. 23 −0.0001 0.02511 (0.00363) 0.03757 (0.02694-0.04821) 1.11206 −0.0001  
  Triglycerides ≥150 mg/dL 25 vs. 22 −0.0001 0.09288 (0.00393) 0.12935 (0.11861-0.14008) 1.13344 −0.0001  
  HDL-cholesterol −40 mg/dL 24 vs. 23 −0.0001 −0.01500 (0.00456) −0.01755 (−0.02799-−0.00710) 1.07173 0.001  
GGT Obesity (BMI≥25 kg/m2) 40 vs. 27 −0.0001 0.22062 (0.00661) 0.16821 (0.15833-0.17809) 1.08488 −0.0001 0.1828
  Blood pressure ≥130/≥85 mmHg 37 vs. 29 −0.0001 0.12213 (0.00658) 0.09307 (0.08325-0.10290) 1.07354 −0.0001  
  Fasting glucose ≥100 mg/dL 37 vs. 28 −0.0001 0.16222 (0.00661) 0.12529 (0.11530-0.13529) 1.11178 −0.0001  
  Triglycerides ≥150 mg/dL 45 vs. 28 −0.0001 0.40950 (0.00717) 0.29437 (0.28427-0.30447) 1.13338 −0.0001  
  HDL-cholesterol −40 mg/dL 34 vs. 31 −0.0001 −0.11024 (0.00830) −0.06656 (−0.07638-−0.05673) 1.07178 −0.0001  

MS, metabolic syndrome.

a Mann-Whitney U-test was performed if there were significant differences in the level of liver enzymes according to the existence of each risk factor for metabolic syndrome.

b Calculated by multivariate regression analysis using log-transformed liver enzyme levels as a dependent variable, and age and each risk factor for metabolic syndrome as independent variables.

c Calculated by multivariate regression analysis after standardizing the independent variables to make their variances into 1. Standardized coefficient enables comparison of the effect of independent variables with different units on the dependent variables.

d Variance inflation factor for each risk factor for metabolic syndrome was calculated to quantify the severity of multicollinearity in multivariate regression analysis. There may be no colinearity among the risk factors for metabolic syndrome because variance inflation factor greater than 10 is regarded as suggesting the existence of collinearity.

e R-squared was introduced to estimate the percentage of explanatory power of each multivariate regression analysis for each liver enzyme.

Table 5.
The Significant Effect of the Risk Factors for Metabolic Syndrome on the Range of Liver Enzyme Levels in Female Subjects
Liver enzyme Risk factor of metabolic syndrome Median of liver enzyme levels Mann-Whitney U-test a Slope
Risk factor for MS positive vs. negative p-value Unstandardized coefficient (SD) b Standardized coefficient (95% CI) c Variantion inflation factor d p-value R-squared e
ALT Obesity (BMI ≥25 kg/m2) 20 vs. 15 −0.0001 0.18416 (0.00737) 0.13896 (0.12806-0.14987) 1.13875 −0.0001 0.1640
  Blood pressure ≥130/≥85 mmHg 18 vs. 15 −0.0001 0.02197 (0.00680) 0.01827 (0.00718-0.02936) 1.17735 0.0012  
  Fasting glucose ≥100 mg/dL 19 vs. 15 −0.0001 0.06556 (0.00647) 0.05678 (0.04580-0.06775) 1.15455 −0.0001  
  Triglycerides ≥150 mg/dL HDL-cholesterol −40 mg/dL 21 vs. 15 17 vs. 15 −0.0001 −0.0001 0.15030 (0.00906) 0.02409 (0.00617) 0.09293 (0.08195-0.10390) 0.02146 (0.01068-0.03224) 1.15399 1.11202 −0.0001 −0.0001  
AST Obesity (BMI ≥25 kg/m2) 22 vs. 19 −0.0001 0.05057 (0.00464) 0.06120 (0.05019-0.07221) 1.13879 −0.0001 0.1482
  Blood pressure ≥130/≥85 mmHg 21 vs. 19 −0.0001 0.01047 (0.00428) 0.01397 (0.00277-0.02516) 1.17733 0.0145  
  Fasting glucose ≥100 mg/dL 21 vs. 19 −0.0001 0.00037728 (0.00407) 0.00052397 (–0.01055-0.01160) 1.15442 0.9261  
  Triglycerides ≥150 mg/dL 22 vs. 19 −0.0001 0.05487 (0.00570) 0.05440 (0.04333-0.06548) 1.15387 −0.0001  
  HDL-cholesterol −40 mg/dL 20 vs. 19 −0.0001 −0.02418 (0.00388) −0.03456 (–0.04543-–0.02368) 1.11193 −0.0001  
GGT Obesity (BMI ≥25 kg/m2) 19 vs. 14 −0.0001 0.15822 (0.00782) 0.11440 (0.10331-0.12548) 1.13866 −0.0001 0.1355
  Blood pressure ≥130/≥85 mmHg 17 vs. 14 −0.0001 0.04232 (0.00722) 0.03372 (0.02245-0.04500) 1.17742 −0.0001  
  Fasting glucose ≥100 mg/dL 18 vs. 14 −0.0001 0.12433 (0.00686) 0.10317 (0.09202-0.11433) 1.15418 −0.0001  
  Triglycerides ≥150 mg/dL 21 vs. 15 −0.0001 0.24552 (0.00961) 0.14545 (0.13430-0.15661) 1.15371 −0.0001  
  HDL-cholesterol −40 mg/dL 16 vs. 15 −0.0001 −0.00639 (0.00655) −0.00545 (–0.01641-0.00550) 1.11200 0.3293  

MS, metabolic syndrome.

a Mann-Whitney U-test was performed if there were significant differences in the level of liver enzymes according to the existence of each risk factor for metabolic syndrome.

b Calculated by multivariate regression analysis using log-transformed liver enzyme levels as a dependent variable, and age and each risk factor for metabolic syndrome as independent variables.

c Calculated by multivariate regression analysis after standardizing the independent variables to make their variances into 1. Standardized coefficient enables comparison of the effect of independent variables with different units on the dependent variables.

d Variance inflation factor for each risk factor for metabolic syndrome was calculated to quantify the severity of multicollinearity in multivariate regression analysis. There may be no colinearity among the risk factors for metabolic syndrome because variance inflation factor greater than 10 is regarded as suggesting the existence of collinearity.

e R-squared was introduced to estimate the percentage of explanatory power of each multivariate regression analysis for each liver enzyme.

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