Alanine Aminotransferase as a Predictor of Metabolic Syndrome in Koreans

Ji Hae Kwon; Yong Seong An; Yang Ho Kang; Seok Man Son; In Ju Kim; Yong Ki Kim

doi:10.3803/jkes.2008.23.6.404

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Kwon, An, Kang, Son, Kim, and Kim: Alanine Aminotransferase as a Predictor of Metabolic Syndrome in Koreans

Original Article

J Korean Endocr Soc 2008;23(6):404-412.

Published online: 10 January 2008

DOI: https://doi.org/10.3803/jkes.2008.23.6.404

Alanine Aminotransferase as a Predictor of Metabolic Syndrome in Koreans

Ji Hae Kwon, Yong Seong An¹, Yang Ho Kang², Seok Man Son², In Ju Kim², Yong Ki Kim²

Department of Internal Medicine, Ulsan Dongkang Hospital, Pusan National University College of Medicine

¹Department of Internal Medicine, Busan Veterans Hospital, Pusan National University College of Medicine

²Deparment of Internal Medicine, Pusan National University College of Medicine

Received 11 August 2008 Accepted 27 October 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims

Alanine aminotransferase (ALT) is associated with insulin resistance, and is independent of the general metabolic measures. Gamma-glutamyltransferase (GGT) is regarded as a predictor of diabetes mellitus. We analyzed which of ALT or GGT is better tool to preestimate the development of metabolic syndrome.

Method

A total of 1203 Koreans who visited the Institute of Health in Pusan National University Hospital from January 2005 to August 2006 were enrolled in this cross-sectional study. Their median age was 51 years old, and the prevalence of metabolic syndrome was 16.4% (n = 197). We excluded the subjects with diabetes mellitus, hypertension and viral hepatitis or those subjects with a level of alanine aminotransferase (ALT) or gamma-glutamyltransferase (r-GGT) > 80 IU/L.

Results

For all the patients in the metabolic syndrome group, the median homeostatic assessment of insulin resistance (HOMA-IR), the waist circumference, the fasting blood glucose level, the systolic and diastolic blood pressure were all associated with the ALT level (P < 0.05). For the nonmetabolic syndrome group, all the metabolic risk factors were associated with the ALT level (P < 0.05). On logistic regression analysis, after correction for age, alcohol intake, HOMA-IR and body mass index, the logALT maintained a highly predictive value for metabolic syndrome, and this was better than the logGGT [odds ratio (OR) of logALT: 18.489, odds ratio of logGGT: 2.024] (P < 0.001). The risk of developing metabolic syndrome was significantly higher in the above 50 percentile and the above 75 percentile of ALT than in the lowest quartile. [for men – OR: 3.6; 95% confidence interval (CI), 2.2–5.9; OR: 6.9; 95% CI: 4.3–10.9] [for women – OR: 2.7; 95% CI: 1.5–4.7; OR: 6.5; 95% CI: 3.8–11] (P < 0.001). The cut-off value of ALT by the ROC curve was 24 IU/L for men (sensitivity: 64.3%, specificity: 66%, negative predictive value: 99.5%) and 20 IU/L for women (sensitivity: 78.9%, specificity: 61.4%, negative predictive value: 84.9%).

Conclusions

Even although patients can have an ALT level that's included within the upper normal level, we may consider the probability that these patients will have metabolic syndrome. Furthermore, in our analysis, the ALT level is a better predictor of metabolic syndrome than the GGT level.

Keywords: alanine aminotransferase, gamma-glutamyltransferase, metabolic syndrome

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Fig. 1–1.

Cut-off value of ALT according to sex (A: men, B: women) to preestimate the incidence of metabolic syndrome. A. MEN The cut-off value of ALT about metabolic syndrome is above 24 IU/L. The sensitivity is 64.29% (95% confidence interval 55.3∼72.6%) and the specificity is 66% (61.7∼70.1%). The negative predictive value is 99.5% and AUC (area under the ROC curve) is 0.701 (95% confidence interval 0.664∼0.737) (P = 0.0001). B. WOMEN The cut-off value of ALT about metabolic syndrome is above 20 IU/L. The sensitivity is 78.87% (95% confidence interval 67.6∼87.7%) and the specificity is 61.43% (57∼65.7%). The negative predictive value is 84.9% and AUC is 0.747 (0.709∼0.782) (P = 0.0001).

Fig. 1–2.

Cut-off value of GGT according to sex (A: men, B: women) to preestimate the incidence of metabolic syndrome. A. MEN The cut-off value of GGT about metabolic syndrome is above 36 IU/L. The sensitivity is 58.82% (95% confidence interval 33∼81.5%) and the specificity is 83.3% (80.1∼86.2%). The negative predictive value is 98.6% and AUC (area under the ROC curve) is 0.71 (95% confidence interval 0.673∼0.745) (P = 0.0033). B. WOMEN The cut-off value of GGT about metabolic syndrome is above 26 IU/L. The sensitivity is 61.11% (95% confidence interval 53.6∼68.3%) and the specificity is 63.71% (58.7∼68.5%). The negative predictive value is 78.2% and AUC is 0.655 (0.614∼0.694) (P = 0.0001).

Table 1–1.

Characteristics of subjects according to the presence of metabolic syndrome

	Total	Metabolic syndrome	Nonmetabolic syndrome
	(n = 1203)	(n = 197)	(n = 1,006)
Age (years)	51.28 ±9.3	54.9 ±8.9	50.6 ±9.2
Smoking (1 or 2)	N = 438	N = 86	N = 352
	(36.4% of total)	(43.65% among smoker)*	(56.35%)
Alcohol (1 or 2)	N = 555	N = 114	N = 441 (42.13%)
	(46.13% of total)	(57.87% among alcohol drinker)
SBP (mmHg)	123.77 ±18.58	142.08 ±14.39*	120.19 ±17.15
DBP (mmHg)	76.41 ±11.66	86.82 ± 9.03^†	74.37 ±11.02
ALT (IU/L)	23.63 ±11.61	32.47 ±15.49*	21.9 ±9.81
AST (IU/L)	24.21 ±7.14	27.37 ±8.63*	23.59 ±6.64
GGT (IU/L)	30.92 ±31.84	44.69 ±36.3*	28.23 ±30.2
HOMA-IR	1.24 ±0.97	1.83 ±1.31*	1.13 ±0.84
BMI (kg/m²)	24.14 ±2.84	25.5 ±2.9	23.88 ±2.75
Waist (cm)	83.05 ±8.76	90.33 ±6.84*	81.62 ±8.38
TG (mg/dL)	124.26 ±90.41	188.46 ±105.58*	111.7 ±81.5
HDL-C (mg/dL)	54.7 ±13.1	46.2 ±10.78*	56.37 ±12.87
FBS (mg/dL)	92.61 ±19.57	106.62 ±26.98*	89.9 ±16.4

Data are means ±SD. Smoking (0: no smoking history, 1: previous smoking, 2: current smoking); Alcohol (0: no alcohol, 1: 1∼2 times/week, 2: ≥ 3 times/week); ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; DBP, diastolic blood pressure; FBS, fasting blood sugar; GGT, r-glutamyltransferase; HDL-C, high density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment–insulin resistance; PP, pulse pressure; SBP, systolic blood pressure; TG, triglyceride.

^* P < 0.001, †P < 0.05, metabolic syndrome vs nonmetabolic syndrome.

Table 1–2.

Mean difference of metabolic risk factors according to sex

Metabolic syndrome (Yes or No)	MEN		WOMEN
Metabolic syndrome (Yes or No)	Y	N	Y	N
Age (years)	53.7 ±8.8	50.6 ±9.4	56.9 ±8.9	50.5 ±9.1
Smoking (1 or 2)	N = 81	N = 330	N = 5^†	N = 22^†
Alcohol (1 or 2)	N = 101	N = 355	N = 13	N = 86
SBP (mmHg)	141.2 ±15.4	122.4 ±16.2	43.7 ±12.3*	118 ±17.8
DBP (mmHg)	87.6 ±9.6	76.3 ±10.8	85.4 ±7.8^†	72.4 ±10.8
ALT (IU/L)	33.3 ±15.9*	23.1 ±9.6	31 ±14.7*	20.7 ±9.8
AST (IU/L)	27 ±8.2^†	24.1 ±6.5	28 ± 9.4^†	23 ±6.8
GGT (IU/L)	49 ±38.5*	30.6 ±30.1	37.1 ±31^†	25.9 ±30.1
HOMA-IR	1.9 ±1.35*	1.2 ±0.9	1.7 ±1.2*	1.1 ±1.2
BMI (kg/m²)	25.3 ±2.5	24 ±2.7	25.8 ±3.6*	23.7 ±2.8
Waist (cm)	90.1 ±6.1*	82.4 ±8.3	90.8 ±8	81 ±8.4
TG (mg/dL)	202.4 ±117.2*	122.9 ±71	163.7 ±75.6	100.5 ±89.4
HDL-C (mg/dL)	45.8 ±9.9*	56.5 ±12.7	46.9 ±12.1	56.3 ±13
FBS (mg/dL)	108.7 ±28.9*	91.6 ±17.4	102.9 ±22.9*	88.2 ±15.3

^* P < 0.001

^† P < 0.05.

Table 2.

Pearson's correlations between hepatic enzymes and metabolic risk factor in the presence and absence of metabolic syndrome (Men + Women)

Metabolic syndrome (Yes or No)	Hepatic enzymes	Alcohol	HOMA-IR	BMI	Waist	TG	HDL	FBS	SBP	DBP
Y	ALT	0.094	0.468*	0.136	0.23^†	0.018	–0.009	0.644*	–0.175^†	–0.141^†
	AST	0.048	0.33*	0.149^†	0.133	0.116	–0.075	0.413*	–0.007	–0.01
	GGT	0.21^†	0.206^†	0.057	0.125	0.076	0.08	0.419*	–0.015	0.05
N	ALT	0.097^†	0.38*	0.146*	0.276*	0.112*	–0.112*	0.705*	0.097^†	0.084^†
	AST	0.062	0.24*	0.078^†	0.089^†	0.086^†	0.1^†	0.409*	0.117*	0.102^†
	GGT	0.075^†	0.216*	0.081^†	0.182*	0.01	–0.054	0.308*	0.083^†	0.067^†

^* P < 0.001

^† P < 0.05.

Table 3.

Logistic regression between study variables and metabolic syndrome

Variables	Odds ratio	P
LogALT	18.489	< 0.001
LogALT	–0.49	0.466
LogALT	2.024	0.022

This results are adjusted for age, HOMA-IR, BMI and alcohol.

Table 4–1.

Risk for metabolic syndrome according to ALT levels

	ALT level below 25 percentiles	ALT level within 25∼50 percentiles	ALT level within 50∼75 percentiles	ALT level above 75 percentiles
Men (IU/L)	6∼17	18∼22	23∼30	31∼77
Odds Ratio (95% confidence interval)	1	1.7 (1∼2.8)	3.6 (2.2∼5.9)*	6.9 (4.3∼10.9)*
Women (IU/L)	6∼15	16∼19	20∼25	26∼77
Odds Ratio (95% confidence interval)	1	1.2 (0.6∼2.3)	2.7 (1.5∼4.7)*	6.5 (3.8∼11)*

^* P < 0.001.

Table 4–2.

Risk for metabolic syndrome according to GGT levels

	GGT level below 25 percentiles	GGT level within 25∼50 percentiles	GGT level within 50∼75 percentiles	GGT level above 75 percentiles
Men (IU/L)	5∼15	16∼23	24∼41	42∼389
Odds Ratio (95% confidence interval)	1	1.7 (1∼2.9)	3.2 (2∼5.2)*	5.9 (3.7∼9.4)*
Women (IU/L)	5∼13	14∼18	19∼30	31∼389
Odds Ratio (95% confidence interval)	1	2.4 (1.3∼4.6)	3.1 (1.7∼5.6)*	7.2 (4.1∼12.5)*

^* P < 0.001.

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