LETTER TO THE EDITOR

Liver enzymes, metabolic syndrome, and insulin resistanceTomoyuki KAWADA

Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan

To the Editor,

Recently, Xu et al.1 confirmed a significant association

between liver enzymes, especially c-glutamyltransferase

(GGT), and metabolic syndrome. Yun et al.2 also

reported that serum alanine aminotransferase (ALT)

was significantly associated with metabolic syndrome

independent of insulin resistance. I think that the main

outcomes of these two studies are correct, but addi-

tional analysis is needed to confirm the conclusions.

There are differences in the association between liver

enzymes and components of metabolic syndrome, pre-

sented in table 7 by Xu et al.1 Although sex differences

exist (tables 3 and 4 presented by Xu et al.1), waist cir-

cumference was not associated with GGT. In contrast,

Yun et al.2 reported that waist circumference was most

strongly associated with ALT, which has also been

reported by Gunji et al.3

In an occupational worksite, the validity of the

homeostasis model assessment of insulin resistance

(HOMA-IR) was reported to decrease for subjects

with fasting plasma glucose levels ‡7.8 mmol ⁄L, with

the percentage of male subjects with fasting plasma

glucose levels ‡7.8 mmol ⁄L approximately 1%.4

Furthermore, a logarithmic transformation of skewed

variables, such as triglyceride, liver enzymes, and

HOMA-IR, is needed.

To determine the effects of insulin resistance on the

association between liver enzymes and metabolic syn-

drome, multiple regression analyses are effective statis-

tical procedures to avoid loss of information. These

procedures were used in an occupational field study

that included evaluation of HOMA-IR, metabolic

components, and some lifestyle factors in 3008 sub-

jects4 (and from which subjects with fasting plasma

glucose levels ‡7.8 mmol ⁄L and subjects who were

positive for HBs antigen or HBc antibody were

excluded). In that study, standard Japanese criteria5

were used to define metabolic components.

In that study, stepwise multiple regression analysis

to predict log-transformed values of serum ALT

according to four components of metabolic syndrome,

log-transformed values of HOMA-IR, and three life-

style factors revealed that the log-transformed values

for HOMA-IR (b = 0.28), waist circumference (b =

0.21), dyslipidemia (b = 0.14), age (b = )0.12), not

smoking (b = 0.06), high blood pressure (b = 0.04),

and regular exercise (b = )0.04) were significantly

associated with serum ALT levels. The adjusted multiple

regression coefficient was 0.261.4

Using the same analysis, log-transformed values for

serum GGT according to four components of metabolic

syndrome, log-transformed values of HOMA-IR, and

three lifestyle factors were predicted. Significant factors

were no alcohol consumption (b = )0.28), dyslipidemia

(b = 0.18), log-transformed values of HOMA-IR

(b = 0.15), waist circumference (b = 0.14), high blood

pressure (b = 0.09), glucose intolerance (b = 0.04),

and regular exercise (b = )0.04). The adjusted multiple

regression coefficient was 0.223.4

Insulin resistance was the strongest predictor of

increases in serum ALT, followed by waist circumfer-

ence and dyslipidemia. In contrast, alcohol consump-

tion was a strong predictor of increases in GGT,

followed by dyslipidemia and insulin resistance.4 I spec-

ulate that increases in liver enzymes can be explained

by liver-overload agents, and that insulin resistance is a

key factor in the elevation of liver enzymes.

Acknowledgment

The author expresses his appreciation to the subjects

who participated in the occupational field study.

Disclosure

None to declare.

Correspondence

Tomoyuki Kawada, Department of Hygiene and Public Health, Nippon

Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602, Japan.

Tel: +81 3 3822 2131; Fax: +81 3 5685 3065

Email: kawada@nms.ac.jp

doi: 10.1111/j.1753-0407.2011.00134.x Journal of Diabetes 3 (2011) 182–183

182 ª 2011 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd

AS

IAT

RA

CK

References

1. Xu Y, Bi YF, Xu M et al. Cross-sectional and longitu-

dinal association of serum alanine aminotransaminase

and c-glutamyltransferase with metabolic syndrome in

middle-aged and elderly Chinese people. J Diabetes.

2011; 3: 38–47.

2. Yun JE, Kim SY, Kang HC, Lee SJ, Kimm H, Jee SH.

Alanine aminotransferase is associated with metabolic

syndrome independently of insulin resistance. Circ J.

2011; 75: 964–9.

3. Gunji T, Matsuhashi N, Sato H et al. Risk factors for

serum alanine aminotransferase elevation: A cross-

sectional study of healthy adult males in Tokyo, Japan.

Dig Liver Dis. 2010; 42: 882–7.

4. Kawada T. Preliminary report: Homeostasis model

assessment of insulin resistance, an indicator of insulin

resistance, is strongly related to serum insulin. Practical

data presentation and the mathematical basis. Metabo-

lism. 2010; 59: 1044–6.

5. Matsuzawa Y.Metabolic syndrome: Definition and diagno-

stic criteria in Japan. J Atheroscler Thromb. 2005; 12: 301.

Letter to the Editor

ª 2011 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd 183

AS

IAT

RA

CK