We compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndrome with those
in age and sex-matched subjects without the syndrome. Metabolic syndrome was defi ned by the new
criteria published in Japan, and hepatic enzymes, i.e., aspartate aminotransferase (AST), alanine
aminotransferase (ALT) and &#947;-glutamyl transpeptidase (&#947;GTP), were measured. AST, ALT and
&#947;GTP in subjects with metabolic syndrome were signifi cantly higher than those in subjects without
the syndrome, and metabolic syndrome was closely associated with hepatic enzymes in this cohort of
Japanese men.</p

Makino, Hirofumi

Matsumoto, Sumiko

Miyatake, Nobuyuki

Numata, Takeyuki

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 61, Issue 1 2007 Article 4FEBRUARY 2007Comparison of hepatic enzymes betweenjapanese men with and without metabolicsyndromeNobuyuki Miyatake∗ Sumiko Matsumoto†Hirofumi Makino‡ Takeyuki Numata∗∗∗Okayama Southern Institute of Health,†Okayama Southern Institute of Health,‡Okayama University,∗∗Okayama Southern Institute of Health,Copyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Comparison of hepatic enzymes betweenjapanese men with and without metabolicsyndrome∗Nobuyuki Miyatake, Sumiko Matsumoto, Hirofumi Makino, and TakeyukiNumataAbstractWe compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndromewith those in age and sex-matched subjects without the syndrome. Metabolic syndrome was defined by the new criteria published in Japan, and hepatic enzymes, i.e., aspartate aminotransferase(AST), alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γGTP), were measured.AST, ALT and γGTP in subjects with metabolic syndrome were signifi cantly higher than thosein subjects without the syndrome, and metabolic syndrome was closely aociated with hepaticenzymes in this cohort of Japanese men.KEYWORDS: metabolic syndrome, hepatic enzymes∗PMID: 17332839 [PubMed - in process]Copyright (C) OKAYAMA UNIVERSITY MEDICAL SCHOOLComparison of Hepatic Enzymes between Japanese Men with and without Metabolic SyndromeNobuyuki Miyatakea＊,  Sumiko Matsumotoa,  Hirofumi Makinob,  and Takeyuki NumataaaOkayama Southern Institute of Health,  Okayama 700ﾝ0952,  Japan,  and bDepartment of Medicine and Clinical Science,  Okayama University Graduate School of Medicine,  Dentistry and Pharmaceutical Sciences,  Okayama 700ﾝ8558,  Japanhe metabolic syndrome,  which is characterized by abdominal obesity,  dyslipidemia,  and eleva-tion of blood pressure and fasting plasma glucose lev-els,  is a common disorder in Japan [1,  2].  For example,  in a previous cohort,  30.7ｵ of men and 3.6ｵ of women were diagnosed as having the metabolic syndrome using the new criteria in Japan [1].  The metabolic syndrome has been associated with an increased risk for cardiovascular disease.  However, the link between metabolic syndrome as deﬁ ned using the new criteria in Japan and hepatic enzymes still remains to be investigated.  In the present study, therefore,  we compared the levels of hepatic enzymes in subjects with metabolic syndrome with those in age and sex-matched subjects without the syndrome.Subjects and Methods　　Subjects.　 We used the data of 220 Japanese men with metabolic syndrome and 263 Japanese men without metabolic syndrome,  aged 23ﾝ77 years,  who met all of the following criteria : (1) Received an annual health checkup each year from June 1997 to May 2005 at Okayama Southern Institute of Health ; (2) Received fasting blood examination and a cardiopulmonary exercise test as part of the annual health checkup ; (3) Provided written informed con-sent ; (4) Had no history of hepatitis virus infection, hepatitis B antigen (HBsAg) or antibodies against hepatitis C viruses (Table 1).　　Anthropometric measurements and blood examination. Anthropometric parameters,  i.e., height,  weight,  and waist circumference,  were mea-TWe compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndrome with those in age and sex-matched subjects without the syndrome.  Metabolic syndrome was deﬁ ned by the new criteria published in Japan,  and hepatic enzymes,  i.e.,  aspartate aminotransferase (AST),  alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γGTP),  were measured.  AST,  ALT and γGTP in subjects with metabolic syndrome were signiﬁ cantly higher than those in subjects without the syndrome,  and metabolic syndrome was closely associated with hepatic enzymes in this cohort of Japanese men.Key words : metabolic syndrome,  hepatic enzymesActa Med.  Okayama,  2007Vol.  61,  No.  1,  pp.  31ﾝ34http ://www.lib.okayama-u.ac.jp/www/acta/CopyrightⒸ 2007 by Okayama University Medical School.Short CommunicationReceived May 26, 2006 ; accepted July 28, 2006. ＊Corresponding author. Phone : ＋81ﾝ86ﾝ246ﾝ6250 ; Fax : ＋81ﾝ86ﾝ246ﾝ6330E-mail : center@okakenko.jp (N. Miyatake)1Miyatake et al.: Comparison of hepatic enzymes between japanese men withProduced by The Berkeley Electronic Press, 2007sured.  Body mass index (BMI) was calculated as weight/[height]2 (kg/m2).  The waist circumference was measured at the umbilical level.  Blood examina-tions,  i.e.,  aspartate aminotransferase (AST) by the Wroblewski-Karmen method,  alanine aminotransfer-ase (ALT) by the Wroblewski-Karmen method,  and γ-glutamyl transpeptidase (γGTP) by the L-γ-glutamyl-3-carboxy-4-nitroanilide method,  were also measured.  The institutional normal upper limit of AST was 35 IU/l,  that of ALT was 35 IU/l,  and that of γGTP was 55 IU/l.　　Diagnosis of metabolic syndrome.　 The metabolic syndrome was deﬁ ned,  among men with a waist circumference in excess of 85 cm and women with a waist circumference in excess of 90 cm,  as having 2 or more of following components : 1) Dyslipidemia: triglycerides ≧ 150 mg/dl and/or HDL cholesterol ＜ 40 mg/dl; 2) High blood pressure:blood pressure ≧ 130/85 mmHg; 3) Impaired glucose tolerance: fasting plasma glucose ≧ 110 mg/dl [2].32 Acta Med.  Okayama　Vol.  61,  No.  1Miyatake et al.Table 1　　Comparison of parameters using the criteria and subcriteria of metabolic syndrome in Japanese menMetabolic syndrome (＋) (－) p ValueNumber of Subjects 220 263Age 48.9±10.5 49.3±11.1 0.6937Height (cm) 168.6±5.7 168.3±5.7 0.5336Body weight (kg) 81.4±12.8 71.9±12.1 ＜0.0001Body mass index (kg/m2) 28.6±3.8 25.3±2.5 ＜0.0001AST (IU/L) 29.6±12.9 24.7±9.7 ＜0.0001ALT (IU/L) 43.9±28.3 32.4±22.8 ＜0.0001γGTP (IU/L) 63.6±51.2 46.2±41.9 ＜0.0001Waist Circumference (＋) (－)Number of Subjects 351 132Age 47.6±10.5 53.1±10.7 ＜0.0001AST (IU/L) 28.2±11.8 23.5±10.2 ＜0.0001ALT (IU/L) 42.4±27.7 24.9±15.4 ＜0.0001γGTP (IU/L) 58.3±47.9 43.1±43.5 0.0015Dyslipidemia (＋) (－)Number of Subjects 270 213Age 49.0±10.8 49.2±10.9 0.8311AST (IU/L) 29.0±12.8 24.2±9.0 ＜0.0001ALT (IU/L) 41.9±28.5 32.2±21.5 ＜0.0001γGTP (IU/L) 61.8±52.3 44.4±37.6 ＜0.0001High blood pressure (＋) (－)Number of Subjects 361 122Age 49.7±10.9 47.5±10.6 0.0528AST (IU/L) 27.8±12.2 24.2±9.0 0.0031ALT (IU/L) 38.6±26.6 34.8±24.4 0.1635γGTP (IU/L) 59.2±50.7 39.3±30.1 ＜0.0001Impared glucose tolerance (＋) (－)Number of Subjects 185 298Age 52.5±9.2 47.0±11.2 ＜0.0001AST (IU/L) 26.5±13.6 27.2±10.1 0.5213ALT (IU/L) 37.2±29.6 37.8±23.7 0.7987γGTP (IU/L) 58.4±54.4 51.5±41.8 0.1222Metabolic syndrome (Non drinkers) (＋) (－)Number of Subjects 47 56Age 46.5±12.0 48.2±12.1 0.4765AST (IU/L) 32.2±17.3 23.3±9.7 0.0014ALT (IU/L) 52.7±36.3 32.7±22.2 0.0009γGTP (IU/L) 47.6±30.9 31.7±21.0 0.00262Acta Medica Okayama, Vol. 61 [2007], Iss. 1, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol61/iss1/4　　Alcohol consumption habits.　 The data on alcohol consumption habits were obtained at inter-views by well-trained staﬀ  in a structured way.  The subjects were asked if they currently drank alcohol on a regular basis.  Subjects answering “yes” were classiﬁ ed as current drinkers.  Those answering “no” were further asked whether they had ever drunk alcohol on a regular basis.  Those answering “no” were classiﬁ ed as nondrinker and those answering “yes” were classiﬁ ed as previous drinkers.　　Statistical analysis.　 Data are expressed as the mean ± standard deviation (SD).  The relationship between metabolic syndrome and drinking habits was tested using an χ2 test and parameters were com-pared between groups using an unpaired-t test. Values of p ＜ 0.05 were considered to be statistically signiﬁ cant.Results　　Table 1 and 2 compare the results between sub-jects with and those without metabolic syndrome. There were no signiﬁ cant diﬀ erences in age or drink-ing habits between the 2 groups.  Body weight and BMI in the subjects with metabolic syndrome were signiﬁ cantly higher than those in the controls.  The levels of AST,  ALT and γGTP were also signiﬁ -cantly higher in the subjects with metabolic syn-drome.  We also compared the levels of hepatic enzymes between subjects with and without each com-ponent of the deﬁ nition of metabolic syndrome.  By this analysis,  there was no signiﬁ cant diﬀ erence of age between subjects with or without dyslipidemia or high blood pressure.  However,  there was a signiﬁ -cant diﬀ erence of age between the sub-groups with or without abdominal obesity and impaired glucose tol-erance.  The levels of AST,  ALT and γGTP in sub-jects with abdominal obesity or dyslipidemia were signiﬁ cantly higher than those in subjects without these components of the metabolic syndrome.  AST and γGTP in subjects with elevated blood pressure were also signiﬁ cantly higher than those in subjects with normal blood pressure.　　To strictly avoid the inﬂ uence of alcohol consump-tion habits,  we paerformed a separate analysis using only data of nondrinkers and compared the hepatic enzyme levels between subjects with and those with-out metabolic syndrome.  As in the overall analsysis, the AST,  ALT and γGTP levels in subjects with metabolic syndrome were signiﬁ cantly higher than those in the subjects without the syndrome.Discussion　We compared the hepatic enzyme levels in subjects with metabolic syndrome with those in age and sex-matched controls without metabolic syndrome sub-jects as deﬁ ned using the criteria in Japan.　　Nonalcoholic steatohepatitis represents an advanced stage of fatty liver disease developed in the absence of alcohol abuse and is frequently associated with the metabolic syndrome and type 2 diabetes. The actual prevalence of nonalcoholic steatohepatitis in type 2 diabetes and obesity is unknown.  It is esti-mated that 75ｵ of type 2 diatetic patients present some form of non alcoholic fatty liver of diﬀ erent degrees.  Several genetic and acquired factors are involved in its pathogenesis [3].  Wannamethee et al. reported that elevated levels of ALT and γGTP within the normal range are independent predictors of type 2 diabetes in older men [4].  Nannipieri et al. also reported that mild elevation in hepatic enzymes is associated with features of the metabolic syndrome by follow-up study [5].　　The metabolic syndrome is now considered to reﬂ ect a failure of normal partitioning of surplus fat exclusively into adipose tissue [6,  7].  The failure leads to fat storage in the liver,  muscle and pancre-atic β cells,  which causes hepatic steatosis,  dyslipid-emia,  hepatic and peripheral insulin resistance,  and insulin secretory failure.  Adipocytokines such as leptin and adiponectin are proposed to play a critical role in preventing accumulation of lipids [7].  In this regard,  it is interesting that hypoadiponectinemia has been seen in patients with nonalcoholic steato-33Metabolic Syndrome and Hepatic EnzymesFebruary 2007Table 2　　Relationship between metabolic syndrome and drinking habitsMS (＋) MS (－)Current drinker 168 193Non drinker 47 56Previous drinker 5 14Not signiﬁ cant (p＝0.2258) by χ2 testMS : Metabolic syndrome3Miyatake et al.: Comparison of hepatic enzymes between japanese men withProduced by The Berkeley Electronic Press, 2007hepatitis [8].  In addition,  administration of adipo-nectin has been shown to alleviate nonalcoholic fatty liver disease in mice [9].  In this study,  hepatic enzyme levels in subjects with metabolic syndrome were signiﬁ cantly higher than those in subjects with-out the syndrome,  even after strictly controlling for alcohol consumption.  In addition,  a contribution of waist circumference and dyslipidemia to the develop-ment of liver functional abnormality was noted.　　Potential limitations still remain in our study. First,  the cross-sectional study design in our study makes it diﬃ  cult to infer causality between metabolic syndrome and hepatic enzymes.  Second,  we were not able to evaluate hepatic fat accumulation by using ultrasound systems.  Therefore,  our ﬁ ndings are not fully applicable to clinical and public health practice settings.  In conclusion,  metabolic syndrome was found to be closely linked to hepatic enzymes in a large cohort of Japanese men.  Further intervention studies are necessary to test the eﬀ ect of prevention and treatment of metabolic syndrome on hepatic enzymes.Acknowledgements.　This research was supported in part by Research Grants from the Ministry of Health,  Labor and Welfare, Japan.References 1. Miyatake N,  Kawasaki Y,  Nishikawa H,  Takenami S and Numata T : Prevalence of metabolic syndrome in Okayama prefecture, Japan.  Intern Med (2006) 45 : 107ﾝ108. 2. An examination committee for criterion of metabolic syn-drome : Deﬁ nition and criteria of metabolic syndrome.  Nippon Naika Gakkai Zasshi (2005) 94 : 794ﾝ809 (in Japanese). 3. Brunt EM : Nonalcoholic steatohepatitis.  Semin Liver Dis (2004) 24 : 3ﾝ20. 4. Wannamethee SG,  Shaper AG,  Lennon L and Whincup PH : Hepatic enzymes,  the metabolic syndrome,  and the risk of type 2 diabetes in older men.  Diabetes Care (2005) 28 : 2913ﾝ2918. 5. Nannipieri M,  Gonzales C,  Baldi S,  Posadas R,  Williams K, Haﬀ ner SM,  Stern MP and Ferrannini E : Mexico City diabetes study : Liver enzymes,  the metabolic syndrome,  and incident dia-betes : the Mexico City diabetes study.  Diabetes Care (2005) 28 : 1757ﾝ1762. 6. Lewis GF,  Carpentier A,  Adeli K and Giacca A : Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes.  Endocr Rev (2002) 23 : 201ﾝ229. 7. Unger RH : Minireview : weapons of lean body mass destruc-tion : the role of ectopic lipids in the metabolic syndrome. Endocrinology (2003) 144 : 5159ﾝ5165. 8. Ryo M,  Nakamura T,  Kihara S,  Kumada M,  Shibazaki S, Takahashi M,  Nagai M,  Matsuzawa Y and Funahashi T : Adiponectin as a biomarker of the metabolic syndrome.  Circ J (2004) 68 : 975ﾝ981. 9. Hui JM,  Hodge A,  Farrell GC,  Kench JG,  Kriketos A and George J : Beyond insulin resistance in NASH : TNF-alpha or adiponectin? Hepatology (2004) 40 : 46ﾝ54.34 Acta Med.  Okayama　Vol.  61,  No.  1Miyatake et al.4Acta Medica Okayama, Vol. 61 [2007], Iss. 1, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol61/iss1/4

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