Serum γ-Glutamyltransferase and Risk of Metabolic Syndrome and Type 2 Diabetes in Middle-Aged Japanese Men

Noriyuki Nakanishi; Kenji Suzuki; Kozo Tatara

doi:10.2337/diacare.27.6.1427

Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes

Serum γ-Glutamyltransferase and Risk of Metabolic Syndrome and Type 2 Diabetes in Middle-Aged Japanese Men

Noriyuki Nakanishi, MD, DRPH1,
Kenji Suzuki, SCD2 and
Kozo Tatara, MD1

¹Department of Social and Environmental Medicine F2, Course of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
²Japan Labor and Welfare Association, Tokyo, Japan

Address correspondence and reprint requests to Noriyuki Nakanishi, Department of Social and Environmental Medicine, Course of Social Medicine, Osaka University Graduate School of Medicine F2, 2-2 Yamada-oka, Suita-shi, Osaka 565-0871, Japan. E-mail: noriyuki{at}pbhel.med.osaka-u.ac.jp

Diabetes Care 2004 Jun; 27(6): 1427-1432. https://doi.org/10.2337/diacare.27.6.1427

Article Figures & Tables

Tables

Table 1—

Characteristics of 3,599 Japanese male office workers in relation to serum GGT levels

Characteristics	GGT (units/l)						P for trend*
Characteristics		<15	15–21	22–31	32–52	≥53	P for trend*
n	663	775	712	695	754
Age (years)	46.5 ± 6.7	47.3 ± 6.4	47.0 ± 6.3	47.6 ± 6.1	47.9 ± 5.7	<0.001
Family history of diabetes	7.7	9.4	9.8	7.5	10.3	0.325
BMI (kg/m²)	22.2 ± 2.2	23.1 ± 2.4	23.7 ± 2.6	24.2 ± 2.7	24.3 ± 2.8	<0.001
Current drinkers	71.0	81.9	86.7	91.2	93.9	<0.001
Current smokers	43.7	46.3	51.5	53.4	56.4	<0.001
Regular physical activity at least once a week	51.3	52.1	52.1	57.0	53.3	0.143
Systolic blood pressure (mmHg)	122.8 ± 14.8	126.2 ± 14.3	127.7 ± 14.2	130.5 ± 15.1	133.8 ± 15.4	<0.001
Diastolic blood pressure (mmHg)	73.9 ± 10.6	76.5 ± 10.6	78.3 ± 10.4	80.2 ± 11.1	82.4 ± 11.1	<0.001
Total cholesterol (mmol/l)	4.68 ± 0.70	4.95 ± 0.73	5.04 ± 0.81	5.13 ± 0.82	5.28 ± 0.91	<0.001
HDL cholesterol (mmol/l)	1.42 ± 0.30	1.39 ± 0.32	1.37 ± 0.36	1.38 ± 0.36	1.41 ± 0.34	0.035
Triglycerides (mmol/l)	0.86 (0.64–0.19)	1.04 (0.78–1.47)	1.20 (0.85–1.74)	1.35 (1.00–2.04)	1.70 (1.14–2.54)	<0.001
Fasting plasma glucose (mmol/l)	5.03 ± 0.77	5.13 ± 0.65	5.20 ± 0.92	5.27 ± 0.94	5.38 ± 1.05	<0.001
WBC count (10⁹ cells/l)	6.12 ± 1.71	6.36 ± 1.58	6.59 ± 1.69	6.68 ± 1.77	6.82 ± 1.67	<0.001
AST (units/l)	17 (15–20)	19 (17–22)	20 (17–24)	22 (20–27)	27 (23–35)	<0.001
ALT (units/l)	14 (11–17)	17 (14–23)	21 (16–28)	24 (18–33)	31 (24–42)	<0.001
Alkaline phosphatase (units/l)	161 (142–183)	161 (143–186)	164 (146–186)	164 (144–188)	172 (151–197)	<0.001
Metabolic syndrome	4.4	9.0	14.6	23.2	28.0	<0.001
Type 2 diabetes	3.2	5.8	7.0	9.5	11.3	<0.001

Data are means ± SD, percent, or median (interquartile range).
*
↵* Quadratic trend for HDL cholesterol.

Table 2—

The risk of incidence of the metabolic syndrome among 2,957 metabolic syndrome-free Japanese men during 7 years of follow-up in relation to serum liver enzyme levels

Outcome	Liver enzyme						P for trend
Outcome		Quintile 1	Quintile 2	Quintile 3	Quintile 4	Quintile 5	P for trend
GGT (units/l)	<14 (n = 526)	14–19 (n = 602)	20–28 (n = 638)	29–48 (n = 594)	≥49 (n = 597)
Cases/person-years	42/3,235	96/3,557	118/3,669	161/3,213	191/3,085
Incidence density (per 1,000 person-years)	13.0	27.0	32.2	50.1	61.9
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	2.05 (1.43–2.95)	2.44 (1.72–3.47)	3.74 (2.66–5.25)	4.56 (3.26–6.37)	<0.001
Model 2†	1.0 (referent)	1.49 (1.03–2.15)	1.55 (1.08–2.22)	2.28 (1.61–3.25)	2.92 (2.05–4.17)	<0.001
Model 3‡	1.0 (referent)	1.37 (0.95–1.98)	1.35 (0.93–1.95)	1.91 (1.31–2.77)	2.23 (1.51–3.30)	<0.001
ALT (units/l)	<14 (n = 560)	14–16 (n = 457)	17–21 (n = 692)	22–28 (n = 631)	≥29 (n = 617)
Cases/person-years	59/3,384	54/2,704	116/4,014	160/3,491	219/3,165
Incidence density (per 1,000 person-years)	17.4	20.0	28.9	45.8	69.2
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	1.13 (0.78–1.63)	1.63 (1.19–2.23)	2.58 (1.91–3.47)	3.87 (2.90–5.16)	<0.001
Model 2†	1.0 (referent)	0.99 (0.68–1.43)	1.25 (0.91–1.71)	1.64 (1.21–2.22)	2.06 (1.54–2.77)	<0.001
Model 3‡	1.0 (referent)	0.89 (0.61–1.30)	1.07 (0.76–1.49)	1.27 (0.89–1.80)	1.42 (0.95–2.11)	0.093
AST (units/l)	<17 (n = 511)	17–18 (n = 455)	19–21 (n = 743)	22–25 (n = 624)	≥26 (n = 624)
Cases/person-years	68/3,070	74/2,664	129/4,332	159/3,370	178/3,322
Incidence density (per 1,000 person-years)	22.1	27.8	29.8	47.2	53.6
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	1.24 (0.90–1.73)	1.33 (0.99–1.79)	2.07 (1.56–2.75)	2.34 (1.77–3.10)	<0.001
Model 2†	1.0 (referent)	1.18 (0.84–1.63)	1.12 (0.83–1.50)	1.70 (1.27–2.27)	1.75 (1.32–2.32)	<0.001
Model 3‡	1.0 (referent)	1.00 (0.71–1.40)	0.85 (0.62–1.17)	1.04 (0.73–1.48)	0.92 (0.63–1.34)	0.774
Alkaline phosphatase (units/l)	<140 (n = 583)	140–155 (n = 586)	156–170 (n = 590)	171–191 (n = 578)	≥192 (n = 620)
Cases/person-years	84/3,433	121/3,334	122/3,348	131/3,225	150/3,419
Incidence density (per 1,000 person-years)	24.5	36.3	36.4	40.6	43.9
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	1.47 (1.11–1.94)	1.48 (1.12–1.96)	1.64 (1.25–2.16)	1.76 (1.35–2.30)	<0.001
Model 2†	1.0 (referent)	1.40 (1.06–1.86)	1.44 (1.09–1.90)	1.82 (1.38–2.40)	1.66 (1.27–2.18)	<0.001
Model 3‡	1.0 (referent)	1.39 (1.05–1.84)	1.41 (1.06–1.86)	1.73 (1.31–2.28)	1.49 (1.13–1.95)	0.003

*
↵* Model 1: adjustment for age;
†
↵† model 2: model 1 plus adjustment for family history of diabetes, BMI, alcohol intake, cigarette smoking, regular physical activity, and WBC count;
‡
↵‡ model 3: model 2 plus adjustment for all of the other liver enzymes.

Table 3—

The risk of incidence of type 2 diabetes among 3,260 nondiabetic Japanese men during 7 years of follow-up in relation to serum liver enzyme levels

Outcome	Liver enzyme						P for trend
Outcome		Quintile 1	Quintile 2	Quintile 3	Quintile 4	Quintile 5	P for trend
GGT (units/l)	<15 (n = 625)	15–20 (n = 595)	21–30 (n = 709)	31–52 (n = 679)	≥53 (n = 652)
Cases/person-years	18/3,984	40/3,713	58/4,353	77/4,091	83/3,909
Incidence density (per 1,000 person-years)	4.5	10.8	13.3	18.8	21.2
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	2.31 (1.33–4.03)	2.89 (1.70–4.90)	4.01 (2.40–6.70)	4.42 (2.65–7.36)	<0.001
Model 2†	1.0 (referent)	1.79 (1.02–3.13)	2.04 (1.19–3.51)	2.68 (1.57–4.57)	3.06 (1.77–5.30)	<0.001
Model 3‡	1.0 (referent)	1.55 (0.88–2.72)	1.77 (1.01–3.08)	2.08 (1.18–3.66)	2.44 (1.34–4.46)	<0.001
ALT (units/l)	<14 (n = 568)	14–17 (n = 717)	18–22 (n = 575)	23–30 (n = 700)	≥31 (n = 700)
Cases/person-years	23/3,577	40/4,451	48/3,566	59/4,319	106/4,138
Incidence density (per 1,000 person-years)	6.4	9.0	13.5	13.7	25.6
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	1.36 (0.81–2.27)	2.07 (1.26–3.40)	2.15 (1.33–3.49)	4.07 (2.59–6.39)	<0.001
Model 2†	1.0 (referent)	1.30 (0.78–2.17)	1.71 (1.04–2.81)	1.71 (1.05–2.81)	2.47 (1.54–3.95)	<0.001
Model 3‡	1.0 (referent)	1.23 (0.72–2.07)	1.55 (0.90–2.67)	1.52 (0.85–2.72)	2.07 (1.07–3.98)	0.030
AST (units/l)	<17 (n = 512)	17–19 (n = 749)	20–21 (n = 519)	22–26 (n = 813)	≥27 (n = 667)
Cases/person-years	29/3,227	42/4,705	40/3,276	84/4,879	81/3,964
Incidence density (per 1,000 person-years)	9.0	8.9	12.2	17.2	20.4
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	0.97 (0.67–1.56)	1.33 (0.83–2.15)	1.84 (1.20–2.80)	2.20 (1.44–3.37)	<0.001
Model 2†	1.0 (referent)	0.90 (0.56–1.44)	1.28 (0.79–2.07)	1.50 (0.98–2.31)	1.54 (1.00–2.38)	0.002
Model 3‡	1.0 (referent)	0.73 (0.45–1.19)	0.92 (0.55–1.55)	0.89 (0.52–1.51)	0.75 (0.41–1.36)	0.659
Alkaline phosphatase (units/l)	<140 (n = 632)		≥193 (n = 670)
Cases/person-years	38/3,954	50/3,992	52/4,155	56/3,919	80/4,031
Incidence density (per 1,000 person-years)	9.6	12.5	12.5	14.3	19.8
Adjusted relative risk (95% CI)
Model 1*	1.0 (referent)	1.30 (0.85–1.99)	1.32 (0.87–2.01)	1.49 (0.99–2.25)	2.04 (1.39–3.00)	<0.001
Model 2†	1.0 (referent)	1.28 (0.84–1.96)	1.33 (0.88–2.03)	1.38 (0.91–2.10)	1.73 (1.16–2.59)	0.008
Model 3‡	1.0 (referent)	1.24 (0.81–1.90)	1.23 (0.81–1.88)	1.25 (0.82–1.90)	1.48 (0.99–2.23)	0.084

*
↵* Model 1: adjustment for age;
†
↵† model 2: model 1 plus adjustment for family history of diabetes, BMI, alcohol intake, cigarette smoking, regular physical activity, fasting plasma glucose level, and WBC count;
‡
↵‡ model 3: model 2 plus adjustment for all of the other liver enzymes.