Serum Gamma-Glutamyltransferase, Daily Alcohol Consumption, and the Risk of Chronic Kidney Disease: The Kansai Healthcare Study.

BACKGROUND: Serum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR). METHODS: We prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ≥1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m2. RESULTS: During the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (≥71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (≤25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (≥58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR. CONCLUSION: In middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease.

BACKGROUND: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. METHODS: A prospective cohort study of 9,116 middle-aged nondiabetic -Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1-23.0 g ethanol/day), moderate drinkers (23.1-46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. RESULTS: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11-1.70), 1.58 (95% CI 1.28-1.95), 2.27 (95% CI 1.86-2.77), and 3.12 (95% CI 2.56-3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46-0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. CONCLUSIONS: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.

The Association Between Metabolically Healthy Obesity and the Risk of Proteinuria: The Kansai Healthcare Study.

BACKGROUND: Metabolically healthy obesity seems to be a unique phenotype for the risk of cardiometabolic diseases. However, it is not known whether this phenotype is associated with the risk of proteinuria. METHODS: Study subjects were 9,185 non-diabetic Japanese male workers aged 40-55 years who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive or lipid-lowering medications at baseline. Obesity was defined as body mass index ≥25.0 kg/m2. Metabolic health was defined as the presence of no Adult Treatment Panel III components of the metabolic syndrome criteria, excluding waist circumference, and metabolic unhealth was defined as the presence of one or more metabolic syndrome components, excluding waist circumference. "Consecutive proteinuria" was considered positive if proteinuria was detected twice consecutively as 1+ or higher on urine dipstick at annual examinations to exclude chance proteinuria as much as possible. RESULTS: During the 81,660 person-years follow-up period, we confirmed 390 cases of consecutive proteinuria. Compared with metabolically healthy non-obesity, metabolically healthy obesity was not associated with the risk of consecutive proteinuria (multiple-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.37-1.99), but metabolically unhealthy non-obesity with ≥2 metabolic syndrome components (HR 1.77; 95% CI, 1.30-2.42), metabolically unhealthy obesity with one component (HR 1.71; 95% CI, 1.12-2.61), and metabolically unhealthy obesity with ≥2 metabolic syndrome components (HR 2.77; 95% CI, 2.01-3.82) were associated with an increased risk of consecutive proteinuria. CONCLUSIONS: Metabolically healthy obesity did not increase the risk of consecutive proteinuria in Japanese middle-aged men.

Blood pressure components and the risk for proteinuria in Japanese men: The Kansai Healthcare Study.

BACKGROUND: We examined prospectively which of the four blood pressure (BP) components (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean arterial pressure [MAP]) was best in predicting the risk of proteinuria. METHODS: This prospective study included 9341 non-diabetic Japanese middle-aged men who had no proteinuria and an estimated glomerular filtration rate ≥60 mL/min/1.73 m2 and were not taking antihypertensive medications at entry. Persistent proteinuria was defined if proteinuria was detected two or more times consecutively and persistently at the annual examination until the end of follow-up. We calculated the difference in values of Akaike's information criterion (ΔAIC) in comparison of the BP components-added model to the model without them in a Cox proportional hazards model. RESULTS: During the 84,587 person-years follow-up period, we confirmed 151 cases of persistent proteinuria. In multiple-adjusted models that included a single BP component, the hazard ratios for persistent proteinuria for the highest quartile of SBP, PP, and MAP were 3.11 (95% confidence interval [CI], 1.79-5.39), 1.87 (95% CI, 1.18-2.94), and 2.21 (95% CI, 1.33-3.69) compared with the lowest quartile of SBP, PP, and MAP, respectively. The hazard ratio for the highest quartile of DBP was 2.69 (95% CI, 1.65-4.38) compared with the second quartile of DBP. Of all models that included a single BP component, those that included SBP alone or DBP alone had the highest values of ΔAIC (14.0 and 13.1, respectively) in predicting the risk of persistent proteinuria. CONCLUSIONS: Of all BP components, SBP and DBP were best in predicting the risk of persistent proteinuria in middle-aged Japanese men.

Relationship Between Alcohol Drinking Pattern and Risk of Proteinuria: The Kansai Healthcare Study.

BACKGROUND: Moderate alcohol consumption has been reported to be associated with a decreased risk of cardiometabolic diseases. Whether drinking pattern is associated with the risk of proteinuria is unknown. METHODS: Study subjects were 9154 non-diabetic Japanese men aged 40-55 years, with an estimated glomerular filtration rate ≥60 mL/min/1.73 m(2), no proteinuria, and no use of antihypertensive medications at entry. Data on alcohol consumption were obtained by questionnaire. We defined "consecutive proteinuria" as proteinuria detected twice consecutively as 1+ or higher on urine dipstick at annual examinations. RESULTS: During the 81 147 person-years follow-up period, 385 subjects developed consecutive proteinuria. For subjects who reported drinking 4-7 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was significantly associated with a decreased risk of consecutive proteinuria (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.36-0.80) compared with non-drinkers. However, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with an increased risk of consecutive proteinuria (HR 1.78; 95% CI, 1.01-3.14). For subjects who reported drinking 1-3 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was associated with a decreased risk of consecutive proteinuria (HR 0.76; 95% CI, 0.51-1.12), and alcohol consumption of ≥69.1 g ethanol/drinking day was associated with an increased risk of consecutive proteinuria (HR 1.58; 95% CI, 0.72-3.46), but these associations did not reach statistical significance. CONCLUSIONS: Men with frequent alcohol consumption of 0.1-23.0 g ethanol/drinking day had the lowest risk of consecutive proteinuria, while those with frequent alcohol consumption of ≥69.1 g ethanol/drinking day had an increased risk of consecutive proteinuria.

Drinking pattern and risk of chronic kidney disease: the kansai healthcare study.

BACKGROUND/AIMS: The association between alcohol consumption and the risk of chronic kidney disease (CKD) has been reported. What is not known is whether drinking pattern combined with the weekly frequency of alcohol consumption and the quantity per drinking day is associated with the risk of CKD. METHODS: We enrolled 9,112 Japanese nondiabetic men aged 40 to 55 years with absence of proteinuria, an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m(2) or higher, and not on antihypertensive medications at baseline. CKD was defined if eGFR was <60 ml/min/1.73 m(2). The weekly frequency classification was nondrinkers, 1-3 drinking days/week, or 4-7 drinking days/week. The quantity consumed per drinking day was classified as 0.1-23.0 g ethanol/drinking day, 23.1-46.0 g ethanol/drinking day, 46.1-69.0 g ethanol/drinking day, and ≥69.1 g ethanol/drinking day. RESULTS: During the 79,099 person-years, 1,253 subjects developed CKD. Compared to nondrinkers, those who consumed 23.1-46.0 or 46.1-69.0 g ethanol/drinking day on 4-7 drinking days/week had a decreased risk of CKD (multiple-adjusted hazard ratio (HR) 0.62 (0.52-0.74) and 0.76 (0.59-0.97), respectively). The association between the quantity per drinking day and the incidence of CKD was U-shaped among each category of the weekly frequency. HRs within similar categories of quantity per drinking day were lower in the 4-7 drinking days/week group than in the 1-3 drinking days/week group. CONCLUSION: Among middle-aged Japanese men, the people who drank middle-range quantity, specifically who drank 4-7 days/week, had lower risk of CKD than nondrinkers.

Sleep duration and the risk of future lipid profile abnormalities in middle-aged men: the Kansai Healthcare Study.

BACKGROUND: Although short sleep duration has been reported to be associated with future cardiometabolic diseases, it is not fully understood whether sleep duration is prospectively associated with the risk of each lipid profile abnormality. METHODS: Subjects were nondiabetic Japanese, 40-55 years of age, who were not taking oral lipid-lowering medications: for the incidence of low high-density lipoprotein cholesterol (HDL-C), 7627 men with an HDL-C level ≥ 40 mg/dL; for high triglycerides, 6973 men with a triglyceride level <200 mg/dL; for high low-density lipoprotein cholesterol (LDL-C), 7273 men with an LDL-C level <160 mg/dL; for high non-HDL-C, 7415 men with a non-HDL-C level <190 mg/dL; and for high total cholesterol (TC), 7196 men with a TC level <240 mg/dL. Lipid profile abnormalities were defined according to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program. RESULTS: During the 6-year observation period, there were 1022 cases of low HDL-C. Multiple-adjusted hazard ratios for low HDL-C were 0.79 (95% confidence interval, 0.64-0.97) for sleep durations of 5 to <7 h and 0.62 (0.46-0.83) for ≥ 7 h compared with <5 h. There were 1473 cases of high triglycerides. Multiple-adjusted hazard ratios for high triglycerides were 0.81 (0.68-0.98) for sleep durations of 5 to <7 h and 0.90 (0.72-1.13) for ≥ 7 h compared with <5 h. However, no association between sleep duration and the risk of future high LDL-C, non-HDL-C, or TC was observed. CONCLUSIONS: Moderate and/or long sleep durations decreased the risk of future low HDL-C and high triglycerides.

Serum butyrylcholinesterase and the risk of future type 2 diabetes: the Kansai Healthcare Study.

OBJECTIVE: Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes. DESIGN: A prospective cohort study. PARTICIPANTS: A total of 8470 Japanese men aged 40-55 years without type 2 diabetes at baseline. MEASUREMENTS: Type 2 diabetes was diagnosed if a fasting plasma glucose (FPG) level was ≥7·0 mmol/l, if a HbA1 c level was ≥6·5% or if participants were taking oral hypoglycaemic medication or insulin. RESULTS: During the 42,227 person-years of follow-up, 868 cases had developed type 2 diabetes. Serum butyrylcholinesterase was significantly positively correlated with body mass index (BMI), FPG, alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and triglycerides (TG), whereas negatively with high-density lipoprotein (HDL) cholesterol. In Cox proportional hazards models, after adjusting for age, BMI, FPG, alcohol consumption, smoking habit, walk to work, regular leisure-time physical activity and family history of diabetes, the highest quartile (398-806 IU/l) of serum butyrylcholinesterase increased the risk of type 2 diabetes compared with the lowest quartile (56-311 IU/l) [hazard ratio (HR) 1·41 (95% confidence interval (CI), 1·14-1·74)]. After further adjusting for ALT and GGT, this association remained [HR 1·40 (95% CI, 1·13-1·73)]. Furthermore, this association was significant independent of TG and HDL cholesterol. CONCLUSIONS: Elevated serum butyrylcholinesterase was independently associated with an increased risk of future type 2 diabetes.

Relationship between drinking patterns and the risk of type 2 diabetes: the Kansai Healthcare Study.

BACKGROUND: Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed. METHODS: Study participants included 10 631 Japanese men aged 40-55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was ≥7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires. RESULTS: During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4-7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1-2.0 or 2.1-4.0 US standard drinks per drinking day on 4-7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers. CONCLUSIONS: More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4-7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers.

Cigarette smoking and the association with glomerular hyperfiltration and proteinuria in healthy middle-aged men.

BACKGROUND AND OBJECTIVES: Glomerular hyperfiltration and albuminuria accompanied by early-stage diabetic kidney disease predict future renal failure. Cigarette smoking has reported to be associated with elevated GFR in cross-sectional studies and with renal deterioration in longitudinal studies. The degree of glomerular hyperfiltration and proteinuria associated with smoking, which presumably is a phenomenon of early renal damage, has not been investigated in a satisfying manner so far. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 10,118 Japanese men aged 40 to 55 years without proteinuria or renal dysfunction at entry. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was defined as estimated GFR ≥117.0 ml/min per 1.73 m(2), which was the upper 2.5th percentile value of estimated GFR in the total population. Proteinuria was detected using standard dipstick. RESULTS: During the 6-year observation period, there were 449 incident cases of glomerular hyperfiltration and 1653 cases of proteinuria. Current smokers had a 1.32-time higher risk for the development of glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than nonsmokers after adjustment for baseline age, body mass index, systolic and diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular leisure-time physical activity, and estimated GFR. Both daily and cumulative cigarette consumption were associated with an increased risk for glomerular hyperfiltration and proteinuria in a dose-response manner. CONCLUSIONS: In middle-aged Japanese men, smoking was associated with an increased risk of glomerular hyperfiltration and dipstick proteinuria. Of importance, past smokers did not exhibit any increased risk for these conditions.

Elevated white blood cell count worsens proteinuria but not estimated glomerular filtration rate: the Kansai Healthcare Study.

BACKGROUND/AIMS: No prospective studies have estimated the association between white blood cell (WBC) count and the risk of proteinuria. We prospectively examined the relationships of WBC count, as a marker of inflammation, with two outcomes: proteinuria and low estimated glomerular filtration rate (eGFR). METHODS: We enrolled 10,008 Japanese men aged 40-55 years who had neither proteinuria nor low eGFR and were not taking antihypertensive medications at entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was defined if eGFR was <60 ml/min/1.73 m(2). RESULTS: During the 49,644 person-years of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age, body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure-time physical activity and eGFR, the highest quintile (≥7.51 × 10(3)/µl) of WBC count was independently associated with an increased risk of incidence of proteinuria [HR: 1.45 (95% CI: 1.23-1.73)] compared with the lowest quintile (≤4.80 × 10(3)/µl). On the other hand, during 52,833 person-years, we confirmed 439 cases of low eGFR. In multivariate models, there was no association between WBC count and low eGFR. CONCLUSION: Elevated WBC count was independently associated with an increased risk of proteinuria, but not low eGFR.

Blood pressure components and risk for chronic kidney disease in middle-aged Japanese men: The Kansai Healthcare Study.

It is unclear which blood pressure (BP) components (that is, systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP)) are superior predictors of chronic kidney disease (CKD). Furthermore it is unclear whether the combination of SBP+DBP or PP+MAP is superior to any of these four individual BP components in predicting CKD. We enrolled 9928 Japanese men aged 40-55 years who had a normal estimated glomerular filtration rate (eGFR), no proteinuria and no history of cardiovascular disease and were not taking any antihypertensive medications at baseline. CKD was defined as an eGFR of <60 ml min(-1) per 1.73 m(2) using the modified diet in renal disease equation. ΔAkaike's information criterion (ΔAIC) was used to compare the BP components-added model to the model without them in a Cox proportional hazards model. During the 52 428 person-years of follow-up, there were 434 cases of CKD. Of all four BP components, the model including DBP- or MAP-alone had the highest values of ΔAIC (10.2 and 9.85, respectively). The PP-alone model had the lowest ΔAIC value (-1.48). The combination models including SBP+DBP (ΔAIC 8.42) or PP+MAP (8.42) were not superior to the models including DBP- or MAP-alone. These findings suggested that, of the four BP components, both DBP and MAP were the most useful predictors for subsequent incidence of CKD, but PP was not an important predictor. The combination model, including SBP+DBP or PP+MAP, was not superior to the models including DBP- or MAP-alone for predicting CKD.

Effectiveness and safety of 1-year ad libitum consumption of a high-catechin beverage under nutritional guidance.

BACKGROUND: It has been reported that a continuous intake of a catechin beverage will reduce body fat. Traditionally, improvement of eating and exercise habits has been the basis for prevention and reduction of obesity. In this study, we conducted a trial involving human subjects who ingested a catechin beverage for 1 year under nutritional guidance. METHODS: This study was conducted based on a comprehensive cohort design using a catechin beverage (containing 588 mg of tea catechins) and a control beverage (containing 126 mg of tea catechins). At both the start and the end of the trial, the subjects underwent an annual health check and computer tomography for measurement of their abdominal fat. In addition, a food intake survey was conducted and all subjects were provided nutritional guidance by a registered dietitian every 3 months. RESULTS: Data were analyzed using per protocol samples of 134 subjects (catechin group, n = 77; control group, n = 57). Body weight and body mass index were reduced significantly in the catechin group compared to the control group. Changes in body weight during the study period were -1.1 kg in the catechin group and 0.2 kg in the control group. In the catechin group, the visceral fat areas at the start of the trial were significantly correlated with the magnitude of fat reduction at the end of the trial. Under the guidance of a registered dietitian, subjects in the catechin group who showed a reduction in their fat-derived energy percentage during the test period tended to reduce more body weight than those with an increase in this percentage, although no difference in total energy intake was noted between the two groups. One-year ad libitum consumption of a catechin beverage posed no health risks and resulted in a reduction in body weight. CONCLUSIONS: An overall improvement in dietary habits might enhance the weight-reduction effect of the beverage.

Combined measurement of fasting plasma glucose and A1C is effective for the prediction of type 2 diabetes: the Kansai Healthcare Study.

OBJECTIVE: We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes. RESEARCH DESIGN AND METHODS: Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG >or=126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves. RESULTS: During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001). CONCLUSIONS: The combined measurement of FPG and A1C was effective for predicting type 2 diabetes.

Lower serum creatinine is a new risk factor of type 2 diabetes: the Kansai healthcare study.

OBJECTIVE: Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was >or=126 mg/dl or if participants were taking oral hypoglycemic medication or insulin. RESULTS: During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl. CONCLUSIONS: Lower serum creatinine increased the risk of type 2 diabetes.

Liver enzymes compared with alcohol consumption in predicting the risk of type 2 diabetes: the Kansai Healthcare Study.

OBJECTIVE: It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. RESEARCH DESIGN AND METHODS: The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. RESULTS: During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. CONCLUSIONS: GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes.