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.

Increment of absolute neutrophil count in the third trimester and increased risk of small-for-gestational-age birth: Hirakata Risk Associated with Pregnancy Assessment Research (HIRAPAR).

OBJECTIVE: Small-for-gestational-age (SGA) infants, who have growth restriction, have higher perinatal morbidity and mortality. Excessive inflammatory reaction such as neutrophil activation has been observed in pregnant women whose offspring had restricted fetal growth, but the association between white blood cell (WBC) counts and SGA birth has not yet been assessed. We therefore examined the association of WBC count and its change with the risk of SGA birth. STUDY DESIGN: We enrolled 2356 pregnant women who had full-term singleton delivery at a private maternity hospital in Hirakata, Japan. SGA was defined as under the 10th percentile of birthweight for gestational age, baby sex, and mother's parity according to the Japanese neonatal anthropometric charts renewed in 2010. Blood samples were measured in the first and third trimesters. We performed multiple logistic regression analysis to assess associations between total and differential WBC counts and SGA birth. RESULTS: Women with SGA birth tended to have higher total WBC count in the third trimester compared with women who did not have SGA birth. This tendency was not observed for total WBC count in the first trimester. After adjustment for age, height, body mass index at entry, smoking habit, weekly gestational weight gain, and pregnancy-induced hypertension, higher total WBC count in the third trimester was associated with an increased risk of SGA birth. Total WBC count in the first trimester did not show any significant association with SGA birth. The ratio of total WBC count in the third trimester to that in the first trimester was associated with SGA birth; the odds ratio for 1 unit increase was 3.02 (95% CI: 1.54-5.92). Regarding differential WBC counts in the third trimester, neutrophil count but not lymphocyte count was associated positively with SGA birth. CONCLUSIONS: Higher total WBC and absolute neutrophil counts in the third trimester were associated with SGA birth. In addition, greater ratio of increase in total WBC counts during pregnancy showed a positive association with the incidence of SGA birth. These associations may reflect a vicious cycle of inflammation and placental dysfunction as a cause of fetal growth restriction.

Gestational bodyweight gain among underweight Japanese women related to small-for-gestational-age birth.

AIM: The prevalence of underweight women, who have an increased risk for small-for-gestational-age (SGA) birth, is increasing in Japan. We examined the associations of pre-pregnancy body mass index and gestational weight gain (GWG) with SGA birth among Japanese women. MATERIAL AND METHODS: We conducted a prospective cohort study of 1391 women who delivered full-term singleton babies. SGA was defined as below the 10th percentile of birthweight at each gestational age, baby sex, and parity. We calculated the 5th percentile of birthweight in the same way for another threshold for SGA. According to pre-pregnancy body mass index, we divided the participants into three groups: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), and overweight and obese (≥25.0 kg/m(2)). RESULTS: SGA birth was observed most frequently among the underweight group (13.8%). Underweight was associated with an increased risk of SGA birth. The multiple-adjusted odds ratio for underweight was 1.96 (95% confidence interval, 1.23-3.11) compared with normal weight. Sufficient GWG reduced the incidence and the multiple-adjusted odds ratio for 1-kg increase of GWG was 0.86 (0.81-0.92). The same tendency was observed for the delivery of infants below the 5th birthweight percentile. Women with underweight and normal weight who had 9.0 kg or less of GWG had a significantly higher risk of SGA birth than women with normal weight who had 9.1-11.0 kg of GWG. CONCLUSIONS: Underweight and poor GWG were associated with a higher incidence of SGA birth. However, the incidence of SGA birth among underweight women was not increased significantly if they had sufficient GWG.

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.

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study.

Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35-5.16) for tertile 2, and 5.08 (2.48-10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men.

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.