Smoking Status and Premature Death Among Japanese Rural Community-Dwelling Persons.

Background: Smoking status is known to be an independent and significant predictor of health outcomes related to aging and plays a crucial role in overall mortality rates. This cohort study investigated the relationship between smoking status and survival outcomes over follow-up periods of 9 and 21 years. Methods: The sample consisted of 3526 participants with a mean age of 64 ± 12 years, 44.1% of whom were male. The median follow-up duration was 6315 days, with an interquartile range of 3441 to 7727 days. Smoking status [i.e., Brinkmann index (BI)] was calculated by multiplying the number of years smoked by the number of cigarettes smoked daily. Based on this, participants were categorized into non-smokers, former smokers, and current smokers. The data were analyzed using Cox regression, employing age as the time variable and accounting for various risk factors. Results: A total of 1111 participants (49.2%) were confirmed to have died. Among these, 564 were male (36.2% of all male participants), and 547 were female (27.8% of all female participants). The multivariate-adjusted odds ratio (95% confidence interval) for all-cause mortality compared with never-smokers was 1.51 (1.17-1.96) for former smokers with BI > 800, 1.61 (1.20-2.17) for current smokers with BI of 400-799 and 1.62 (95% CI, 1.24-2.10) with BI of ≥800 (P for trend <0.001). Participants who died within three years of follow-up were excluded to avoid the possibility of reverse causation, but the results were essentially unchanged. Conclusion: We found that the BI is a valid predictor of future mortality risk and that BI 800 for former smokers and BI 400 for current smokers were useful cutoff values. Efforts to control smoking should focus not only on current smokers but also on former smokers to reduce the risk of premature death associated with smoking.

Association Between Tongue Pressure and Prevalence of Mild Cognitive Impairment in Japan.

OBJECTIVE: Although it has been suggested that a decline in oral function is one of the potential risk factors affecting mild cognitive impairment (MCI), evidence is insufficient to draw clear conclusions. This Japanese cross-sectional study examined the association between tongue pressure (TP) and MCI in middle-aged and older adults aged 36-84 years. METHODS: Study participants were 1019 (368 men and 651 women). TP was evaluated using a TP measurement device. The maximum value of three measurements was used for analysis. MCI was defined as being present if a participant had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, smoking status, alcohol consumption, leisure-time physical activity, body mass index, hypertension, dyslipidemia, diabetes mellitus, history of depression, number of teeth, employment, education, and household income. RESULTS: The prevalence of MCI was 45.3%. Among women, compared with the lowest tertile of TP, the second and highest tertiles were significantly associated with a lower prevalence of MCI with a clear dose-response relationship; the adjusted odds ratio (95% confidence intervals) in the second and highest tertiles of TP were 0.54 (0.36-0.83) and 0.55 (0.36-0.84), respectively (p for trend = 0.005). In contrast, no statistically significant association was observed between TP and the prevalence of MCI among men. CONCLUSIONS: Our findings suggest that higher TP might be inversely associated with the prevalence of MCI in middle-aged and older Japanese women.

Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Smoking and secondhand smoke exposure and carotid intima-media thickness: Baseline data from the Aidai Cohort Study in Japan.

INTRODUCTION: Epidemiological evidence regarding the relationship between smoking and secondhand smoke (SHS) exposure and carotid intima-media thickness (CIMT) has been limited in Asian populations. Employing baseline data from the Aidai Cohort Study, Japan, we evaluated the evidence in this cross-sectional study. METHODS: Study subjects were 727 men aged 35-88 years and 1297 women aged 34-85 years. Information on smoking, SHS exposure, and confounders was obtained through a self-administered questionnaire. An automated carotid ultrasonography device was used to measure the right and left CIMT. The greatest CIMT measurement in the left or right common carotid artery was considered the maximum CIMT, and a maximum CIMT >1.0 mm was indicative of carotid wall thickening. Age, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, and education level were adjusted at one time. RESULTS: The prevalence of carotid wall thickening was 13.0%. The prevalence of never smoking was 30.5% in men and 90.1% in women. Among those who had never smoked, the prevalence of never SHS exposure at home and work was 74.3% and 48.2% in men and 38.3% and 56.3% in women, respectively. Active smoking and pack-years of smoking were independently positively related to carotid wall thickening regardless of sex, although the association with current smoking in women was not significant. Independent positive relationships were shown between former smoking and pack-years of smoking and maximum CIMT in men but not in women. No significant relationships were found between SHS exposure at home and work and carotid wall thickening or maximum CIMT in either men or women. CONCLUSIONS: Active smoking, especially pack-years of smoking, was positively associated with carotid wall thickening in both sexes. Such positive associations with maximum CIMT were found only in men; however, interactions between smoking and sex were not significant.

Thigh-hip ratio is significantly associated with all-cause mortality among Japanese community-dwelling men.

Anthropometric evaluation is a simple yet essential indicator of muscle and fat mass when studying life prognosis in aging. This study aimed to investigate the contributions of anthropometric measurements, independent of body mass index, to measures of all-cause mortality. We examined data for 1,704 participants from the 2014 Nomura Cohort Study who attended follow-ups for the subsequent eight years (follow-up rate: 93.0%). Of these, 765 were male (aged 69 ± 11 years) and 939 were female (aged 69 ± 9 years). The Japanese Basic Resident Registry provided data on adjusted relative hazards for all-cause mortality. The data were subjected to a Cox regression analysis, wherein the time variable was age and the risk factors were gender, age, anthropometric index, smoking habits, drinking habits, exercise habits, cardiovascular history, hypertension, lipid levels, diabetes, renal function, and serum uric acid. Of the total number of participants, 158 (9.3%) were confirmed to have died, and of these, 92 were male (12.0% of all male participants) and 66 were female (7.0% of all female participants). The multivariable Cox regression analysis revealed that a smaller thigh-hip ratio predicted eight-year all-cause mortality in male participants, but only baseline body mass index was associated with all-cause mortality in female participants. Thigh-hip ratio is a useful predictor of death in Japanese community-dwelling men.

Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan.

OBJECTIVES: The relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single-nucleotide polymorphisms (SNPs) and diabetes mellitus (DM) has not been investigated. Therefore, we performed a case-control study to examine this relationship. METHODS: The study subjects included 2,390 Japanese men and women aged 34 to 88 years. In total, 190 cases were defined as having a fasting plasma glucose level ≥126 mg/dL, having a glycated hemoglobin ≥6.5% or currently using diabetic medication. The 2,200 remaining participants served as control subjects. RESULTS: Compared with study subjects with the CC genotype of AGXT2 SNP rs37369, those with the TT, but not CT, genotype had a significantly increased risk of DM: the adjusted odds ratio (OR) for the TT genotype was 1.83 (95% confidence interval [CI], 1.04 to 3.47). AGXT2 SNPs rs37370 and rs180749 were not significantly associated with the risk of DM. The CTA haplotype of rs37370, rs37369 and rs180749 was significantly positively associated with the risk of DM (crude OR, 1.25; 95% CI, 1.01 to 1.56), whereas the CCA haplotype was significantly inversely related to DM (crude OR, 0.53; 95% CI, 0.27 to 0.95). The multiplicative interaction between AGXT2 SNP rs37369 and smoking status with regard to the risk of DM was not significant (p=0.32 for interaction). CONCLUSIONS: This is the first study to show significant associations between AGXT2 SNP rs37369, the CTA haplotype, and the CCA haplotype and DM. No interaction with regard to the risk of DM was observed between rs37369 and smoking.

Hyperuricemia is associated with all-cause mortality among males and females: Findings from a study on Japanese community-dwelling individuals.

Background: Serum uric acid (SUA) is a key determinant of cardiovascular diseases (CVDs). Studies have also shown that SUA independently impacts age-related health outcomes, although their findings differ between males and females. Furthermore, predictive data on all-cause mortality remain limited, particularly for the Japanese population. Thus, this study examined the association between SUA and survival prognosis among males and females based on a follow-up period of 7 or 19 years. Methods: The study was based on 1,573 male (63 ± 14 years) and 1,980 female (65 ± 12 years) participants who participated in a Nomura Cohort Study in 2002 (Cohort 1) and 2014 (Cohort 2), and continued throughout the follow-up period. A basic resident register was referenced to derive the adjusted relative risk estimates for all-cause mortality. Finally, a Cox proportional hazards model analysis was conducted and was adjusted for possible confounders to estimate hazard ratios (HRs). 95% confidence intervals (CIs) were computed separately for male and female participants. Results: Of the total 3,553 participants, 905 (25.5%) were deceased. Of these, 473 were male (30.1% of all males) and 432 were female (21.8% of all females). Hyperuricemia was defined in males with SUA levels of 8.5 mg/dL or higher, and in females with SUA levels of 7.5 mg/dL or higher, and was associated with a significantly increased HR for all-cause mortality (males: 1.67; 95% CI: 1.06-2.63; females: 2.17; 95% CI: 1.20-3.94). The data were further stratified based on age (< 65 years or ≥ 65 years), body mass index (BMI) (< 25.0 kg/m2 or ≥ 25.0 kg/m2), History of cardiovascular disease, estimated glomerular filtration rate (< 60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2), and presence of SUA-lowering medication. All stratified groups demonstrated a similar trend. The hyperuricemia group in particular reported a significant increase in HR. On the other hand, a U-shaped increase in HR was observed in those with BMI greater than 25 kg/m2 and SUA-lowering medication, but interaction effect was not significant. Conclusions: Hyperuricemia is a key risk indicator for all-cause mortality in male and female community-dwelling individuals in Japan.

Low density lipoprotein cholesterol and all-cause mortality rate: findings from a study on Japanese community-dwelling persons.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up. METHODS: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD. RESULTS: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m2, and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015). CONCLUSIONS: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant.

Clubbed Digits Presumably Caused by Lubiprostone.

Digital clubbing has been regarded as an important sign in medicine. A 33-year-old woman with no history of hepatic, pulmonary, or malignant disease was referred to our hospital. She had been taking lubiprostone every day for three years for constipation. Clubbing in her upper and lower limb digits began gradually about two years ago. The results of laboratory investigations were almost normal. We suspected the clubbed digits were a side effect of lubiprostone and confirmed that the levels of urinary prostaglandin E2 (PGE2), which can cause clubbed digits, were elevated. Thus, we instructed the woman to stop taking lubiprostone and monitored this lab value. However, the value continued to rise over 2 months to 41.9 µg/g Cr. During that time, she had been taking sennoside A B calcium instead of lubiprostone for constipation. Since sennoside A B calcium also has the effect of increasing PGE2, we ordered the discontinuation. Her urinary PGE2 to creatinine level normalized, and the clubbing improved after the discontinuation of these two medications.

Thigh circumference and handgrip strength are significantly associated with all-cause mortality: findings from a study on Japanese community-dwelling persons.

PURPOSE: In addition to playing a critical role in cardiovascular health, muscle mass and strength independently impact aging-related health outcomes in adults. There are limited predictive data for all-cause mortality, particularly for community-dwelling persons in Japan. This study examined whether handgrip strength (HGS) and thigh circumference are related to survival prognosis based on a 6-year follow-up period. METHODS: Participants were 787 men (aged 69 ± 11 years) and 963 women (aged 69 ± 9 years) who took part in a Nomura cohort study conducted in 2014 and who continued with follow-ups for the subsequent 6 years (follow-up rate: 95.5%). We obtained adjusted relative hazards of all-cause mortality from the basic resident register. The data were subjected to a Cox regression with age as the time variable and gender, age, anthropometric index, smoking habits, drinking habits, exercise habits, cardiovascular history, blood pressure, lipid levels, diabetes, renal function, and serum uric acid as risk factors. RESULTS: Of the 1750 participants, a total of 97 (5.5%) were confirmed to have died, of which 56 were men (7.1% of all male participants), and 41 were women (4.3% of all female participants). The multivariable Cox regression analysis revealed that smaller thigh circumference and lower HGS in men were found to predict 6-year all-cause mortality, but in women only baseline HGS was associated with all-cause mortality. CONCLUSION: Thigh circumference and HGS are useful predictors of death in Japanese community-dwelling men.

Increased body mass index above the upper normal limit is significantly associated with renal dysfunction among community-dwelling persons.

PURPOSE: Body mass index (BMI) is a simple index of weight-to-height that is commonly used to classify people as underweight, overweight or obesity, and high BMI has been clearly linked to increased risk of illness in adults. However, few studies have examined the significance of upper normal weight as a risk factor for the development of chronic kidney disease (CKD) in the general Japanese population. METHODS: We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 421 men aged 67 ± 10 (mean ± standard deviation; range 24-95) years and 565 women aged 68 ± 9 (22-84) years during their annual health examination in a single community. We examined the relationship between quartiles of baseline BMI and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations modified by the Japanese coefficient. CKD was defined as having dipstick-positive proteinuria (≥ 1 +) or a low eGFR (< 60 mL/min/1.73 m2). RESULTS: Of the 986 participants, a total of 134 (13.6%) participants, including 72 (17.1%) men and 62 (11.0%) women, received a new diagnosis of CKD during the study period, and 25 (9.7%), 19 (8.0%), 47 (19.0%), and 43 (17.8%) diagnoses were received in the BMI-1 (BMI, < 20.7 kg/m2), BMI-2 (BMI, 20.7 to 22.5 kg/m2), BMI-3 (BMI, 22.6 to 24.4 kg/m2), and BMI-4 (BMI ≥ 24.5 kg/m2) groups, respectively. Using BMI-2 as the reference group, the non-adjusted odds ratio (OR) (95% confidence interval) for CKD was 2.70 (1.53-4.75) for BMI-3 and 2.49 (1.40-4.42) for BMI-4, and the multivariable-adjusted OR was 2.52 (1.40-4.56) for BMI-3 and 2.30 (1.26-4.22) for BMI-4. CONCLUSIONS: Increased BMI from upper normal weight is strongly associated with the development of CKD in community-dwelling persons.

Metabolic syndrome is a predictor of decreased renal function among community-dwelling middle-aged and elderly Japanese.

PURPOSE: Metabolic syndrome (MetS) is increasing worldwide with the continuous increase in obesity prevalence. Chronic kidney disease (CKD) is also a major public health problem, but there is controversy over whether baseline MetS is a predictor of decreased renal function among Japanese community-dwelling middle-aged and elderly Japanese. METHODS: We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 410 men aged 68 ± 8 (mean ± standard deviation; range, 50-95) years and 549 women aged 69 ± 7 (50-84) years during their annual health examination in a single community. We examined the relationship between baseline MetS and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFRCKDEPI) using the CKD-EPI equations modified by the Japan coefficient. CKD was defined as dipstick-positive proteinuria (> or = 1 +) or a low eGFRCKDEPI (< 60 mL/min/1.73 m2). RESULTS: Of the 959 participants, 413 (43.1%) had MetS at baseline. Annual eGFR decline rate was significantly greater in those with MetS than in those without MetS, and the annual eGFR decline rate of < - 1.2 mL/min/1.73 m2/year increased significantly in relation to presence of baseline MetS, especially low HDL cholesterol (HDL-C). Moreover, the incidence rate of CKD after 3 years was 13.5% and increased significantly in relation to presence of baseline MetS, especially its components such as elevated HbA1c. The multivariate-adjusted odd ratio (OR) for CKD in participants with MetS versus those without MetS was 1.55 (0.99-2.43). The multivariate-adjusted ORs for rapid annual eGFR decline rate were significantly high in patients aged ≥ 65 years and presence of medication, regardless of gender and eGFR value. CONCLUSIONS: Low HDL-C and elevated HbA1c levels correlated significantly with eGFR decline in a short period of 3 years. MetS also showed a significant association with eGFR decline. This study suggests the importance of low HDL-C and elevated HbA1c in the effect of MetS on eGFR decline rather than obesity among Japanese community-dwelling middle-aged and elderly Japanese without CKD.

Neutrophil to Lymphocyte Ratio is a Predictive Factor of Malignant Potential for Intraductal Papillary Mucinous Neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 (P = .001), prognostic nutritional index (PNI) < 45 (P = .016), CA 19-9 > 37 U/mL (P = .039), and cystic diameter ⩾ 30 mm (P = .010), and mural nodule (P = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1.

Usefulness of waist-to-height ratio in screening incident metabolic syndrome among Japanese community-dwelling elderly individuals.

This study examined a range of anthropometric indices and their relationships with metabolic syndrome (MetS). Despite recommendations that central obesity assessment should be employed as a marker of metabolic health, there is no consensus regarding the protocol for measurement. The present study included 720 men aged 71 ± 8 years and 919 women aged 71 ± 7 years from a rural village. We examined the relationship between anthropometric indices {e.g., body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHpR)}, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report in a cross-sectional (N = 1,639) and cohort (N = 377) data. A receiver operating curve (ROC) analysis was performed to determine the optimal cut-off value and best discriminatory value of each of these anthropometric indices to predict MetS. In the cross-sectional study, WHtR as well as BMI and WHpR showed significantly predictive abilities for MetS in both genders; and WHtR showed the strongest predictive ability for the presence of MetS. Also in the cohort study, WHtR as well as BMI and WHpR showed significantly predictive abilities for incident MetS in both genders, and in men WHtR showed the strongest predictive ability for incident MetS, but in women BMI showed the strongest predictive ability. In the cross-sectional study, the optimal WHtR cutoff values were 0.52 (sensitivity, 71.0%; specificity, 77.9%) for men and 0.53 (sensitivity, 79.8%; specificity, 75.7%) for women. In the cohort study, the optimal WHtR values were 0.50 (sensitivity, 60.7%; specificity, 73.2%) for men and 0.50 (sensitivity, 75.0%; specificity, 56.1%) for women. Increased WHtR was significantly and independently associated with prevalence of MetS in both genders. These results suggest that WHtR is a useful screening tool for determining metabolic risk in Japanese elderly community dwelling individuals.

Association of neutrophil-to-lymphocyte ratio with early renal dysfunction and albuminuria among diabetic patients.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in diabetic kidney disease is not yet established. METHODS: The subjects comprised 199 men aged 73 ± 11 (mean ± standard deviation) years and 187 women aged 77 ± 10 years from a rural hospital. We examined the relationship between NLR calculated by analyzing differential leukocyte count in complete blood picture and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation and urinary albumin excretion (UAE). RESULTS: NLR was negatively related to eGFR and positively related to UAE. Multiple linear regression analysis using eGFR and UAE as an objective variables, adjusted for confounding factors as explanatory variables showed that NLR (ß = - 0.101, p = 0.009) as well as age, body mass index, serum uric acid, and presence of uric acid lowing medication were significantly and independently associated with eGFR, and NLR (ß = 0.113, p = 0.031) as well as prevalence of cardiovascular disease, systolic blood pressure, presence of antihypertensive medication, presence of antilipidemic medication, and eGFR were significantly and independently associated with UAE. The multivariate-adjusted odds ratios (95% confidence interval) of NLR for stage 3a (eGFR < 60 mL/min/1.73 m2), stage 3b (eGFR < 45 mL/min/1.73 m2), and microalbuminuria (UAE ≥ 30 mg/g Cr) were 1.90 (1.02-3.56) and 2.99 (1.28-6.98), and 1.77 (1.04-3.01), respectively. Next, to examine the consistency of the observed association between NLR and eGFR, we performed subgroup analyses. There was a significant interaction (p = 0.006) only between the two groups regarding antihypertensive medication (absence: ß = - 0.272, p < 0.001 and presence: ß = - 0.029, p = 0.564). CONCLUSIONS: Our data suggested that NLR might be important as a potential factor for evaluating patients with a higher degree of albuminuria among diabetic outpatients.

Mildly elevated serum total bilirubin is negatively associated with hemoglobin A1c independently of confounding factors among community-dwelling middle-aged and elderly persons.

Abnormally high glycated hemoglobin (Hb) (HbA1c) is significantly associated with oxidative stress and an increased risk of cardiovascular disease (CVD). Serum total bilirubin (T-B) may have a beneficial role in preventing oxidative changes and be a negative risk factor of CVD. Limited information is available on whether serum T-B is an independent confounding factor of HbA1c. The study subjects were 633 men aged 70 ± 9 (mean ± standard deviation (SD)) years and 878 women aged 70 ± 8 years who were enrolled consecutively from among patients aged ≥40 years through a community-based annual check-up process. We evaluated the relationship between various confounding factors including serum T-B and HbA1c in each gender. Multiple linear regression analysis pertaining to HbA1c showed that in men, serum T-B (ß = -0.139) as well as waist circumference (ß = 0.099), exercise habit (ß = 0.137), systolic blood pressure (SBP) (ß = 0.076), triglycerides (ß = 0.087), and uric acid (ß = -0.123) were significantly and independently associated with HbA1c, and in women, serum T-B (ß = -0.084) as well as body mass index (ß = 0.090), smoking status (ß = -0.077), SBP (ß = 0.117), diastolic blood pressure (DBP) (ß = -0.155), low-density lipoprotein cholesterol (ß = 0.074), prevalence of antidyslipidemic medication (ß = 0.174), and uric acid (ß = 0.090) were also significantly and independently associated with HbA1c. Multivariate-adjusted serum HbA1c levels were significantly high in subjects with the lowest serum T-B levels in both genders. Serum T-B is an independent confounding factor for HbA1c among community-dwelling middle-aged and elderly persons.

Dual Effects of a RETN Single Nucleotide Polymorphism (SNP) at -420 on Plasma Resistin: Genotype and DNA Methylation.

CONTEXT: We previously reported that single nucleotide polymorphism (SNP)-420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of cytosine-phosphate-guanine dinucleotides. OBJECTIVE: To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420. DESIGN AND METHODS: Genomic DNA was extracted from peripheral white blood cells in 2078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after DNA bisulfite conversion. RESULTS: Methylation at SNP-420 was highest in the C/C genotype (36.9 ± 5.7%), followed by C/G (21.4 ± 3.5%) and G/G (2.9 ± 1.4%; P < 0.001). When assessed in each genotype, methylation at SNP-420 was inversely associated with plasma resistin in the C/C (ß = -0.134, P < 0.001) or C/G (ß = -0.227, P < 0.001) genotype. In THP-1 human monocytes intrinsically having the C/C genotype, a demethylating reagent, 5-aza-dC, decreased the methylation at SNP-420 and increased RETN messenger RNA. SNP+1263 (rs3745369), located in the 3' untranslated region of RETN, was also associated with methylation at SNP-420. In addition, highly sensitive C-reactive protein was inversely associated with methylation at SNP-420 in the C/C genotype, whereas body mass index was positively associated. CONCLUSIONS: Plasma resistin was inversely associated with the extent of methylation at SNP-420 mainly dependent on the SNP-420 genotype. The association can also be explained partially independent of SNP-420 genotypes. SNP-420 could have dual, genetic and epigenetic effects on plasma resistin.

Gender difference in preference of specialty as a career choice among Japanese medical students.

BACKGROUND: In Japan, the absolute deficiency of doctors and maldistribution of doctors by specialty is a significant problem in the Japanese health care system. The purpose of this study was to investigate the factors contributing to specialty preference in career choice among Japanese medical students. METHODS: A total of 368 medical students completed the survey giving an 88.2 % response rate. The subjects comprised 141 women aged 21 ± 3 (range, 18-34) years and 227 men aged 22 ± 4 (range, 18-44) years. Binary Logistic regression analysis was performed using specialty preferences as the criterion variable and the factors in brackets as six motivational variables (e.g., Factor 1: educational experience; Factor 2: job security; Factor 3: advice from others; Factor 4: work-life balance; Factor 5: technical and research specialty; and Factor 6: personal reasons). RESULTS: Women significantly preferred pediatrics, obstetrics & gynecology, and psychology than the men. Men significantly preferred surgery and orthopedics than the women. For both genders, a high odds ratio (OR) of "technical & research specialty" and a low OR for "personal reasons" were associated with preference for surgery. "Technical & research specialty" was positively associated with preference for special internal medicine and negatively for pediatrics. "Work-life balance" was positively associated with preference for psychology and negatively for emergency medicine. Among the women only, "technical & research specialty" was negatively associated with preference for general medicine/family medicine and obstetrics & gynecology, and "job security" was positively associated for general medicine/family medicine and negatively for psychology. Among men only, "educational experience" and "personal reasons" were positively, and "job security" was negatively associated with preference for pediatrics. For both genders, "work-life balance" was positively associated with preference for controllable lifestyle specialties. CONCLUSION: We must acknowledge that Japanese medical students have dichotomized some motivations for their specialty preference based on gender. Systematic improvements in the working environment are necessary to solve these issues.

Handgrip Strength Is Positively Associated with Mildly Elevated Serum Bilirubin Levels among Community-Dwelling Adults.

Handgrip strength (HGS) is a useful measure of health-related quality of life and general muscle strength. Serum total bilirubin (T-B) may present potential beneficial effects in preventing oxidative changes which are associated with a risk of metabolic syndrome and the development of cardiovascular disease. Limited information is available regarding whether HGS is an independent confounding factor for serum T-B. The study participants were 214 men aged 71 ± 8 (mean ± standard deviation) years and 302 women aged 71 ± 7 years that were enrolled consecutively from among paticipants aged ≥ 50 years through an annual check-up process. We evaluated the relationship between serum T-B and confounding factors within each sex. HGS related significantly with serum T-B in both men (r = 0.156, p = 0.023) and women (r = 0.173, p = 0.003). Multiple linear regression analysis showed that in men, HGS (ß = 0.173) as well as smoking status (ß = -0.147), exercise habit (ß = 0.138), low-density lipoprotein cholesterol (ß = 0.146), and hemoglobin A1c (HbA1c) (ß = -0.198) were significantly and independently associated with serum T-B. In women, HGS (ß = 0.159) as well as smoking status (ß = -0.116), high-density lipoprotein cholesterol (ß = 0.159), and HbA1c (ß = -0.161) were significantly and independently associated with serum T-B. Multivariate-adjusted serum T-B levels were significantly lower in subjects with the lowest HGS level in both sexes. Increased HGS is strongly associated with increased serum T-B, independent of confounding factors in both sexes.

Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population.

Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and -358 (rs3219175) located in the human resistin gene (RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP -358 G>A, followed by rs1423096 C>T, SNP -420 C>G, and rs10401670 C>T (P = 5.39×10-47, 1.81×10-22, 2.09×10-16, and 9.25×10-15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3'-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP-420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population.