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Background: Prioritization for novel coronavirus disease 2019 (COVID-19)-related health policies usually considers age and certain other characteristics, but sex is rarely included, despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men versus women is the same.Methods: We analyzed 23,414 Japanese COVID-19 inpatients aged 20-89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation/invasive mechanical ventilation/extracorporeal membrane oxygenation/ death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model.Results: The odds ratio (OR) of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 (95% CI, 2.44-3.12), 2.78 (95% CI, 2.42-3.19), and 2.60 (95% CI, 2.23-3.03), respectively, after adjustment for age and date of admission. These risks for men were equivalent to those for women 14.1 (95% CI, 12.3-15.8), 11.2 (95% CI, 9.7-12.8), and 7.5 (95% CI, 6.3-8.7) years older, respectively.Conclusion: The risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.

The activation of α adrenergic receptors contributes to analgesia not only in the central nervous system but also in the peripheral nervous system. We reported that noradrenaline inhibits the activity of transient receptor potential vanilloid 1 (TRPV1) evoked by capsaicin through α receptors in cultured rat dorsal root ganglion (DRG) neurons. However, it is unclear whether activation of TRPV1 expressed in peripheral nerve terminals is inhibited by α receptors and whether this phenomenon contributes to analgesia. Therefore, we examined effects of clonidine, an α receptor agonist, on several types of nociceptive behaviors, which may be caused by TRPV1 activity, and subtypes of α receptors expressed with TRPV1 in primary sensory neurons in rats. Capsaicin injected into hind paws evoked nociceptive behaviors and clonidine preinjected into the same site inhibited capsaicin-evoked responses. This inhibition was not observed when clonidine was injected into the contralateral hind paws. Preinjection of clonidine into the plantar surface of ipsilateral, but not contralateral, hind paws reduced the sensitivity to heat stimuli. Clonidine partially reduced formalin-evoked responses when it was preinjected into ipsilateral hind paws. The expression level of α receptor mRNA quantified by real-time PCR was highest followed by those of α and α receptors in DRGs. α and α receptor-like immunoreactivities were detected with TRPV1-like immunoreactivities in the same neurons. These results suggest that TRPV1 and α receptors are coexpressed in peripheral nerve terminals and that the functional association between these two molecules causes analgesia.

OBJECTIVE: In type 2 diabetes, the significant pathological change in pancreatic islets is amyloid deposits. Its major component is islet amyloid polypeptide (IAPP). The objective of this study was to evaluate the possibility that the effect of the IAPP genotype on β-cell dysfunction in type 2 diabetes is modified by variations in plasma glucose levels. METHODS: Participants from the Toon Genome Study underwent a 75 g OGTT for the diagnosis of glucose tolerance and the evaluation of insulin secretion. We examined the effect of a SNP, rs77397980, on β-cell function by analyzing an interaction (statistics) between the IAPP genotype and AUC glucose. RESULTS: The ratio of the C-allele carriers was essentially the same among subjects with normal glucose tolerance, impaired glucose tolerance and diabetes. In subjects with diabetes, along with an increase in AUC glucose, fasting insulin remained constant in the T/T homozygotes and appeared to decrease in the C-allele carriers. A homeostasis model assessment (HOMA)-IR appeared to be increased in the former and decreased in the latter. In subjects with diabetes stratified into cases with higher AUC glucose than the median, fasting insulin and HOMA-IR were lower in the C-allele carriers than in the T/T homozygotes. An interaction between the IAPP genotype and AUC glucose was indicated in the effect on HOMA-IR. CONCLUSIONS: The possibility that the association between IAPP genotype and basal insulin level is modified by variation in plasma glucose, resulting in a decreased basal insulin in type 2 diabetes, cannot be excluded. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00523-4.

Background The collection of weighed food records (WFR) is a gold standard for dietary assessment. We propose using the 24-h recall method combined with a portable camera and a food atlas (24hR-camera). This combination overcomes the disadvantages of the 24-h dietary recall method. Our study examined the validity of the 24hR-camera method against WFR by comparing the results. Methods Study subjects were 30 Japanese males, aged 31–58 years, who rarely cook and reside in the Tokyo metropolitan area. For validation, we compared the estimated food intake (24hR-camera method) and weighed food intake (WFR method). The 24hR-camera method uses digital photographs of all food consumed during a day, taken by the subjects, and a 24-h recall questionnaire conducted by a registered dietitian, who estimates food intake by comparing the participant’s photographs with food atlas photographs. The WFR method involves a registered dietitian weighing each food item prepared for the subject to consume and any leftovers. Food intake was calculated for each food group and nutrient using the 24hR-camera vs. weighed methods. Results Correlation coefficients between the estimated vs. weighed food intake were 0.7 or higher in most food groups but were low in food groups, such as oils, fats, condiments, and spices. The estimated intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, the percentages of the mean difference between estimated vs. weighed food intake were -22.1% to 5.5%, with no significant differences between the methods (except for algae, which had a very low estimated intake). The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the macronutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation coefficients: greater than 0.75. The correlation coefficients between the estimated vs. weighed for salt equivalents and potassium intake were 0.583 and 0.560, respectively, but no significant differences in intake were observed. Conclusions The 24hR-camera method satisfactorily estimated the intake of energy and macronutrients (except salt equivalents and potassium) in Japanese males and was confirmed as a useful method for dietary assessment.

Purpose: Increased use of deep learning (DL) in medical imaging diagnoses has led to more frequent use of 10-fold cross-validation (10-CV) for the evaluation of the performance of DL. To eliminate some of the (10-fold) repetitive processing in 10-CV, we proposed a "generalized fitting method in conjunction with every possible coalition of N-combinations (G-EPOC)", to estimate the range of the mean accuracy of 10-CV using less than 10 results of 10-CV. Material and methods: G-EPOC was executed as follows. We first provided (2N-1) coalition subsets using a specified N, which was 9 or less, out of 10 result datasets of 10-CV. We then obtained the estimation range of the accuracy by applying those subsets to the distribution fitting twice using a combination of normal, binominal, or Poisson distributions. Using datasets of 10-CVs acquired from the practical detection task of the appendicitis on CT by DL, we scored the estimation success rates if the range provided by G-EPOC included the true accuracy. Results: G-EPOC successfully estimated the range of the mean accuracy by 10-CV at over 95% rates for datasets with N assigned as 2 to 9. Conclusions: G-EPOC will help lessen the consumption of time and computer resources in the development of computer-based diagnoses in medical imaging and could become an option for the selection of a reasonable K value in K-CV.

The activation of α2 adrenergic receptors contributes to analgesia not only in the central nervous system but also in the peripheral nervous system. We reported that noradrenaline inhibits the activity of transient receptor potential vanilloid 1 (TRPV1) evoked by capsaicin through α2 receptors in cultured rat dorsal root ganglion (DRG) neurons. However, it is unclear whether activation of TRPV1 expressed in peripheral nerve terminals is inhibited by α2 receptors and whether this phenomenon contributes to analgesia. Therefore, we examined effects of clonidine, an α2 receptor agonist, on several types of nociceptive behaviors, which may be caused by TRPV1 activity, and subtypes of α2 receptors expressed with TRPV1 in primary sensory neurons in rats. Capsaicin injected into hind paws evoked nociceptive behaviors and clonidine preinjected into the same site inhibited capsaicin-evoked responses. This inhibition was not observed when clonidine was injected into the contralateral hind paws. Preinjection of clonidine into the plantar surface of ipsilateral, but not contralateral, hind paws reduced the sensitivity to heat stimuli. Clonidine partially reduced formalin-evoked responses when it was preinjected into ipsilateral hind paws. The expression level of α2C receptor mRNA quantified by real-time PCR was highest followed by those of α2A and α2B receptors in DRGs. α2A and α2C receptor-like immunoreactivities were detected with TRPV1-like immunoreactivities in the same neurons. These results suggest that TRPV1 and α2 receptors are coexpressed in peripheral nerve terminals and that the functional association between these two molecules causes analgesia.

Summary Background & aims Increasing evidence has suggested a protective role of vitamin D on diabetes, but epidemiologic evidence is scarce among Asian populations. Here we prospectively examined the association between serum 25-hydroxyvitamin D3 (25[OH]D3) and type 2 diabetes (T2D) risk in Japanese individuals. Methods A nested case–control study was conducted in a biomarker cohort of 4754 employees (baseline age 34–69 years) who had attended in a comprehensive health checkup and donated a blood sample. Diabetes diagnosis was based on plasma glucose, glycated hemoglobin, and self-reporting during the 5-year follow-up. Using density sampling, two controls were randomly matched to each case by sex, age, and date of checkup; 336 cases and 668 controls had serum 25(OH)D3 data. Association between serum 25[OH]D3 and the risk of T2D was assessed using conditional logistic regression analysis. Results Serum 25(OH)D3 was significantly and inversely associated with T2D risk after adjustment for known risk factors other than BMI (OR [highest vs. lowest serum 25(OH)D3 quartile] = 0.58, 95% CI = 0.36–0.92; P for trend = 0.03). This association was somewhat attenuated after additional adjustment for BMI (OR = 0.65, 95% CI = 0.40–1.08; P for trend = 0.08). The inverse association was more evident among individuals whose blood samples were taken during the darker season (OR = 0.45; P for trend = 0.01). In the highest quartile of 25(OH)D3, progression from prediabetes to T2D was about 37% lower than in the lowest quartile. Conclusions Higher circulating 25(OH)D3 was associated with a lower risk of T2D, and this association was stronger among individuals whose blood was taken during the darker season and among those with prediabetes.

In the avian spinal cord, ten pairs of protrusions called accessory lobes (ALs) are located at both lateral sides of the lumbosacral spinal cords near the dentate ligament. It is predicted that ALs act as a sensory organ of equilibrium during bipedal walking. Previously, we demonstrated that cells isolated from chick ALs showed voltage-gated Na+ and K+ currents and action potentials using electrophysiological method. However, it is unclear which isoform of voltage-gated sodium channel (VGSC) are expressed in ALs and whether cells having neuronal morphology in ALs express VGSCs. To clear up these points, we performed RT-PCR and immunohistochemical experiments. In ALs, the specific PCR products of Nav 1.1–1.7 were detected by RT-PCR analysis, and Nav 1.1 and 1.6 isoforms showed strong intensities among them. In immunohistochemical experiments, cytoplasm and/or cell membranes of the AL contained cells having neuron-like morphology were stained by anti-VGSC antibody and filament-like structure showed GFAP-like immunoreactivity. The VGSC- and GFAP-like immunoreactivities did not overlap. These results show that neuronal-type VGSCs are mainly expressed and that neuron-like morphology cells express VGSCs in the ALs. Our present and previous findings indicate that AL neurons generate action potentials and support the hypothesis that ALs act as organ sensing body balance during walking on the ground., 第99回日本生理学会大会

The associations between the types/amounts of beverages consumed in daily life and measures of the glycemia status were investigated in a Japanese population-based cohort.Data from the baseline survey of the Japan Public Health Center-based Prospective Diabetes cohort were used. A cross-sectional analysis was performed in 3852 men and 6003 women who were evaluated under the fasting condition. The daily consumptions of coffee, green tea, oolong tea, black tea, soft drinks, fruit juices, or plain water were assessed using a self-reported questionnaire. Multivariable-adjusted linear regression analyses were performed using measures of the glycemia status (fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) ) as dependent variables and the types/amounts of beverages consumed as the independent variables, to calculate the differences according to the types/amounts of beverages consumed.In the multivariable-adjusted models, coffee consumption of ≥240 mL/day was significantly associated with a change of the FPG level by -1.9 mg/dL in men (p = 0.013) and -1.4 mg/dL in women (p = 0.015), as compared to coffee consumption of 0 mL/day. No significant association of the FPG level was observed with any of the other types/amounts of beverages consumed. On the other hand, significant associations were found between the HbA1c levels and consumption of several types of beverages.High coffee consumption was associated with lower FPG levels in this Japanese population. Some unexpected associations of the HbA1c levels with the consumption of some types of beverages were observed, which need to be further investigated.

Background The aim of this study was to identify associations between smoking status and the severity of COVID-19, using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP), and to explore the reasons for the inconsistent results previously reported on this subject. Methods The analysis included 17 666 COVID-19 inpatients aged 20–89 years (10 250 men and 7416 women). We graded the severity of COVID-19 (grades 0 to 5) according to the most intensive treatment required during hospitalization. The smoking status of severe grades 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately of grade 5 (death) were compared with that of grade 0 (no oxygen, reference group) using multiple logistic regression. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities. Results Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, using grade 0 as a reference group, with age- and admission-date-adjusted ORs (95% CI) of 1.51 (1.18–1.93) and 1.65 (1.22–2.24), respectively. An additional adjustment for comorbidities weakened the ORs. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex. Conclusions The severity of COVID-19 was not associated with current or former smoking per se but with the comorbidities caused by smoking. Thus, smoking cessation is likely to be a key factor for preventing smoking-related disease and hence for reducing the risk of severe COVID-19.

Aims It is known that autonomic nerve activity (ANA) affects glucose metabolism by regulating the secretion of insulin and glucagon. Sympathetic nerve stimulation results in increased blood glucose levels. ANA also showed a circadian variation, and sympathetic nerve activity was minimal at night and began to rise at arousal. Therefore, a drastic alteration in ANA around wake-up would be associated with glycemic variability (GV) known risk factor for cardiovascular disease. We investigated the relation between ANA around wake-up and either morning or daily GV. Methods We simultaneously performed Holter ECG and continuous glucose monitoring system in 41 patients with type 2 diabetes (T2D). ANA was assessed by heart rate variability (HRV) analysis. Delta (Δ) wake-up was defined as the difference between the maximum and minimum value during 1 h before and after wake-up time, before breakfast. Results Δ of low frequency/high frequency (LF/HF) around wake-up time (Δ LF/HF wake-up) was positively associated with Δ glucose wake-up, standard deviation (SD) glucose wake-up, the mean amplitude of glucose excursions (MAGE24h), and SD glucose24h after adjustment for age, sex, BMI, the duration of diabetes, and the prevalence of diabetic polyneuropathy (β = 0.47, p = 0.011, β = 0.48, p = 0.009, β = 0.54, p = 0.002 and β = 0.41, p = 0.0025, respectively). No association was found between Δ LF/HFwake-up and either mean blood glucose for 24 h, or HbA1c as parameters of chronic hyperglycemia. Conclusions In T2D, the fluctuation in fasting sympathetic nerve activity around wake-up was positively associated with not only morning but also daily GV.

Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008–2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.

Aims The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. In this study, we verified which of HbA1c and fasting plasma glucose (FPG) is more effective for detecting the diabetic retinopathy longitudinally in a Japanese population. Materials and Methods The study subjects underwent health examinations twice (including eye test and questionnaire of lifestyle and health) in 2008‐2009 (baseline) and in 2012‐2013 (4‐year follow‐up). Both non‐DM and DM patients at baseline were included as the participants. Of these participants, who had not been diagnosed with retinopathy at the baseline survey (n = 2427; 2150 men and 277 women) had eye fundus photographs taken four years later (follow‐up survey). The odds ratios of incidence of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for sex and age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results The odds ratios (95% confidence intervals) of incidence of retinopathy by HbA1c level categories, in ascending order, were 1.0 (ref.), 5.66 (1.14‐28.26), 1.69 (0.24‐12.04), 3.03 (0.50‐18.28), 1.04 (0.09‐11.59), 4.73 (0.78‐28.69), 4.12 (0.74‐22.85) and 24.47 (5.61‐106.75). For both FPG and HbA1c levels, the odds ratio for the development of retinopathy increased linearly with the increases in the levels FPG and HbA1c, and no clear threshold was observed. The AUC values (SE) for FPG and HbA1c were almost the same, at 0.750 (0.046) and 0.732 (0.048). Conclusions It was clarified that the higher the level of FPG and HbA1c was, the higher the incidence of retinopathy after 4 years was. There was no clear threshold. The detection ability of the incidence of retinopathy was almost the same between FPG and HbA1c, suggesting it is possible to detect the risk of retinopathy by HbA1c only., A comparison in the ability to detect diabetic retinopathy between fasting plasma glucose and HbA1c levels in a longitudinal study.

Background The collection of weighed food records (WFR) is a gold standard for dietary assessment. However, what a person eats changes every day, and it is practically difficult to weigh foods and drinks daily and calculate their nutrient contents. The validity of 24-hour dietary recall with the use of a portable camera (24hR-camera) was examined by comparison with the WFR.Methods The study subjects were recruited from 30 male adults who were fathers of university students and cooked rarely. For the validation of the 24hR-camera, we compared it and the WFR. The digital photographs were taken by the subjects of all food consumed during a day and a 24-h recall questionnaire was conducted by a registered dietitian who was trained on the survey methodology. An estimate of the amount of food consumed was made using a food atlas and the photographs taken by the subjects. For validation, comparison was made between the calculations, by both methods, of the levels of food group and nutrient. Results Correlation coefficients between the two methods were 0.7 or higher in most food groups but were low in food groups that are difficult to see, such as oils, fats, condiments, and spices. The intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, except for algae, of which intake amount (in weight base) is very low, the percentages of mean difference between 24hR-camera and WFR s were -22.1% to 5.5%, with no significant differences between the methods. The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the three major nutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation with coefficients greater than 0.75. The correlation coefficients between the two methods were 0.583 and 0.560 for salt and potassium intake, respectively, but no significant differences in intake were observed. Conclusions The method of 24-hR-canera satisfactorily estimated the intake of energy and major nutrients (except salt and potassium) in Japanese males, and was confirmed as a useful method for dietary assessment.

Highlights • We examined the role of TRPV1 in the generation of spontaneous APs in NGF-treated cultured DRG neurons of rats. • Spontaneous firing in the on-cell configuration was abolished by TRPV1 antagonists capsazepine and BCTC. • Chronic treatment with NGF induced capsazepine- and BCTC-sensitive cation conductance. • NGF-induced cation conductance through TRPV1 causes spontaneous firing., Dorsal root ganglion (DRG) neurons cultured in the presence of nerve growth factor (NGF, 100 ng/ml) often show a spontaneous action potential. Underlying mechanisms of this spontaneous firing were examined using the patch clamp technique. The spontaneous firing in the on-cell configuration was abolished by a decrease in the Na+ concentration and by the TRPV1 antagonists capsazepine (10 μM) and BCTC (1 μM). These responses were accompanied by hyperpolarization of the resting potential. The holding current observed in neurons voltage clamped at –60 mV in the whole-cell configuration was significantly larger in the neurons that fired spontaneously, indicating that these neurons had an additional cation conductance that caused depolarization and triggered action potentials. The holding current in the firing neurons was decreased by extracellular Na+ reduction, capsazepine and BCTC. The amplitudes of the capsazepine- or BCTC-sensitive component of the holding current in the spontaneously firing neurons were ten times as large as those recorded in the other neurons showing no spontaneous firing. However, the amplitudes of the current responses to capsaicin (1 μM) were not different regardless of the presence of spontaneous firing or treatment with NGF. These results indicate that chronic NGF treatment of cultured DRG neurons in rats induces a constitutively active cation conductance through TRPV1, which depolarizes the neurons and triggers spontaneous action potentials in the absence of any stimuli. Since NGF in the DRG is reported to increase after nerve injury, this NGF-mediated regulation of TRPV1 may be a cause of the pathogenesis of neuropathic pain.

Background Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. Methods Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox’s proportional hazards model was used to estimate hazard ratios (HR). Results During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40–59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40–49, 50–59, 60–69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8–0.9, P

Ten pairs of protrusions, called accessory lobes (ALs), exist at the lateral sides of the avian lumbosacral spinal cord. Histological evidence indicates that neuron-like cells gather in the ALs, and behavioral evidence suggests that the ALs act as a sensory organ of equilibrium during bipedal walking. Recently, using an electrophysiological method, we reported that cells showing Na+ currents and action potentials exist among cells that were dissociated from the ALs. However, it was unclear which isoforms of the voltage-gated sodium channel (VGSC) are expressed in the ALs and whether cells having neuronal morphology in the ALs express VGSCs. To elucidate these points, RT-PCR and immunohistochemical experiments were performed. In RT-PCR analysis, PCR products for Nav 1.1-1.7 were detected in the ALs. The signal intensities of the Nav 1.1 and 1.6 isoforms were stronger than those of the other isoforms. We confirmed that an antibody raised against an epitope peptide of the rat VGSC had cross-reactivity to chick tissues by Western blotting, and we performed immunofluorescence staining using the antibody. The AL contained cells having neuron-like morphology and VGSC-like immunoreactivity at their cytoplasm and/or cell membranes. Filament-like structures showing GFAP-like immunoreactivity infilled intercellular spaces. The VGSC- and GFAP-like immunoreactivities did not overlap. These results indicate that the neuronal isoforms of the VGSC are mainly expressed in the AL and that the neuron-like cells in the ALs express VGSCs. Our findings indicate that AL neurons generate action potentials and send sensory information to the motor systems on the contralateral side of the spinal segment.

Aims/Introduction Higher iron storage has been linked to an increased risk of type 2 diabetes, but little is known about the mediator of this association. Here, we prospectively investigated the association between circulating ferritin, a marker of iron storage, and the incidence of type 2 diabetes among Japanese individuals. Materials and Methods The participants were 4,754 employees who attended a comprehensive health check-up in 2008–2009 and donated blood for the study. During 5 years of follow up, diabetes was identified based on plasma glucose, glycated hemoglobin and self-report. Two controls matched to each case on sex, age and date of check-up were randomly chosen using density sampling, giving 327 cases and 641 controls with ferritin measurement. Cox proportional hazards regression was used to estimate the hazard ratio while adjusting for a series of potential confounders or mediators. Results Elevated serum ferritin levels were associated with a significantly increased risk of type 2 diabetes, with the hazard ratio adjusted for known risk factors in the highest vs lowest quartile of 1.42 (95% confidence interval: 1.03–1.96). This association was unchanged after adjustment for C-reactive protein and adiponectin, but attenuated after adjustment for liver enzyme and insulin resistance (hazard ratio 1.04). The ferritin–diabetes association was confined to non-obese participants. Conclusions These results suggest that elevated iron storage is associated with increased risk of type 2 diabetes in normal weight individuals, and that this association is partly mediated through liver dysfunction and resulting insulin resistance.

Introduction. The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. This study was designed to verify whether HbA1c or fasting plasma glucose (FPG) is more effective in detecting diabetic retinopathy in a Japanese population. Materials and Methods. The study subjects underwent health examinations between 2008 and 2009 with fasting. Of these participants, we analyzed the data for 2,921 Japanese men who had undergone an ophthalmologic examination. Retinopathy was classified into 7 categories according to a simplified diabetic retinopathy scale. The odds ratios of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results and Discussion. The odds ratios (95% CI) of retinopathy for HbA1c level categories, in ascending order, were 1.0 (ref.), 0.88 (0.28-2.75), 1.27 (0.44-3.69), 1.52 (0.48-4.79), 1.89 (0.52-6.85), 2.70 (0.66-11.10), 4.10 (0.80-21.00), and 6.34 (2.37-16.97) where the odds ratios significantly increased with HbA 1 c ≥ 6.8 % . The area under the curve (SE) for FPG and HbA1c was almost the same, at 0.668 (0.043) and 0.680 (0.043), respectively. Conclusions. It was clarified that the higher the level of HbA1c, the higher the prevalence of retinopathy, and there was no clear threshold. The detection ability of retinopathy was almost the same, suggesting that it is possible to detect the risk of retinopathy by HbA1c only.

Background The prevalence of overweight and obesity (OW/OB) has increased rapidly in Vietnam. This study aimed to elucidate the factors influencing OW/OB among secondary schoolchildren. Method A survey was conducted in January 2014 in four randomly selected state schools in two Hanoi urban districts, and 821 students in grade six (11–12 years old) participated. Definitions of OW/OB followed the World Health Organization standard cut-offs. Results Overall, 4.1% of children were underweight, 59.7% were normal weight, 17.1% were overweight, and 19.1% were obese. The odds of OW/OB were lowest among children whose parents had college/university degrees [father (aOR =0.65, 95% CI: 0.42–1.00); mother (aOR =0.63, 95% CI: 0.41–0.97)] compared with those whose parents had only a primary education. Children with an OW/OB family history had an increased risk of OW/OB. Other associated factors include parental OW/OB and birth weight (BW). The odds of OW/OB were highest among children with parents with OW/OB [father (aOR =2.022, 95% CI: 1.34–3.04); mother (aOR =2.83, 95% CI: 1.51–5.30)] compared with those with normal-weight parents. Children with both parents having OW/OB [both parents (aOR =6.59, 95% CI: 1.28–33.87) had the highest risk, followed by one parent (aOR =2.22, 95% CI: 1.50–3.27)] and then neither parent having OW/OB. Moreover, high-birth-weight children [BW ≥ 3500 g (aOR =1.52, 95% CI: 1.07–2.15)] had greater odds than did normal-birth-weight children. Children who slept 11 h per day [8–11 h (aOR =0.57, 95% CI: 0.40–0.81) or more (aOR =0.44, 95% CI: 0.22–0.87)] had lower OW/OB odds than those who slept 8 h or less. Children with specific positive lifestyle behaviours had lower risk of OW/OB than those who did not engage in positive lifestyle behaviours. The odds were lower among children who exercised for weight reduction (OR = 0.16, 95% CI: 0.11–0.23), lowered food intake (aOR = 0.12, 95% CI: 0.09–0.17), and added vegetables to their diet (aOR = 0.26, 95% CI: 0.19–0.35). Conclusion The results suggest that parents and children with OW/OB parents or a high BW should be educated to prevent OW/OB at an early stage. Positive lifestyle behaviours should be adopted by the students.

Background: Although glucose intolerance (GI) is diagnosed by fasting and 2h plasma glucose (PG) levels during a 75g OGTT, the upper limit of 1h PG level remains to be undefined in subjects with NGT. Previous report focusing on changes from NGT + IGT to diabetes has reported that 1h PG with ≥155 mg/dl is the risk for future diabetes in the world. However, IGT is well known as a risk factor for cardiovascular disease, few studies have focused on changes from NGT to GI. We therefore conducted a 5-year prospective study intended for NGT subjects to clarify the best predictor of the development of GI. Methods: To diagnose GI, we performed a 75gOGTT. We enrolled 1383 NGT subjects from The Toon Health Study. Finally, we analyzed 981 individuals with NGT who had a repeat health checkup. To investigate valuable predictive factors of progression of GI, we performed ROC curve analyses and compared fasting PG, 1h post OGTT, 2h post OGTT, and HbA1c. Results: ROC curve analyses revealed that 1h post OGTT was the best predictor of the development of GI in NGT (sensitivity 66%, specificity 74%, at a cutoff value of 149 mg/dl). In NGT with 1h PG>149mg/dl, odd ratio for the development of GI was 4.7 (95% CI: 3.25-6.80) compared to the reference after adjustment for age, sex, and BMI (p Conclusions: PG level at 1h post 75g OGTT was the best predictor of the development of GI in NGT. Disclosure M. Takakado: None. Y. Takata: None. T. Hadate: None. Y. Matsushita: None. R. Kawamura: None. K. Maruyama: None. I. Saito: None. H. Osawa: None.

Increasing evidence has suggested a protective role of vitamin D on diabetes, but epidemiologic evidence is scarce among Asian populations. Here we prospectively examined the association between serum 25-hydroxyvitamin DA nested case-control study was conducted in a biomarker cohort of 4754 employees (baseline age 34-69 years) who had attended in a comprehensive health checkup and donated a blood sample. Diabetes diagnosis was based on plasma glucose, glycated hemoglobin, and self-reporting during the 5-year follow-up. Using density sampling, two controls were randomly matched to each case by sex, age, and date of checkup; 336 cases and 668 controls had serum 25(OH)DSerum 25(OH)DHigher circulating 25(OH)D

In humans, resistin is predominantly expressed in monocytes and macrophages, and involved in insulin resistance, atherosclerosis, and cardiovascular diseases. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at -420 (rs1862513) in the human resistin gene increased susceptibility to type 2 diabetes. Genetically, serum resistin was positively associated with the number of the G-allele at SNP-420 in the general Japanese population. Epigenetically, serum resistin was inversely associated with methylation of the C-allele at SNP-420. However, interaction between SNP-420 and environmental factors remains to be elucidated. The aim of this study was to investigate the association between serum resistin and physical activity, and the effect of SNP-420 on this association. The Toon Genome Study is a cohort study of Japanese community-dwelling subjects. A total of 1981 participants were cross-sectionally analyzed. Serum resistin was measured by ELISA. Physical activity was measured for 7 days using a waist-worn accelerometer (Lifecorder, Suzuken Co). Physical activity was also assessed using a questionnaire (the Japan Arteriosclerosis Longitudinal Study Physical Activity Questionnaire, JALSPAQ). Serum resistin was inversely associated with the quartile of moderate-intensity (3Mets or more) physical activity time (Q1 12.8, Q2 12.2, Q3 12.3, Q4 11.6 ng/ml; P for trend = 0.005; after adjustment for age, gender, and BMI). This inverse association was strongest in the C/C genotype of SNP-420. HOMA-IR was positively associated with serum resistin, and inversely associated with moderate-intensity physical activity time in the C/C genotype (Q1 1.51, Q2 1.52, Q3 1.36, Q4 1.32; P for trend = 0.01; after adjustment for age, gender, and BMI). Therefore, serum resistin and insulin resistance were inversely associated with physical activity in the C/C genotype of SNP-420 in the general Japanese population. Disclosure R. Kawamura: None. Y. Tabara: None. Y. Takata: None. M. Takakado: None. Y. Matsushita: None. T. Hadate: None. H. Onuma: None. K. Maruyama: None. T. Tanigawa: None. I. Saito: None. H. Osawa: None.

Background: The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort. Methods: Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (

Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.

Background Diabetes Mellitus (DM) has rapidly become a major public health concern in Vietnam. Although the prevalence of DM has been studied in northern and southern Vietnam, little data are available for the central region. Therefore, the aims of this survey were to estimate the prevalence of DM and to identify the perception of and factors associated with DM among the adult population in central Vietnam. Methods We conducted a cross-sectional, population-based survey in Khánh Hòa Province, Vietnam in December 2014 using three-stage cluster sampling and probability proportional to size sampling in line with the World Health Organization STEPwise approach. Four hundred and eighty residents aged 20–70 years were selected from 30 villages in 10 wards/communes. After obtaining informed consent, all residents participated in interviews regarding lifestyle, medical history, and perception of DM and underwent physical measurements and blood examination for fasting blood glucose and glycated hemoglobin. Factors associated with DM were analyzed using a logistic regression model. Results A total of 376 residents were enrolled (response rate: 78.3%; females: 59%; rural residents: 61%). Among the participants, 14.3% and 18.9% of males and females, respectively, were classified as overweight/obese according to body mass index (BMI), 37.7% and 22.1%, respectively, had hypertension, and 36.4% and 11.7% had metabolic syndrome. The prevalence of DM in the entire population was 7.2% (27/376; 95% confidence interval [CI]: 4.6–9.8). Participants aged 60–70 years were more likely to have DM than those aged 30–39 years (adjusted odds ratio [aOR]: 8.7; 95%CI: 1.4–56.0), and participants classified as obese were more likely to have DM than those with normal or low BMI (aOR: 10.2; 95%CI: 2.2–50.2). Furthermore, more than two-thirds (254/376, 67.6%) of the participants either did not understand or had never heard of DM, and less than half of the DM cases (12/27, 44%) were aware of their history of DM. Conclusions The results of this study suggested that the prevalence of DM among the adult population in central Vietnam was slightly higher than that in other areas. Additional research is needed to further explore perceptions of and practices regarding DM.

ObjectiveParoxysmal atrial fibrillation could progress to permanent atrial fibrillation. Whether the transmitral inflow waves could be used to predict progression from paroxysmal atrial fibrillation to permanent atrial fibrillation is unknown. Therefore, we investigated the association between the transmitral inflow waves and progression of paroxysmal atrial fibrillation.MethodWe performed a retrospective study by analysing clinical and echocardiographic data from 88 patients with paroxysmal atrial fibrillation. We excluded patients who had structural heart disease, significant valvular disease, cardiomyopathy, cardiac device implantation or a left ventricular ejection fraction ResultThe patients with progression to permanent atrial fibrillation were more likely to be male and had lower peak A velocity than those without progression. After adjusting for covariates, lower peak A velocity remained the independent predictor of progression to permanent atrial fibrillation (p=0.025).ConclusionThe A velocity could be useful for predicting progression to permanent atrial fibrillation in Asian people.

Aims/Introduction The objective of the present study was to clarify the validity of β‐cell function‐related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients. Materials and Methods In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross‐sectional study examining the relationship between the homeostasis model assessment of β‐cell function (HOMA‐β) and C‐peptide‐based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several β ‐cell function‐related indices using a receiver operating characteristic (ROC) curve analysis. Results The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA‐β, followed by the fasting serum C‐peptide immunoreactivity index (CPI); the fasting serum C‐peptide immunoreactivity itself (F‐CPR) had the least correlation. The CPI, HOMA‐β and SUIT were significantly lower in the insulin‐requiring group than in the non‐insulin‐requiring group, even after adjustments for confounding factors (P

Objective: To examine the combined effect of CT-measured visceral fat area (VFA) and adiponectin level against the clustering of metabolic risk factors. Design and Methods: The subjects were 6,996 Japanese. The subjects were divided according to the combinations of VFA and adiponectin level quartiles and the odds ratio for multiple risk factors of metabolic syndrome were calculated (adjusted for age and lifestyle factors using logistic regression analyses). Group with the lowest VFA and the highest adiponectin level was used as a reference. The correlation between adiponectin level and each metabolic risk factor was evaluated. Results: The strongest correlation was observed between adiponectin level and high-density lipoprotein cholesterol levels (r = 0.369 and 0.439 for men and women). Both VFA and adiponectin level were independently associated with the clustering of metabolic risk factors (interaction P = 0.58 and 0.11 for men and women). The odds ratio for the clustering of metabolic risk factors in the group with the highest VFA and the lowest adiponectin level, compared with the group with the lowest VFA and the highest adiponectin level, was 12.7 (9.7-16.6) for men and 13.5 (6.0-30.2) for women. Conclusion: The ability to detect metabolic syndrome could be improved by examining adiponectin level in conjunction with VFA.

Objective To examine the incidences of metabolic risk factors according to changes in visceral fat area (VFA) in a large Japanese population. Design and Methods The subjects were 973 men who received a computed tomography (CT) examination in health checkups twice (2004-2005 and 2007-2008), and not having two or more of metabolic risk factors (except for the waist circumference) in 2004-2005. VFA was measured using CT. To assess the potential influence of changes in VFA for the 3-year incidences of each metabolic risk factor and clustering metabolic risk factors, logistic regression analyses were used. Results A significant association was observed between the change in VFA and the components of the metabolic risk factors. Incidences of the components of the metabolic risk factors were significantly higher among subjects with a larger increase in VFA and were significantly lower among subjects with a larger decrease in VFA (trend P < 0.001). Significant increases in the odds ratios for the incidences of high triglycerides and low high-density lipoprotein cholesterol level were observed among subjects with ≥50 cm2 VFA increase. Conclusions The adoption of a lifestyle that does not increase the VFA is important for preventing metabolic syndrome.

The relationship between different types of meat intake and the risk of type 2 diabetes remains unclear. We prospectively examined the association between total meat, total red meat, unprocessed red meat, processed meat and poultry intake and the incidence of type 2 diabetes. Subjects were 27 425 men and 36 424 women aged 45–75 years who participated in the second survey of the Japan Public Health Center-based Prospective Study, and had no history of type 2 diabetes, cancer, stroke, IHD, chronic liver disease or kidney disease. Meat intake was estimated using a validated 147-item FFQ. OR of self-reported, physician-diagnosed type 2 diabetes over 5 years were estimated using a multiple logistic regression. A total of 1178 newly diagnosed cases of type 2 diabetes were self-reported. Intakes of total meat and total red meat were associated with the increased risk of type 2 diabetes in men but not in women. The multivariate-adjusted OR for the highest quartile compared with the lowest quartile of total meat and total red meat intake were 1·36 (95 % CI 1·07, 1·73; P for trend = 0·006) and 1·48 (95 % CI 1·15, 1·90; P for trend = 0·003) for men, respectively, and 0·82 (95 % CI 0·62, 1·09; P for trend = 0·14) and 0·77 (95 % CI 0·57, 1·02; P for trend = 0·08) for women, respectively. Intakes of processed red meat and poultry were not associated with the increased risk of diabetes in either men or women. In conclusion, elevated intake of red meat is associated with the increased risk of type 2 diabetes in Japanese men but not in women.

Background: The association between the circulating fatty acid (FA) composition and type 2 diabetes (T2D) has been reported in Western populations, but evidence is scarce among Asian populations, including Japanese, who consume large amounts of fish.Objective: The objective of the present study was to prospectively examine the association between circulating concentrations of individual FAs and T2D incidence among Japanese adults.Methods: We conducted a nested case-control study in a cohort of 4754 employees, aged 34-69 y, who attended a comprehensive health checkup in 2008-2009 and donated blood samples for the Hitachi Health Study. During 5 y of follow-up, diabetes was identified on the basis of plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case by sex, age, and date of checkup were randomly chosen by using density sampling, resulting in 336 cases and 678 controls with FA measurements. GC was used to measure the FA composition in serum phospholipids. Cox proportional hazards regression was used to estimate the HRs and 95% CIs after adjusting for potential confounders. We examined the association of T2D risk with 25 different individual and combinations of FAs.Results: T2D risk was positively associated with serum dihomo-γ-linoleic acid concentration (highest compared with the lowest quartile-HR: 1.49; 95% CI: 1.04, 2.11; P-trend = 0.02) and inversely associated with Δ5-desaturase activity (highest compared with the lowest quartile-HR: 0.72; 95% CI: 0.52, 0.99; P-trend = 0.02), independent of body mass index (BMI). There were also inverse associations between T2D risk with serum total n-6 (ω-6) polyunsaturated fatty acids (PUFAs), linoleic acid, and cis-vaccenic acid, but these were attenuated and became nonsignificant after adjustment for BMI. Serum n-3 (ω-3) PUFAs and saturated fatty acids (SFAs) were not associated with T2D risk.Conclusions: T2D risk was associated with circulating concentrations of the n-6 PUFA dihomo-γ-linoleic acid and Δ5-desaturase activity but not with n-3 PUFA or SFA concentrations in Japanese adults.

We sought to explore the relationship between depressive symptoms and urinary 8-hydroxydeoxyguanine (8-OHdG), a biomarker of systemic oxidative DNA damage and repair, among 301 men and 210 women aged 21–67 years working in two municipal offices. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale (CES-D). The geometric mean and its 95% confidence interval (CI) of urinary 8-OHdG concentrations were calculated according to the quartile of CES-D score. The prevalence of depressive symptoms, defined as having CES_D of ≥16, was 35.9% in men and 35.2% in women. There was no significant difference in geometric mean of urinary 8-OHdG concentrations according to the levels of depressive symptoms. In men, the multivariable-adjusted geometric mean of urinary 8-OHdG concentrations (95% CIs) in the first, second, third, and fourth category of depressive symptoms was 1.09 (1.02–1.16), 1.16 (1.08–1.24), 1.15 (1.07–1.24), and 1.10 (1.02–1.18), respectively ( p for trend=0.86). Similarly, no significant association was found in the analyses among women, nonsmoking men, and smoking men. The lack of association between depressive symptoms and urinary 8-OHdG concentrations may indicate the absence or more complex interactions between milder forms of depression and systemic oxidative DNA damage and repair in well-functioning population.

Objective It remains unsettled whether dietary patterns play a role in insulin resistance. We assessed the association of major dietary patterns with C-peptide concentrations in a Japanese working population. Methods A cross-sectional study was conducted in 456 municipal employees (270 men and 186 women) 21 to 67 y old who participated in a health survey at the time of their periodic checkup. The dietary patterns were derived by using the principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief dietary history questionnaire. Multiple regression analysis was used to estimate the means of C-peptide concentrations across tertiles of each dietary pattern score with the adjustment of potential confounders, including age, body mass index, physical activity, smoking, alcohol drinking, and energy intake. Results We identified three dietary patterns: healthy, animal food, and Westernized breakfast patterns. The Westernized breakfast pattern was characterized by high intakes of bread, confectionaries, and milk and yogurt but low intakes of rice and alcohol and was inversely associated with C-peptide concentrations in women but not in men. The multivariable-adjusted means of C-peptide concentrations were 1.03 ng/mL (95% confidence interval 0.95–1.12), 0.95 ng/mL (95% confidence interval 0.88–1.03), and 0.89 ng/mL (95% confidence interval 0.82–0.97) for the lowest through the highest tertiles of the Westernized breakfast pattern score (P for trend = 0.015) in women. Other dietary patterns were not appreciably associated with C-peptide concentrations. In a subgroup, similar associations were observed between dietary patterns and the homeostasis model assessment of insulin resistance. Conclusion The Westernized breakfast pattern may be associated with a lower insulin resistance in Japanese women.

OBJECTIVE The effects of longitudinal changes in the visceral fat area (VFA), and other anthropometric indices, on the risk factors of metabolic syndrome were not studied. We calculated the changes in metabolic risk factors in relation to changes in certain anthropometric indices in a large-scale study of Japanese men. RESEARCH DESIGN AND METHODS The subjects were 1,106 men participating in the Hitachi Health Study who received a computed tomography examination in both 2004 and 2007. VFA, subcutaneous fat area (SFA), and waist circumference were measured using the computed tomography. We examined how longitudinal changes in each anthropometric index over a 3-year period influenced the value of each metabolic risk factor. RESULTS Changes (∆) over a 3-year period in body weight, SFA, and waist circumference strongly correlated, while the changes in body weight and VFA were weakly correlated. Changes in the VFA were associated with changes in metabolic risk factors, especially changes in triglyceride and HDL; we found these changes to be independent of the ∆body weight and ∆waist circumference. CONCLUSIONS Change in body weight is not a precise surrogate marker of ∆VFA, and repeated VFA measurements over time are useful. Adopting a lifestyle that does not increase the VFA is important in preventing metabolic syndrome.

Background Living alone has been suggested as a risk factor for suicide. However, the effect on suicide risk of living together with spouse, child(ren) and parent(s) is unclear. This study aims to examine the association between living arrangements with spouse, child(ren), and parent(s) and suicide in a Japanese men and women. Methods Altogether 104, 528 participants aged 40–69 years, who completed baseline questionnaire (1990–1994), were followed for death through December 2005. We used Cox proportional hazards regression model to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for suicide according to living arrangements. Results During an average 13.2-year follow up, 406 suicidal deaths were recorded. Men living without a spouse and women living with a parent(s) only were at increased risk of suicide than those living with a spouse only. The multivariate HR (95% CI) in men were as follows: “living with a parent(s) only”, 1.86 (1.03–3.36); “living with a child(ren) only”, 2.20 (1.32–3.66); “living with a parent(s) and child(ren)”, 1.95 (1.02–3.72); and “living alone”, 1.80 (0.99–3.25); and in women was as follow “living with a parent(s) only”, 3.80 (1.90–7.61). Suicide risk was significantly decreased among women living with a spouse and child(ren) as compared with women living with a spouse only (HR 0.58, 95%CI 0.34 to 0.98). Conclusions Men living without a spouse and women living with a parent(s) only were at increased risk of suicide. Women living together with a spouse and child(ren) were at decreased risk of suicide.

Weight gain after smoking cessation may deteriorate metabolic risk profiles, including that for metabolic syndrome. How risk profiles change according to the duration of smoking cessation and whether the visceral fat area (VFA) or the subcutaneous fat area (SFA) contributes to these changes remains uncertain. The subjects comprised 5,697 Japanese men who underwent an abdominal computed-tomography examination during a health check-up. Using never smokers as a reference group, the odds ratios of having metabolic syndrome and its components, defined using the National Cholesterol Education Program Adult Treatment Panel IIIcriteria, were calculated for each smoking category with adjustments for age, alcohol drinking, and physical activity (model 1) using a logistic regression analysis. Additional adjustments were also made for either VFA (model 2) or SFA (model 3). Current smokers had the lowest VFA (120.4 cm²) whereas ex-smokers (124.0-132.0 cm²) had a higher VFA than nonsmokers (123.1 cm²). Among the ex-smokers, VFA tended to decrease with increasing years of smoking cessation. In model 1, the odds ratios of having metabolic syndrome for current smokers and ex-smokers with smoking cessation for ≤ 4, 5-9, 10-14, and ≥ 15 years were 1.02, 1.33, 1.36, 1.40, and 1.09, respectively. The elevated odds ratios among ex-smokers (≤ 14 years) were reduced by 35-55.6% after further adjustment for VFA but not for SFA. Smoking cessation is associated with a deterioration of the metabolic risk profile, which can be ascribed, at least in part, to an increase in VFA not SFA.

Background Few studies have examined the impact of weight change in different periods of lifetime on type 2 diabetes risk, and the association of weight loss with type 2 diabetes is unclear. We prospectively investigated the association of weight change since age 20 y and that during middle-to-late adulthood with the incidence of type 2 diabetes. Methods Subjects were 52 014 men and women aged 45–75 y who participated in the Japan Public Health Center-Based Prospective Study and had no history of diabetes. ORs of self-reported physician-diagnosed type 2 diabetes for weight change between age 20 y and baseline survey (mean age 50.6 y) and during 5 y between baseline and second surveys were estimated using logistic regression analysis. Results During the 5-year period following 5-year survey, 989 newly diagnosed cases of type 2 diabetes were self-reported. Weight gain from age 20 y was associated with an increased risk of type 2 diabetes. The multivariate-adjusted OR (95% CI) for a weight gain of ≥5 kg versus a stable weight were 2.61 (2.11 to 3.23) in men and 2.56 (1.95 to 3.35) in women. A weight gain of ≥5 kg over the 5-y following the baseline survey was also associated with an increased risk in women. No association with weight loss was observed for either period. Conclusions These results suggest that long-term weight gain from early adulthood to middle-age increases risk of type 2 diabetes in men and women and that risk is further enhanced by weight gain in later life in women.

Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. Subjects were 521 municipal employees (309 men and 212 women), aged 21–67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D ⩾16) with adjustment for potential confounding variables. We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62–1.59) and 0.44 (0.25–0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.

Folate and homocysteine have been implicated to have a role in depression. However, results of epidemiologic studies on this issue have been inconsistent. The objective of this study was to clarify the association between serum folate and homocysteine concentrations and depressive symptoms in Japanese adults. We analyzed cross-sectional data for 530 municipal employees (313 men and 217 women), aged 21–67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D scale scores of ⩾16) with adjustment for potential confounding variables. In total, 113 men (36.1%) and 79 women (36.4%) had depressive symptoms. A higher serum folate was associated with a decreased prevalence of depressive symptoms in men. The multivariate-adjusted odds ratios (95% confidence interval) of depressive symptoms for the lowest to highest quartiles of serum folate were 1.00 (reference), 0.53 (0.27–1.03), 0.33 (0.16–0.68) and 0.51 (0.25–1.03), respectively (trend P=0.03). Furthermore, the data suggested a positive association between serum homocysteine and depressive symptoms in men (trend P=0.06). In women, neither folate nor homocysteine was associated with depressive symptoms. Low serum folate may be related to an increased prevalence of depressive symptoms in Japanese men.

OBJECTIVE Although abdominal obesity and related metabolic abnormalities are hypothesized to promote colorectal carcinogenesis, direct confirmation of this effect is required. Here, we examined the relation of early-stage colorectal neoplasia to visceral fat area and markers of insulin resistance. RESEARCH DESIGN AND METHODS Subjects were participants in a comprehensive health screening conducted at the Hitachi Health Care Center, Ibaraki, Japan. During a 3-year period (2004–2007), a total of 108 patients with early-stage colorectal neoplasia, including 22 with early cancer, were identified among individuals who received both colorectal cancer screening and abdominal computed tomography scanning. Three control subjects matched to each case subject were randomly selected from those whose screening results were negative. Conditional logistic regression analysis was used to examine the association of measures of obesity and markers of insulin resistance with colorectal neoplasia, with adjustment for smoking and alcohol drinking. RESULTS Visceral fat area, but not subcutaneous fat area, was significantly positively associated with colorectal cancer, with odds ratios (95% CI) for the lowest to highest tertile of visceral fat area of 1 (reference), 2.17 (0.45–10.46), and 5.92 (1.22–28.65), respectively (Ptrend = 0.02). Markers of insulin resistance, particularly fasting glucose, were also positively associated with colorectal cancer risk. In contrast, no associations were observed for colorectal adenomas. CONCLUSIONS These results suggest that visceral adipose tissue accumulation and insulin resistance may promote the development of early-stage cancer but not adenoma in the colorectum.

Investigations suggest a protective role of n-3 polyunsaturated fatty acids (PUFA) but opposing roles of n-6 PUFA in inflammation, but the effects in vivo the human are not clear. We therefore tested the hypothesis that higher intakes of n-3 PUFA and n-6 PUFA are associated with lower levels of inflammation among a population consuming a diet high in PUFA. This study aimed to assess the association between PUFA intake and serum C-reactive protein (CRP) concentrations in a group of Japanese employees. The study subjects were 300 men and 211 women aged 21 to 67 years working in 2 municipal offices of Japan. We measured the serum high-sensitivity CRP concentrations by the latex agglutination nephelometry method and assessed dietary habits by a validated self-administered diet history questionnaire. We analyzed the data using multiple linear regression analysis with adjustment for potential confounding variables. Mean serum CRP concentrations tended to decrease as the intake of eicosapentaenoic acid, docosahexaenoic acid, or their combination increased in men and women, although none of these relationships was statistically significant. In men, there were statistically significant inverse relationships between dietary intake of n-3 or n-6 PUFA and serum CRP concentrations (P for trend = .03 and .008, respectively). Among specific PUFA, only alpha-linolenic acid and linoleic acid showed clear inverse relationships (P for trend = .001 and .003, respectively) in men. The results suggest that increased intake of not only alpha-linolenic acid (n-3 PUFA) but also linoleic acid (n-6 PUFA) has a beneficial effect on systemic inflammation in men.

OBJECTIVE:To investigate visceral fat accumulation and markers of insulin resistance in relation to elevated depressive symptoms (EDS). METHODS:Participants were 4,333 male employees (mean age, 49.3 years) who underwent abdominal computed tomography scanning, measured fasting insulin, and did not self-report diabetes and mental disorders under treatment and history of cancer, myocardial infarction, and stroke. Multivariable logistic regression was used to assess the association of EDS with abdominal fat deposition and markers of insulin resistance. RESULTS:Visceral fat area (VFA) and fasting insulin were significantly, positively associated with EDS. Multivariable-adjusted odds ratios (95% confidence interval) of high VFA for the lowest through highest quartile of depression score were 1 (reference), 1.18 (0.97-1.42), 1.25 (1.02-1.54), 1.23 (1.01-1.51), respectively, and corresponding figures for high fasting insulin were 1 (reference), 0.98 (0.80-1.19), 1.12 (0.91-1.38), and 1.29 (1.06-1.57), respectively. Subcutaneous fat area was not associated with EDS. CONCLUSIONS:Results suggest that EDS is related to visceral, but not subcutaneous, fat accumulation and insulin resistance in middle-aged Japanese men.

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Background: Elevated mean corpuscular volume (MCV) is a traditional biological marker for alcohol abuse and alcoholism, but the underlying mechanism is unclear. Three recent epidemiologic studies consistently showed that MCV was elevated by alcohol drinking more markedly among individuals with genetically inactive aldehyde dehydrogenase-2 (ALDH2) (encoded by ALDH2*2 mutant allele) than those with active ALDH2 (encoded by ALDH2*1/2*1 genotype), suggesting that the elevated MCV was etiologically linked to acetaldehyde exposure. The purpose of the present study was to clarify further this relationship by examining the status of folate and vitamin B12. Methods: The study participants were 159 men who were aged 40 to 69 years and randomly selected from a Japanese rural population. The genetic polymorphism of ALDH2 was determined by PCR–restriction fragment length polymorphism method; data on alcohol drinking and other lifestyles were collected using a structured questionnaire; serum concentrations of folate and vitamin B12 were measured using the protein competitive reaction method, and blood cell counts were measured by routine methods. A multiple linear regression model was used to analyze the data. Results: The relationship between alcohol drinking and serum folate concentration was significantly different between ALDH2 genotypes, indicating that the reduction of serum folate by alcohol drinking was more marked in men with ALDH2*1/2*2 than those with ALDH2*1/2*1. The relationship between alcohol drinking and elevated MCV was significantly stronger in men with ALDH2*1/2*2 than those with ALDH2*1/2*1 even after adjustment for serum folate and vitamin B12 concentrations. Conclusions: These findings indicate that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated MCV by alcohol drinking.

To investigate the association between an individual's ability to recognize his/her energy intake and energy expenditure with the status of diabetes mellitus (DM) control, we conducted a cross-sectional study using data from 62 outpatients with type 2 DM (46 men and 16 women), aged 33–77 years, from two hospitals in Tokyo in 1999. A dietitian–interviewer asked the patients to estimate their probable energy intake and expenditure in recent days (self-estimated energy intake and expenditure, respectively). Subsequently, a dietary survey was conducted to estimate the patient's energy intake by a self-recorded method with a dietitian's interview for three continuous business days; the physical exercise levels were measured using a pedometer with multiple-memory accelerometers for one week. The percentage of subjects whose self-estimated energy intake was within ±10% of the dietary survey-based energy intake became significantly lower as the control status worsened (35.6, 12.9, and 11.1% in the first, second, and third tertile groups of HbA 1c , respectively; P = 0.015). Similar but non-significant results were observed for the energy expenditure ( P = 0.35). Since the control status of DM was worse among patients who could not recognize their amount of caloric intake and expenditure, a training program to improve such recognition ability may be needed.

Dietary therapy is extremely important for renal failure patients, and the diet for these patients should be based on low-protein and high-energy foods. Low-protein and high-energy rice and noodles as staple foods have already been developed and utilized for dietary therapy, although low-protein and high-energy bread is not presently available. We made low-protein and high-energy loaf samples exclusively for kidney disease patients by using starch flour that is designated as a food for special dietary use. We compared this exclusive bread to ordinary bread made of hard flour, and performed organoleptic tests (n=56), textural measurements and color recognition tests.The exclusive loaf samples made from starch flour gave high-preference scores in the organoleptic tests. In comparison to wheat bread, the nutritive values of the sample loaves were lower in protein (-32%, -45%) higher in energy (+37%, +40%), lower in phosphorus (-16%, -20%), lower in potassium (-16%, -20%) and lower in sodium (-67%, -66%). We conclude from these results that this exclusive bread made from starch flour is potentially useful as a staple food in dietary therapy for renal failure patients who require special foods.

Background The present study examined the prevalence of diabetes in Japan during the late 1990s and early 2000s using the Japan Public Health Center-based Prospective Diabetes cohort. We also investigated the distributions of HbA1c values in noncompliant diabetic participants in the cohort. Methods A total of 28 183 registered inhabitants aged 46-75 years from 10 public health center areas were included in the initial survey. The 5-year follow-up survey included 20 129 participants. The prevalence of diabetes was estimated using both a self-reported questionnaire and laboratory measurements. Among the participants who reported the presence of diabetes on the questionnaire (self-reported diabetes), the distributions of HbA1c values were described according to their treatment status. Results The age-standardized prevalence of diabetes in 55- to 74-year-old adults was 8.2% at the initial survey and 10.6% at the 5-year follow-up. At the initial survey, among participants with self-reported diabetes, the mean HbA1c values in the participants who had never and who had previously received diabetes treatment were 7.01% (standard deviation [SD] 1.56%) and 6.56% (SD 1.46%), respectively. Approximately 15% of the participants who had self-reported diabetes but had never received diabetes treatment had an HbA1c ≥ 8.4%. Conclusions The prevalence of diabetes increased in the JPHC cohort between the late 1990s and early 2000s. A certain proportion of participants who were aware of their diabetes but were not currently receiving treatment had poor diabetic control. Efforts to promote continuous medical attendance for diabetes care may be necessary.