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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

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.

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: 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 (

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.

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.