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Purpose:To evaluate the effect of a mobile digital intervention on voiding patterns, we performed 24-h voided volume monitoring in individuals with metabolic disorders.\nMethods:Participants with metabolic disorders were grouped into either the intervention group (n = 17), who had access to a smartphone app (CARADA), or the non-intervention group (n = 11), who did not. Urine monitoring was conducted for 24 h using a novel digital self-health monitoring system for urine excretion (s-HMSU). Body weight, abdominal circumference, blood pressure, and biomarkers were measured.\nResults:Physical findings and blood test results at baseline and 6 months indicated no significant between-group differences. Night-time frequency did not change between baseline and 6 months in the intervention group but significantly worsened at 6 months in the non-intervention group, as compared to baseline (1.0 ± 0.7 vs. 1.5 ± 0.5, p, 論文

Background We developed and compared two liquid chromatography methods, one with UV/Visible spectrophotometric detection (HPLC) and the other with mass spectrometric detection (LC-MS), for quantifying very-long chain fatty acids (VLCFA) in human plasma. Association of VLCFA with various cardiovascular risk factors were evaluated. Method Fasting blood samples were collected from 541 human volunteers (242 men and 299 women; mean age ±SD, 58.9 ± 12.4 years), including 429 and 112 individuals with and without hypertriglyceridemia, respectively. Esterified VLCFA were saponified and derivatized with 2-nitrophenylhydrazine. Separation of VLCFA species was achieved with C4 Mightysil column (HPLC) and Ascentis Express Phenyl-Hexyl column (LC-MS) followed by spectrophotometric and selected-reaction monitoring mode of mass spectrometric detection, respectively. Results The HPLC assay of VLCFA was precise with intra-assay imprecision of 2.5% to 6.9% and inter-assay imprecision of 3.2% to 9.5%. Moreover, there was an excellent correlation (r > 0.96) between HPLC and LC-MS methods. The 95 percentile reference intervals (RI; upper limit) of VLCFA were determined to be 41.3 µmol/L in healthy volunteers. Plasma VLCFA were significantly correlated with triglycerides (Spearman’s ρ = 0.306, P < 0.001) and total cholesterol (Spearman’s ρ = 0.251, P < 0.001). All species of VLCFA were significantly elevated in hypertriglyceridaemic individuals compared with control. Conclusion We established LC-based assays of VLCFA with either spectrophotometry or mass spectrometry as a detection system. Hypertriglyceridaemia is significantly associated with elevated concentration of each species of VLCFA.

Numerous studies have revealed distinct differences in the profiles of gut microbiota between non-obese (NO) and obese (OB) individuals. To date, however, little is known if any disparities in the community of gut microbiota exist between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) subjects. We therefore aimed to comprehensively characterize the gut microbiota and circulating metabolites in serum from both MHO and MUO residing in the remote island, Kumejima, where the prevalence of obesity is one of the highest in Japan, and explored possible correlations between the gut microbiota profile and markers of metabolic syndrome. In our data, MUO showed significantly higher levels of g_Paraprevotella, g_Cloacibacillus, g_Atopobium and g_Megasphaera in comparison to MHO. MUO also showed significantly lower levels of g_Holdemania, f_Ruminococcaceae;g_Ruminococcus, g_Eggerthella, g_Phascolarctobacterium and f_[Mogibacteraceae];g_ as compared to MHO, with a number of these genera negatively correlating with value of circulating triglyceride, total-cholesterol and LDL-cholesterol. In contrast to MHO, MUO showed an imbalance of serum metabolites, with a significant elevation in 2-oxoisovaleric acid, pyruvic acid, 2-hydroxybutyric acid, and creatine. Our data highlight unmet needs in precision approaches for the treatment of obesity, targeting the gut microbiota profile and serum metabolites in a distinct population affected by obesity.

Purpose Childhood obesity is rapidly increasing world-wide and is largely the consequence of adoption of unhealthy diets excessive in calories and salt (NaCl) as well as devoid in pivotal micronutrients such as potassium (K) and magnesium (Mg). Education-based programs aiming to encourage healthy food knowledge and behaviors are crucial at a young age, and for this purpose, convenient ways to assess daily dietary intake are warranted. We therefore attempted to evaluate the dietary intake of Okinawan school children in Japan by analyzing a series of biomarkers in morning spot urine samples and explore whether these biomarkers correlate with body weight and a series of metabolic parameters. Methods We enrolled 98 third-grade elementary school children in Okinawa, Japan. Morning spot urine samples were collected and analysed using high performance liquid chromatography (HPLC) to assess dietary intake. Results We found that estimated daily NaCl intake was higher in obese/overweight children as compared to healthy-weight children (p = 0.0001). There was also a significant positive correlation between body mass index (BMI) and NaCl intake (Spearman) (ρ = 0.45, p p = 0.01). Furthermore, Na/K ratio was higher in samples collected on Monday (weekend) as compared to samples collected on Thursday or Friday (weekday) (p

The easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients.The derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF.Predicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p 0.001; stage II vs. stage III, p 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts.Our modification of the original GAP model showed improved performance in East-Asian IPF patient populations.

This cohort study aimed to investigate the association between household income and incident hypertension in a Japanese employed population. During 2012, a total of 4314 normotensive daytime employees (3153 men and 1161 women) were included in this study. Participants had a wide range of occupations and were employed at one of 12 workplaces from various economic sectors in Japan. After a 2-year follow-up, incident hypertension was compared among groups according to household income

Serum high‐molecular‐weight adiponectin (HMWA) has a positive correlation with insulin secretion in the Japanese population. To validate this correlation, we investigated the correlation between serum HMWA and proinsulin, a marker of β‐cell dysfunction, in this population. A total of 488 participants (53.9% women) aged 35–79 years not taking oral hypoglycemic agents and/or insulin were enrolled. HMWA was significantly and inversely correlated with proinsulin adjusted for age and sex (partial regression coefficient β = −0.37; 95% confidence interval −0.46 to −0.28). When the participants were divided into two groups by median values of body mass index (23.2 kg/m2), serum insulin (4.3 µU/mL) or homeostasis model assessment of insulin resistance (1.0), similar inverse correlations were observed adjusted for age and sex in both groups. Our results showed that the HMWA level was inversely correlated with the proinsulin level in a general Japanese population., The high‐molecular‐weight adiponectin level was inversely correlated with the proinsulin level in a general Japanese population.

Aims/Introduction We explored the association between fatty liver and pancreatic β‐cell dysfunction in a general population. Materials and Methods This cross‐sectional study included 489 (53.8% women) community‐dwelling Japanese adults. The extent of fatty liver was estimated using the fatty liver index (FLI). After all participants were divided into three groups – low (FLI, The degree of fatty liver was positively associated with proinsulin level. This association was observed regardless of obesity or hyperinsulinemia. The degree of fatty liver might reflect β‐cell dysfunction.

Aims/Introduction We investigated associations between glucose tolerance and β‐cell function using a series of estimation methods in a population‐based study. Materials and Methods Data from the Dynamics of Lifestyle and Neighborhood Community on Health Study were analyzed. A total of 489 participants (263 women) were divided into three groups: normal glucose tolerance (NGT), prediabetes (PDM) and diabetes group. We estimated β‐cell function by the homeostasis model assessment of β‐cell function, proinsulin level (PI), C‐peptide index, proinsulin‐to‐C‐peptide ratio (PI/CPR) and proinsulin‐to‐insulin ratio. Because data on all five parameters of β‐cell function showed skewed distributions, the values of these parameters were normalized by natural logarithmic (ln) transformation. Next, the association between glucose tolerance and β‐cell function among participants without diabetes was examined. In this analysis, glucose tolerance was assessed based on glycated hemoglobin levels. Results In the crude analysis, ln(PI) and ln(PI/CPR) were significantly higher in the diabetes group than those in the PDM and NGT groups, and these parameters were significantly higher in the PDM group than in the NGT group. Only ln(PI) in the PDM group was significantly higher compared with that in the NGT group after adjustment for age, sex and body mass index (ln[PI]: PDM group 2.38 pmol/L, 95% confidence interval 2.29–2.47 pmol/L; NGT group 2.17 pmol/L, 95% confidence interval 2.12–2.22 pmol/L; P, Proinsulin is the most sensitive to reflect glucose intolerance.

Childhood obesity is rapidly increasing worldwide and is largely the consequence of adoption of unhealthy diets excessive in calories and salt (NaCl) as well as devoid in pivotal micronutrients such as potassium (K) and magnesium (Mg). Education-based programs aiming to encourage healthy food knowledge and behaviors are crucial at a young age, and for this purpose, convenient ways to assess daily dietary intake are warranted. We therefore attempted to evaluate the dietary intake of Okinawan schoolchildren in Japan by analyzing a series of biomarkers in morning spot urine samples and explore whether these biomarkers correlate with body weight and a series of metabolic parameters. We enrolled 98 third-grade elementary schoolchildren in Okinawa, Japan. Morning spot urine samples were collected and analyzed using high-performance liquid chromatography (HPLC) to assess dietary intake. We found that estimated daily NaCl intake was higher in obese/overweight children as compared to healthy-weight children (p = 0.0001). There was also a significant positive correlation between body mass index (BMI) and NaCl intake (Spearman) (ρ = 0.45, p ρ = −0.27, p = 0.01). Furthermore, Na/K ratio was higher in samples collected on Monday (weekend) as compared to samples collected on Thursday or Friday (weekday) (p Conclusion: Via the use of morning spot urine analyses, our results show that NaCl intake was associated with obesity, and Mg excretion negatively correlated with BMI in Japanese schoolchildren, highlighting the potential role of these micronutrients in maintaining a healthy body weight. What is Known:•Overweight and obesity are largely due to excessive consumption of calories and positively correlated with salt (NaCl) intake.•Spot urine methods are convenient for assessing the nutritional needs and targeting prevention programs in children. What is New:•Utilizing morning spot urine analyses, estimated NaCl intake is positively correlated and Mg/Cr negatively correlated with BMI in Okinawan schoolchildren.•As estimated via morning spot urine samples, a greater proportion of children likely exceeds the recommended NaCl intake on the weekend as compared to weekday.

Managing inflammatory bowel disease (IBD) is a major challenge for physicians and patients during the COVID-19 pandemic. To understand the impact of the pandemic on patient behaviors and disruptions in medical care, we used a combination of population-based modeling, system dynamics simulation, and linear optimization. Synthetic IBD populations in Tokyo and Hokkaido were created by localizing an existing US-based synthetic IBD population using data from the Ministry of Health, Labor, and Welfare in Japan. A clinical pathway of IBD-specific disease progression was constructed and calibrated using longitudinal claims data from JMDC Inc for patients with IBD before and during the COVID-19 pandemic. Key points considered for disruptions in patient behavior (demand) and medical care (supply) were diagnosis of new patients, clinic visits for new patients seeking care and diagnosed patients receiving continuous care, number of procedures, and the interval between procedures or biologic prescriptions. COVID-19 had a large initial impact and subsequent smaller impacts on demand and supply despite higher infection rates. Our population model (Behavior Predictor) and patient treatment simulation model (Demand Simulator) represent the dynamics of clinical care demand among patients with IBD in Japan, both in recapitulating historical demand curves and simulating future demand during disruption scenarios, such as pandemic, earthquake, and economic crisis.

Aims: The ankle-brachial index (ABI) can be a prognostic marker for chronic kidney disease (CKD) in Western populations. Since there is little relevant evidence for Asian populations, we investigated the relationship between ABI and the risk of incident CKD in a general Japanese population. Methods: The cohort included 5,072 participants aged 30–79 without a history of renal disease or cerebro-cardiovascular disease. Incident CKD, defined as an estimated glomerular filtration rate < 60 (mL/min/1.73 m2) and/or proteinuria (≥ 1 + on urine dipstick), was compared among participants grouped according to baseline ABI: 0.90–0.99, 1.00–1.09, 1.10–1.19, 1.20–1.29, and 1.30–1.39. Hazard ratios for incident CKD were estimated using a Cox proportional hazards model, with the ABI 1.10–1.19 group serving as the reference. Results: The CKD incidence rate (/100 person-years) was 1.80 during the mean follow-up period of 5.1 years. The CKD incidence rate was 3.04 in the ABI category 0.90–0.99, 1.58 in ABI 1.00–1.09, 1.72 in ABI 1.10–1.19, 2.01 in ABI 1.20–1.29, and 3.33 in ABI 1.30–1.39. The hazard ratios for developing CKD were 2.14 (95% confidence interval 1.16–3.92) in ABI 0.90–0.99, 1.08 (0.83–1.41) in ABI 1.00–1.09, 1.03 (0.83–1.29) in ABI 1.20–1.29, and 1.37 (0.77–2.47) in ABI 1.30–1.39, after adjusting for age, sex, systolic blood pressure, diabetes, and other confounding factors. Conclusions: In a general Japanese population, an ABI of 0.90–0.99 was associated with an increased risk of incident CKD, independent of traditional cardiovascular risk factors.

Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.

Cholesteryl ester (CE) is an ester of cholesterol and fatty acid (FA). Plasma CE reflects complicated metabolisms of cholesterol, phospholipids, lipoproteins, and dietary FAs. An informatics approach could be useful for analysis of the CE species. In this study, two basic dimension reduction methods, principal component analysis (PCA) and factor analysis, were applied to serum CE species determined by LC-MS/MS in a Japanese population (n = 545). PCA and factor analysis both reflected the size (concentration), food source, fat solubility, and biological aspect of the CE species. In a comparison between PCA (PC4) and factor analysis (factor 4), the latter was found to be more suggestive from a biological aspect of n-6 FAs. Cholesteryl docosahexaenoate (DHA) was found to be unique by a factor analysis, possibly relevant to the unique accumulation of DHA in the brain. An informatics approach, especially factor analysis, might be useful for the analysis of complicated metabolism of CE species in the serum.

Objective: The present cross-sectional study investigated the relationship between serum 25-hydroxyvitamin D-3 (25[OH]D-3) levels and the presence of poor sleep quality in a community-based Japanese adult population. Methods: Poor sleep quality, defined as poor subjective sleep quality and/or use of sleep medications, was assessed using a self-administered questionnaire. The prevalence of poor sleep quality was compared among 512 Japanese participants aged 35-79 years, based on serum 25(OH) D-3 levels, which were determined using tandem mass spectrometry. A logistic regression model was used to calculate the odds ratios (ORs) for the presence of poor sleep quality in each group with the highest quartile of 25(OH) D-3 serving as the reference group. Results: Poor sleep quality was reported by 33.2% of the total study population. The prevalence of poor sleep quality was higher in the first quartile group (25[OH] D-3: 2.08-18.13 ng/mL) than in the second, third and fourth quartile groups (18.14-23.07 ng/mL, 23.08-28.32 ng/mL, and 28.33-78.83 ng/mL, respectively). The ORs for poor sleep quality were 1.86 (95% confidence interval, 1.08-3.20) for the first quartile group, 0.73 (0.41-1.29) for the second quartile group, and 0.73 (0.42-1.27) for the third quartile group after adjusting for age, sex, and sociodemographic, lifestyle, physical and environmental factors, while the ORs were 1.68 (0.96-2.95), 0.69 (0.39-1.24), and 0.65 (0.37-1.15) after further adjustment for overall health status and depression status. Conclusions: The first quartile group of serum 25(OH) D-3 was associated with the presence of poor sleep quality. (c) 2019 Elsevier B.V. All rights reserved.

Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r = − 0.307, p Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.

Background: Evidence for what diseases occur more commonly in older people from a poor residential environment (PRE) is limited. Objective: We investigated characteristics, especially the underlying reason (disease) for visiting an emergency department (ED), of older people from a PRE in ED settings. Methods: A cross-sectional study was conducted on people aged ≥65 years who presented to the EDs of 2 hospitals in Okinawa, Japan, between 2015 and 2019. PRE cases were identified by searching relevant words, such as a house overflowing with garbage from hoarding or housing squalor (gomi-yashiki in Japanese), in electric medical records. Controls (2 controls per case) were randomly selected from those without a PRE, with both living at home and matching each PRE case for age and sex. Characteristics of interest between cases and controls were compared using a χ2 test. Results: PRE cases (n = 67), compared with controls (n = 134), were more often transported by ambulance (79.1% vs. 61.9%; p = 0.01). A family member or relative (43.4%) or professional supporter (20.8%) called an ambulance for most PRE cases. PRE cases were more likely to visit the ED due to injury/fracture (16.4% vs. 8.2%), rhabdomyolysis (11.9% vs. 1.5%), undernutrition/dehydration (10.4% vs. 1.5%), and cancer (9.0% vs. 5.2%) than controls (p < 0.001). PRE cases had a higher prevalence of being underweight (35.4% vs. 14.9%), dementia (41.8% vs. 16.4%), decubitus ulcer (29.9% vs. 8.2%), living alone (73.1% vs. 23.1%), and receiving public welfare assistance (35.8% vs. 9.0%) than controls (all p ≤ 0.001). Conclusion: In EDs, older people from a PRE exhibited certain diseases and characteristics.

In Western populations, fecal concentrations of short-chain fatty acids (SCFAs) are positively correlated with the prevalence of obesity. However, gut microbiota involved in the production of SCFA varies between races. Our purpose was to investigate the associations between fecal SCFAs and the prevalence of obesity in a community-based Japanese population. We classified a total of 568 participants aged ≥18 into four quartiles of fecal concentrations of SCFA subtypes (acetate, butyrate, and propionate) and total SCFAs to compare the prevalence of obesity, defined as a body mass index ≥ 25.0 kg/m2. Using the first quartile SCFA group as a reference, the prevalence ratios of obesity were calculated for each SCFA group through a log-binomial regression model adjusted for major potentially confounding factors including age, sex, exercise habits, total energy intake, and total dietary fiber intake. In the study population, the prevalence of obesity was 35.8%. The prevalence ratios (95% confidence intervals) of obesity in the second, third, and fourth quartile groups of fecal total SCFAs were 1.30 (0.89-1.89), 1.74 (1.23-2.47) and 1.70 (1.19-2.41), respectively, after adjusting for the confounders. Similar positive associations were observed for every subtype. The prevalence ratios (95% confidence intervals) in the fourth quartile groups of fecal acetate, butyrate, and propionate were 1.41 (1.02-1.97), 2.16 (1.49-3.14), and 1.97 (1.35-2.89), respectively, after adjusting for the confounders. In conclusion, our results demonstrated that fecal SCFA concentrations of every subtype were positively associated with the prevalence of obesity in a community-based Japanese population.

Whether the source of dietary protein intake is related to appendicular skeletal muscle mass (AMM) and muscle mass (MM) remains unclear. We conducted this cross-sectional study of 277 residents (115 men, 162 women) aged &ge, 65 years in Japan to examine the association of the amount of dietary protein intake with AMM and MM. We measured dietary protein intake using a brief self-administered diet history questionnaire. AMM and MM were assessed based on bioelectrical impedance. Multivariable linear regression analyses were used to estimate &beta, coefficients that were adjusted for potential confounders. Among Japanese women aged &ge, 75 years, but not among women aged 65&ndash, 74 years, dietary animal protein intake was significantly associated with AMM (&beta, (95% confidence interval (CI)): 0.25 (0.10, 0.40)) and MM (&beta, (95% CI): 0.40 (0.16, 0.64)). However, dietary vegetable protein intake was not associated with AMM (&beta, (95% CI): &minus, 0.17 (&minus, 0.74, 0.41)) and MM (&beta, 0.30 (&minus, 1.23, 0.63)). Furthermore, in men aged &ge, 65 years, dietary protein intake was not associated with AMM or MM. In conclusion, dietary animal protein intake, but not vegetable protein intake, were positively associated with AMM and MM among this population of Japanese women aged &ge, 75 years.

Background:Lower socioeconomic status (SES) may be related to inactivity lifestyle; however, the association between SES and physical inactivity has not been sufficiently investigated in Japan., Methods:The study population is the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2,609 adults. Physical activity was assessed by physical activity index (PAI) calculated from activity intensity and time. The lowest tertile of PAI for each 10-year age class and sex was defined as physical inactivity. Multivariable logistic regression analyses were conducted to examine the association of SES (employment status, educational attainment, living status, and equivalent household expenditure (EHE)) with physical inactivity., Results:In the distribution of PAI by age classes and sex, the highest median PAI was aged 30-39 years among men (median 38.6), aged 40-49 years among women (38.0), and median PAI was decreased with increasing age. Multivariable-adjusted model shows that not working was significantly associated with physical inactivity after adjustment for age in all age groups and sexes. Not living with spouse for adult women and elderly men was significantly associated with physical inactivity compared to those who living with spouse. However, neither educational attainment nor EHE had any significant associations with physical inactivity., Conclusions:The result indicated that physical inactivity was associated with SES in a general Japanese population. SES of individuals need to be considered in order to prevent inactivity lifestyle.

Background and Aims: The nature of the relationship between serum adiponectin and pancreatic beta-cell function remains controversial. In this community-based study, we investigated the association between serum high-molecular-weight (HMV) adiponectin and proinsulin levels in a general Japanese population. Methods: In this cross-sectional study, we analyzed data for residents aged between 35 and 79 years in a rural community in Hokkaido, Japan. A total of 488 participants (53.9% women) without insulin and/or oral hypoglycemic agents were enrolled. Univariate linear regression analysis was performed to examine the association between ln-transformed serum HMV adiponectin and ln-transformed proinsulin levels. Multiple linear regression analysis was used to calculate coefficients after adjusting for age and sex. Estimates included partial regression coefficient (β) and corresponding 95% CI. Results: Serum HMW adiponectin was significantly inversely associated with proinsulin by univariate linear regression analysis (β: −0.36; 95% CI: −0.44 to −0.29). Multiple linear regression analysis showed that HMW adiponectin was inversely associated with proinsulin after adjusting for age and sex (β: −0.37; 95% CI: −0.46 to −0.28). When the participants were classified into two groups by median BMI, serum insulin or HOMA-IR, similar inverse associations were observed after adjusting for age and sex irrespective of the levels of each factor. Furthermore, these inverse associations were observed in both participants with and without diabetes. Conclusions: HMW adiponectin level was inversely associated with proinsulin level in a general Japanese population. HMW adiponectin may have a protective effect on beta-cell function. Disclosure A. Nakamura: None. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Ukawa: None. K. Nakamura: None. T. Nakagawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk A/S, Sanofi. Consultant; Self; Astellas Pharma Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Medscape, Medtronic, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. A. Tamakoshi: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd. Funding Integration Research for Agriculture and Interdisciplinary Fields (538261); Japan Society for the Promotion of Science (JP26670322)

Background: The causes of pancreatic beta-cell dysfunction include glucose toxicity and lipotoxicity. Basic research has suggested that free fatty acids (FFAs) damage pancreatic beta-cells. However, the relationship between FFAs and pancreatic beta-cell dysfunction has not been clarified in humans. Therefore, we investigated the relationship between the serum concentrations of FFA and proinsulin (PI), a marker of pancreatic beta-cell dysfunction, in a general Japanese population. Methods: This was a cross-sectional study of 489 people (226 men, 263 women; age 35-79 years) from a rural community in Hokkaido, Japan who were not taking diabetic medication and who provided fasting blood samples. Serum PI was measured by a radioimmunoassay, and was compared among quartiles defined with respect to FFA concentration. Because the serum FFA and PI levels showed skewed distributions, univariable and multivariable regression analyses were performed after logarithmic transformation. Results: PI, age, body mass index, and fasting blood glucose and insulin were positively associated with serum FFA quartile: for PI, median (first quartile, third quartile): Q1 8.1 (6.0, 11.7), Q2 8.5 (6.9, 13.1), Q3 9.2 (6.7, 14.5), and Q4 11.2 (7.6, 16.7); p Conclusion: Serum FFA was positively associated with PI in a general Japanese population. Thus, FFA may play a role in pancreatic beta-cell dysfunction. Disclosure K. Chiba: None. A. Nakamura: None. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Ukawa: None. K. Nakamura: None. T. Nakagawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk A/S, Sanofi. Consultant; Self; Astellas Pharma Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Medscape, Medtronic, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. A. Tamakoshi: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd.