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Introduction: The efficacy and safety of oral semaglutide, the first glucagon-like peptide 1 receptor agonist available in tablet form for the treatment of type 2 diabetes, were established in the phase 3a PIONEER program. However, evidence regarding the titration of oral semaglutide in real-world clinical settings remains insufficient. This study aimed to elucidate the therapeutic advantages of escalating the dose of oral semaglutide from 7 to 14 mg through clinical data analysis. Methods: This retrospective observational study was conducted at a single center in Japan, focusing on adults with type 2 diabetes who were initiated on 14 mg oral semaglutide. The primary endpoint was the alteration in HbA1c levels 24 weeks after the initial prescription of 14 mg oral semaglutide. Secondary endpoints included changes in metabolic parameters and the incidence of adverse events. Results: Data from 66 patients who met the inclusion criteria were analyzed. The mean change in HbA1c levels from baseline to 24 weeks following dose escalation was − 0.5 ± 0.8% [from 7.4 ± 1.0% at baseline to 7.0 ± 0.9% at 24 weeks (p < 0.01)]. Moreover, a significant reduction in body weight of − 2.0 ± 4.4 kg was observed at 24 weeks [from 90.0 ± 20.5 kg at baseline to 88.2 ± 21.4 kg at 24 weeks (p < 0.01)], with 41% of patients achieving at least a 3% reduction compared to baseline. Gastrointestinal disorders emerged as the most prevalent adverse event (10.6%), particularly nausea (7.6%), although predominantly of mild or moderate severity, with no instances of serious adverse events necessitating drug discontinuation. Conclusion: Escalating the dose of oral semaglutide to 14 mg could be an effective approach for enhancing glycemic control and managing body weight in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions Normoglycaemia was achieved in a significant proportion of Japanese participants with type 2 diabetes in two phase 3 studies of tirzepatide. This post hoc exploratory analysis aimed to identify predictive factors associated with normoglycaemia achievement.SURPASS J‐mono and SURPASS J‐combo study data were pooled for this analysis. Characteristics of participants in whom normoglycaemia [glycated haemoglobin (HbA1c) <5.7%] was achieved were summarized. Logistic regression analyses were performed with HbA1c <5.7% achievement as the target variable.Of 912 participants, normoglycaemia was achieved in 553 (60.6%) following 52 weeks of tirzepatide treatment. Overall, the mean (SD) age was 56.7 (10.6) years and mean diabetes duration was 7.7 (6.0) years, and 76% of participants were men. Mean (SD) change from baseline in HbA1c and bodyweight was −2.87% (0.95) versus −2.47% (1.1) and −10.30 (5.8) kg versus −3.75 (4.3) kg for participants in whom normoglycaemia was and was not reached, respectively. Multivariate regression analyses showed that lower baseline body mass index, shorter disease duration and lower baseline HbA1c were significantly associated with higher rates of normoglycaemia achievement (p = 0.009, p = 0.008, p < 0.001, respectively) as was a tirzepatide dose of 10 or 15 mg compared with 5 mg (p < 0.001). The highest percentage of participants in whom normoglycaemia (94%) was achieved were those with lower baseline HbA1c (<8%) and the greatest weight reduction (≥15%).Baseline HbA1c and body mass index, disease duration and the tirzepatide treatment group were shown to be predictive factors for achieving normoglycaemia. A lower baseline HbA1c was most strongly associated with normoglycaemia achievement. [ABSTRACT FROM AUTHOR]

Background: Maximum phonation time (MPT) is used to assess speech and other oral rehabilitation‐related issues. Various factors contribute to MPT decline in older individuals. Although the impact of physical frailty on MPT has been suggested, this has not been conclusively determined. Objective: To examine the relationship between MPT and physical frailty in community‐dwelling individuals aged ≥60 years who were independently mobile. MPT‐associated factors were investigated. Methods: This cross‐sectional study analysed the clinical data of 122 patients (age [interquartile range]: 80.0 [74.0–83.0] years) without dementia who visited a neurology department between 1 February 2021 and 31 January 2023. Investigated factors included age, sex, weight, height, body mass index, smoking history, grip strength, functional independence measure, vital capacity, oral diadochokinesis, MPT and the Japanese Cardiovascular Health Study score. Physical frailty was assessed based on the total score from five items (weight loss, weakness, exhaustion, slowness and low physical activity). The relationship between MPT and physical frailty was examined using Spearman's rank correlation coefficient and hierarchical multiple regression analysis. Results: The MPT was negatively correlated with age (r = −0.347, p <.01) and physical frailty (r = −0.681, p <.01) and positively correlated with vital capacity (r = 0.474, p <.01) and height (r = 0.248, p <.01). The hierarchical multiple regression analysis, conducted with MPT as the dependent variable, demonstrated that physical frailty (β = −.59, 95% confidence interval: −0.74 to 0.43, p <.001) had a strong influence on MPT. Conclusion: In older individuals, MPT is associated with physical frailty. When assessing MPT in clinical settings, it is advisable to perform a concurrent assessment of physical frailty. [ABSTRACT FROM AUTHOR]

Body mass index (BMI) is routinely used to ascertain health status, including activities of daily living (ADLs); however, the associations of ADLs with height and weight in older adults have not been elucidated. Therefore, we cross-sectionally investigated the correlations between ADLs and height, weight, and BMI in 155 participants aged 82 to 103 years and characterized the naïve Bayesian prediction for ADLs. Activities of daily living showed a significant negative correlation with height and weight and a positive correlation with age. In males, a shorter height was associated with an increased risk of falling and disability in phone calling independently, and losing weight was associated with an increased risk of disability in going out. Combining age, weight, and height improved the area under the receiver operating characteristic curve in the prediction of disability in going out and phone calling independently in males. Therefore, height and weight, not BMI, are potential predictors of ADL decline. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups. Methods: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves. Results: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction. Discussion: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population. [ABSTRACT FROM AUTHOR]

(1) Background: The number of severely obese patients worldwide is rapidly increasing. Recently, novel therapeutic approaches, such as bariatric surgery or GLP-1 receptor agonists, have emerged, bringing about a paradigm shift in this field. However, these therapies sometimes face challenges, such as peri-surgical complications or supply shortages. Mazindol, which is an appetite suppressant approved decades ago in Japan, remains a valuable option. In this study, we investigated the effectiveness of mazindol in reducing body weight in 147 patients, and we examined the factors influencing said effectiveness. (2) Methods: The patients were divided into four groups based on the treatment cycles they underwent: 1 cycle, 2 cycles, 3–5 cycles, and over 6 cycles. We compared the changes in body weight before and after the treatment among these four groups. Additionally, we sought to identify the factors correlated to the effectiveness of mazindol. (3) Results: The change in body weight was more pronounced in the group which underwent 3–5 cycles compared to the groups which underwent 1 cycle and 2 cycles; this change was also more pronounced in the group which underwent over 6 cycles compared to those which underwent 1 cycle. Furthermore, we observed a significant correlation between the initial body weight and the extent of body weight change. (4) Conclusions: Mazindol demonstrated effectiveness in reducing the body weight of patients in a cycle-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is a multifactorial syndrome leading to progressive functional impairment. How cachexia affects the treatment course of chemotherapy in patients with pancreatic cancer has not been well understood. Methods: This is an exploratory, retrospective, observational cohort study using the Japanese medical claims database from Medical Data Vision Co., Ltd. The study population included patients diagnosed with pancreatic cancer in whom first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) was initiated between October 1, 2018, and September 30, 2020. In this study, we defined patients with cancer cachexia as those who had a weight loss of ≥ 5% in the preceding 6 months. The primary outcome was time-to-treatment failure (TTF). The observation period was six months from the initiation of first-line FFX or GnP treatment. Results: A total of 1897 patients (421 patients into the cachexia group; 1476 patients into the non-cachexia group) were analyzed in this study. The median TTF was 121 days (95% confidence interval [CI] 94–146) in the cachexia group and 143 days (95% CI 134–152) in the non-cachexia group. The hazard ratio for TTF of the cachexia versus non-cachexia group was 1.136 (95% CI 0.979–1.319). The median number of doses was two doses fewer in the cachexia group than in the non-cachexia group for both FFX and GnP. Conclusion: Cancer cachexia was suggested to be associated with shorter TTF and a reduced number of doses in patients with pancreatic cancer who received first-line FFX or GnP treatment. Clinical Trial Registration clinicaltrials.jp: UMIN000045820. [ABSTRACT FROM AUTHOR]

Japan has approved the weight-loss drug semaglutide, known as Wegovy, for chronic weight management. The drug is covered by Japan's national universal health insurance, but there are stringent prescription restrictions. Semaglutide is indicated for adult patients with hypertension, hyperlipidemia, or type 2 diabetes who cannot achieve sufficient effect through dietary therapy and physical activity. However, there are concerns about limited patient access to the drug due to restrictions on prescribing physicians and the requirement for patients to undergo dietary therapy and physical activity for six months prior to receiving the drug. Other Asian countries, such as China, are expected to introduce the drug soon. [Extracted from the article]

Introduction: The real-world SPARTA Japan study confirmed the effectiveness and safety of the fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) once daily over 6 months in Japanese people with type 2 diabetes (T2D). This post hoc analysis examined the impact of participant characteristics on the achievement of age-defined glycaemic targets with iGlarLixi therapy. Methods: The retrospective, observational SPARTA Japan study included adults with T2D who initiated iGlarLixi. In this analysis, data from insulin-naïve and insulin-experienced participants were separately assessed to compare glycated haemoglobin (HbA1c), body weight and safety outcomes between those who achieved ('achieved' group) and those who did not achieve ('not-achieved' group) age-defined glycaemic targets after 6 months of iGlarLixi. The not-achieved group was further stratified by whether or not their iGlarLixi dose was increased during treatment. Results: In total, 418 participants were included in this analysis (138 insulin naïve and 280 insulin experienced). Among both insulin-naïve and insulin-experienced participants, those in the achieved group were older and had lower baseline HbA1c than those in the not-achieved group. Compared with the not-achieved group, the achieved group showed significantly greater HbA1c reductions from baseline (in both insulin-naïve and insulin-experienced participants) and significantly greater body weight reductions (in insulin-naïve participants), despite some participants in the not-achieved group receiving significantly higher insulin glargine doses than those in the achieved group. In both insulin-naïve and insulin-experienced participants, the incidence of hypoglycaemia and gastrointestinal-related adverse events was similar in the achieved and not-achieved groups. In a multivariate analysis, glycaemic target achievement was significantly more likely in older individuals and those who lost weight during iGlarLixi treatment. Conclusions: Achievement of age-defined glycaemic targets with iGlarLixi treatment for 6 months was significantly affected by increased age and body weight loss, regardless of prior insulin exposure. Trial Registration: UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021. Plain Language Summary: iGlarLixi is an injectable product used to treat type 2 diabetes that contains a fixed combination of two drugs, insulin glargine (at a concentration of 100 U/mL) and lixisenatide. The SPARTA Japan study investigated the effectiveness of controlling blood glucose levels and the safety of iGlarLixi in Japanese people when taken once daily for over 6 months as part of their routine medical care. The analysis reported in this article looked back at data from SPARTA Japan to assess whether certain characteristics of the people who took part in the study affected how well blood glucose targets were met. People who had previously taken insulin and those who had not were identified, and their results were assessed separately. The people were divided into those who had met their blood glucose level target (with the target defined as the glycated haemoglobin level for each person based on their age) and those who had not met their target. It was found that people who achieved their blood glucose target while receiving iGlarLixi were more likely to be older, to have had a lower glycated haemoglobin level before starting iGlarLixi, and to have lost weight during treatment than those who did not achieve their target, whether or not they had previously been treated with insulin. Side effects of excessively low blood glucose levels or gastrointestinal upset with iGlarLixi treatment occurred in a similar number of people who achieved or did not achieve their blood glucose target. [ABSTRACT FROM AUTHOR]

Background: Physical frailty accelerates the timing of both subsequent disability and death; however, evidence regarding the impact of frailty on the period from disability onset to death and sex differences of this impact is lacking. The aim of this study was to examine the relationship among physical frailty, disability, death, and sex differences. Methods: This Japanese cohort study included 10,524 community‐dwelling people aged ≥65 years. Physical frailty was operationalized by key phenotypes as per Fried's criteria (slowness, weakness, exhaustion, weight loss, and low activity) at baseline. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for disability onset and post‐disability survival according to the frailty status. Results: During a 5‐year follow‐up, the risk of disability onset for pre‐frailty (HR: 1.74, 95% CI: 1.51–2.00) and frailty (HR: 3.27, 95% CI: 2.77–3.87) were significantly higher than that for robust people. Furthermore, among participants who developed disabilities within 5 years (n = 1481), the risk of post‐disability death for pre‐frailty was not different from that for robust (HR: 1.49, 95% CI: 0.99–2.24), but frailty showed a higher risk of post‐disability death than did robust people. (HR: 1.75, 95% CI: 1.13–2.72). In the sex‐stratified analysis, although the female group showed no association between frailty status and post‐disability death (HR: 1.21, 95% CI: 0.63–2.33 in pre‐frailty; HR: 1.24, 95% CI: 0.60–2.57 in frailty), the male group showed higher risk of post‐disability death in both pre‐frailty (HR: 1.74, 95% CI: 1.03–2.96) and frailty (HR: 2.32, 95% CI: 1.32–4.09). Conclusions: Physical frailty shortens the period from disability onset to death. Additionally, the impact of frailty on post‐disability death is greater for males than for females. Our findings suggest that physical frailty is an important clinical indicator distinct from disability and that interventions to prevent and address frailty in men need further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Despite the increasing performance of laparoscopic proximal gastrectomy (LPG) for proximal gastric cancer and esophagogastric junction cancer, the benefit of LPG over laparoscopic total gastrectomy (LTG) remains to be established. Therefore, this study was conducted to compare postoperative outcomes between LPG and LTG. Methods: Data from 141 patients who underwent LPG or LTG for gastric neoplasm with curative intent between 2016 and 2022 were retrospectively reviewed. Clinicopathological findings, body weight changes, and serological nutritional markers during the postoperative course were evaluated. Results: LPG and LTG were performed in 78 patients and 63 patients, respectively. Patients' characteristics did not differ; however, tumor stages in patients who underwent LTG were more advanced than those who underwent LPG. The mean (± standard deviation) weight loss rate after 1 year was −13.5 (±6.9)% and −18.7 (±6.6)% for LPG and LTG, respectively (p <.01). LTG (OR: 3.326, p <.01), pT disease (OR: 3.000, p =.01), pN disease (OR: 2.708, p =.02), and postoperative chemotherapy (OR: 2.488, p =.05) were correlated with severe weight loss (16% or more) 1 year after surgery, then multivariate analysis identified LTG as an independent factor (p =.01). The mean (± standard deviation) serum total protein level of LPG was significantly higher than that of LTG at 3 months (6.8 ± 0.5 vs. 6.6 ± 0.4 g/dL, p =.02) and 1 year (6.9 ± 0.4 vs. 6.7 ± 0.5 g/dL, p =.01) postoperatively. No difference was observed in postoperative serum hemoglobin and albumin levels. Conclusion: LPG more improved postoperative weight loss than LTG. [ABSTRACT FROM AUTHOR]

We developed a standalone smartphone app for weight management for middle-aged people. Among people living in Okinawa, Japan, participants were required to have BMI 25 or greater at the time of online registration. The intervention was a 3-month duration using the following four functions: recording of walking steps, diet content and bodyweight, and reading basic health knowledge. Among 87 participants who met our study criteria, 47 (54%) adhered to the program to endline and 28 participants (60%) lost body weight (0.3-5.6 kg loss: 0.3-7.1% loss). Frequency of recording walk steps was associated with BMI reduction with beta coefficient of 0.00847 (95% confidence interval, −0.01595 to −0.00099). No cases of adverse health events were reported during our study period. A standalone app can play an important role in weight management among middle-aged people with overweight/obesity. [ABSTRACT FROM AUTHOR]

Aim: To fill the knowledge gap regarding weight change and the onset of disability in community‐dwelling Japanese older adults, we investigated the potential effects of rapid weight change on disability risk as defined by Japan's long‐term care insurance (LTCI) system. Methods: We analyzed data from a longitudinal study of 10 375 community‐dwelling older Japanese adults (≥65 years) who were not LTCI needs certified at baseline and joined the study from 2002 to 2005. Weight change (percentage) was calculated by subtracting participants' weight in the previous year from that measured during a physical examination at study commencement. The five weight‐change categories ranged from sizable weight loss (≤ −8.0%) to sizable weight gain (≥ +8.0%). Disability was defined according to LTCI certifications at follow‐up. Hazard ratios (HRs) and 95% confidence intervals were calculated for new‐onset disability using a Cox proportional hazards model that fitted the proportional subdistribution hazards regression model with weights for competing risks of death. Results: During the mean 10.5‐year follow‐up, 2994 participants developed a disability. Sizable weight loss (HR [95% confidence intervals], 1.41 [1.17–1.71]) and weight loss (1.20 [1.05–1.36]) were significant predictors of disability onset. Sizable weight gain (1.45 [1.07–1.97]) corresponded to severe disability. Stratified analyses by lifestyle and initial body mass index categories revealed more pronounced associations between weight change and disability risk in the unhealthy lifestyle and below initial normal body mass index groups. Conclusions: Rapid and sizable weight gain could be additional criteria for disability risk in older adults. Geriatr Gerontol Int 2023; 23: 809–816. [ABSTRACT FROM AUTHOR]

Aims: To determine the association between the magnitude of weight loss and incidence of remission according to baseline characteristics in patients with diabetes in clinical settings. Methods: In total, 39 676 Japanese patients with type 2 diabetes aged ≥18 years with glycated haemoglobin (HbA1c) ≥6.5% and/or glucose‐lowering drug prescription were identified from databases of specialists' clinics from 1989 and followed until September 2022. Remission was diagnosed as maintaining HbA1c <6.5% at least 3 months after cessation of a glucose‐lowering drug. Factors associated with remission were evaluated by logistic regression analysis according to weight change in 1 year (i.e. ≥10%, 7.0‐9.9%, 3.0‐6.9% reduction, <3% change and ≥3.0% increase). Results: During the study period, 3454 remissions occurred. The rates of remission were higher in the group with the greatest reduction of body mass index (BMI) in any category examined (i.e. baseline BMI, HbA1c, duration of diabetes and treatment). The incidences of remission per 1000 person‐years were about 25 and 50, respectively, for those with BMI ≥22.5 and reductions in BMI of 7.0‐9.9% and ≥10% in 1 year. Remissions per 1000 person‐years were 99.2 and 91.8, respectively, for those with baseline HbA1c of 6.5‐6.9 and a 10% BMI reduction and those not taking glucose‐lowering drugs accompanied by a 10% BMI reduction. Conclusions: Modest weight losses of 3.0‐7.9% were significantly associated with remission, but a minimum of 10% weight loss would be required in addition to an early diagnosis to achieve a 10% remission rate in clinical settings. Our results implied that remission may be expected with a relatively lower BMI in an Asian population compared with that was reported in Western populations if accompanied by weight loss. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Insufficient evidence exists on the sex‐specific associations of body mass index (BMI) and weight change through midlife with dementia incidence, especially in Asian populations. METHODS: For 37,414 Japanese residents aged 40 to 59 years, BMIs at baseline (year 1990 or 1993) and 10‐year follow‐ups were obtained. Weight changes between baseline and 10‐year follow‐ups were determined. Disabling dementia incidence from 2006 to 2016 was ascertained using long‐term care insurance (LTCI) certifications. Hazard ratios (HRs) were computed. RESULTS: Increased dementia risk was observed with obesity at baseline and with underweight at 10‐year follow‐ups. Weight loss after baseline was at greater risk than weight gain. No sex difference was observed. DISCUSSION: In both sexes, obesity in midlife increased the risk of developing dementia with increasing impacts of weight loss after midlife. A healthy body weight throughout adulthood is beneficial for dementia prevention. Highlights: Obesity in midlife is a risk factor for incident dementia.Weight loss is a bigger risk factor than weight gain in later midlife.Association of BMI and weight change in midlife with dementia does not vary by sex. [ABSTRACT FROM AUTHOR]

Polypharmacy, which refers to the situation of a patient taking more medications than is clinically necessary, has become a major problem in recent years. Although the effects of medications on pressure ulcers have been reported, there are no reports on the impact of the total number of medications on pressure ulcers. The purpose of this study was to investigate the effect of number of medications on the severity of pressure ulcers. Participants included 94 patients who were admitted to Chiba University Hospital with pressure ulcers between April 2013 and March 2021. Univariate analysis identified ulcer depth, weight loss and anticoagulant use to be factors that contributed to the severity of pressure ulcers. Multiple regression analysis was performed for six variables, namely, the number of medications, ulcer depth, weight loss and anticoagulant use, as well as diabetes status and total serum protein level, which have been reported to be associated with pressure ulcers in previous studies. The following independent risk factors were identified: weight loss (β 0.207, 95% confidence interval [CI] 0.700–3.193; p = 0.003), anticoagulant use (β 0.161, 95% CI 0.271–3.088; p = 0.020) and ulcer depth (β 0.719, 95% CI 7.172–10.329; p < 0.001). The number of medications was not a significant factor. This study revealed that the number of medications a patient is taking does not affect the severity of pressure ulcers. The findings should provide useful information for the management of pressure ulcers. [ABSTRACT FROM AUTHOR]

Linear phase shifting transformer is a new type of phase shifting transformer with the advantages of simple winding structure, easy modularity, and the ability to shift phase at any angle. In order to improve the efficiency and power factor of linear phase shift transformer and reduce the weight of the body, based on the equivalent circuit, this paper first, selects the main design parameters of the linear phase shift transformer model as the optimization object, secondly, selects the constraints and objective function applicable to this model, and then, establishes the linear phase shift transformer optimization design model. Finally, a differential evolutionary algorithm with strong global search performance is used to optimize the design parameters. Taking the 1 kW linear phase shifting transformer as an example, the efficiency, power factor, and weight before and after optimization are compared using finite element simulation to verify the effectiveness of the proposed optimization method. The test results of the experimental prototype prove that the proposed method can effectively solve the optimization design problem of linear phase shifting transformers. © 2023 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Rabbit anti-thymocyte globulin (rATG), a therapeutic polyclonal antibody against human T cells, is commonly used in conditioning therapy prior to allogeneic hematopoietic cell transplantation (HCT). Previous studies successfully developed an individualized rATG dosing regimen based on "active" rATG population PK (popPK) analysis, while "total" rATG can be a more logistically favorable alternative for early HCT outcomes. We conducted a novel popPK analysis of total rATG. Methods: Total rATG concentration was measured in adult human-leukocyte antigen (HLA) mismatched HCT patients who received a low-dose rATG regimen (total 2.5–3 mg/kg) within 3 days prior to HCT. PopPK modeling and simulation was performed using nonlinear mixed effect modeling approach. Results: A total of 504 rATG concentrations were available from 105 non-obese patients with hematologic malignancy (median age 47 years) treated in Japan. The majority had acute leukemia or malignant lymphoma (94%). Total rATG PK was described by a two-compartment linear model. Influential covariate relations include ideal body weight [positively on both clearance (CL) and central volume of distribution], baseline serum albumin (negatively on CL), CD4+ T cell dose (positively on CL), and baseline serum IgG (positively on CL). Simulated covariate effects predicted that early total rATG exposures were affected by ideal body weight. Conclusions: This novel popPK model described the PK of total rATG in the adult HCT patients who received a low-dose rATG conditioning regimen. This model can be used for model-informed precision dosing in the settings with minimal baseline rATG targets (T cells), and early clinical outcomes are of interest. [ABSTRACT FROM AUTHOR]

This study examined young girls enrolled in preschool to junior high school in Japan to clarify their mothers' influence on their body dissatisfaction and weight loss behaviors. The survey participants comprised 790 Japanese women aged 20 to 55 years (mean age 37.5 years, SD = 6.28 years) with daughters aged 3–14 years enrolled in preschool to junior high school. Results indicated that a mother's pressure affected her daughter's body dissatisfaction and ultimately her weight loss behavior. The association was confirmed in a wide range of ages from preschoolers to junior high school students. It can be suggested that the message from their mothers over a long period may lead to girls' body dissatisfaction and consequently weight loss behavior from a young age. Intervention for body dissatisfaction is needed for mothers and children starting at a very early age stage. [ABSTRACT FROM AUTHOR]

Tranilast (N-3, 4-dimethoxycinnamoyl anthranilic acid) is an orally administered drug with antiallergic properties and approved in Japan and the Republic of Korea for the treatment of asthma and hypertrophic scars. Previous in vitro studies indicated that tranilast reduced fibroid growth through its inhibitory effects on cell proliferation and induction of apoptosis. The objective of this study was to determine the efficacy of tranilast for treatment of human-derived fibroids in a mouse model. SCID mice (ovariectomized, supplemented with estrogen and progesterone) were implanted with fibroid explants and treated for two months with tranilast (50 m/kg/daily) or the vehicle. After sacrifice, xenografts were excised and analyzed. Tranilast was well tolerated without adverse side effects. There was a 37% reduction in tumor weight along with a significant decrease in staining for Ki67, CCND1, and E2F1; a significant increase in nuclear staining for cleaved caspase 3; and reduced staining for TGF-β3 and Masson's trichrome in the tranilast treated mice. There was a significant inhibition of mRNA and protein expression of fibronectin, COL3A1, CCND1, E2F1, and TGF-β3 in the xenografts from the tranilast-treated mice. These promising therapeutic effects of tranilast warrant additional animal studies and human clinical trials to evaluate its efficacy for treatment of fibroids. [ABSTRACT FROM AUTHOR]

The Ethiopian Orthodox Christian (EOC) fasts, although adopted for religious purposes, combines aspects of energy restriction, time-restricted feeding, and a vegan dietary pattern, all of which have been independently associated with weight loss and healthier body composition. However, combined effect of these practices as part of EOC fast remains unknown. This longitudinal study design evaluated the effect of EOC fasting on body weight and body composition. Information on socio-demographic characteristics, physical activity level, and fasting regimen followed was captured through an interviewer-administered questionnaire. Weight and body composition measurements were taken before and at the end of major fasting seasons. Body composition parameters were measured by bioelectrical impedance (BIA), Tanita® BC-418®, Japan). Significant changes in body weight and body composition were observed for both fasts. Significant decreases in body weight (14/44 day fast: − 0.45; P = 0.004/− 0.65; P = 0.004), FFM (− 0.82; P = 0.002/− 0.41; P < 0.0001), and trunk fat mass (− 0.68; P < 0.0001/− 0.82; P < 0.0001) were observed after adjusting for covariates including age, sex, and physical activity. The EOC fasting regimen leads to significant reductions of body weight and compositions. Longer fasting duration led to much higher effects in body weight and body composition and may be non-pharmacological strategy in prevention or treatment of chronic diseases. [ABSTRACT FROM AUTHOR]

Bariatric surgery is performed worldwide to address morbid obesity. The benefits of this surgery are weight loss and a decrease in obesity-related complications. The relationship between metabolic/bariatric surgery and reemployment has been evaluated in Western countries, but few such studies have been performed in Japan because the number of metabolic/bariatric surgeries is small. Only a limited number of Japanese studies have evaluated the effects of bariatric surgery on obesity stigma, which affects employment and advancement opportunities for obese persons and may result in dismissal. We describe a case of bariatric surgery for a 39-year-old man who was dismissed from his job because of morbid obesity. Traditional weight loss methods failed to maintain weight loss and, preoperatively, the patient was receiving treatment for type 2 diabetes, hypertension, and abnormal lipid metabolism. He underwent sleeve gastrectomy and lost 50.4 kg (percent excess weight loss: 68.1%) in the first postoperative year. All medications were stopped after improvement in the results of laboratory blood tests and he was reemployed at 8 months after surgery. Increased social activity associated with employment is a factor in suppressing rebound weight gain after bariatric surgery, and weight loss associated with bariatric surgery helps decrease anti-obesity social stigma. [ABSTRACT FROM AUTHOR]

Affordable and accessible behaviour-based interventions that do not overwhelm or demoralise overweight/obese individuals are needed. Combining clothing with behaviour change techniques might be an option. This is because clothing is a social norm, and clothing and motivation for weight loss are associated with the common desire to look better. Therefore, we conducted a single-blind randomised controlled trial to examine the effect of an intervention that combined behaviour change techniques, including simplified goal setting and self-monitoring, with a body compression corrective garment (BCCG), which exerts continuous but minimal tactile pressure on the hips and abdomen. We enrolled healthy community-dwelling adults with a body mass index ≥ 25 kg/m2 and assigned 35 and 34 participants to the intervention and control groups, respectively. The reduction in body weight was 1.3 kg more in the intervention group than in the control group after the 12-week intervention period (p < 0.05, repeated-measures mixed model). In addition, eating behaviour and body appreciation showed significant improvement in the intervention group compared with the control group. Our newly developed intervention improved eating behaviour and body appreciation and reduced the body weight of overweight/obese participants. Wearing a BCCG seems to facilitate behavioural changes and lead to weight loss. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the pharmacodynamic effects of tirzepatide, a novel dual glucagon‐like peptide‐1 receptor and glucose‐dependent insulinotropic polypeptide receptor agonist, compared with dulaglutide in patients with type 2 diabetes. Materials and Methods: SURPASS J‐mono was a 52‐week, multicentre, randomized, double‐blind, parallel, active‐controlled, Phase 3 study, conducted in Japan. This substudy of SURPASS J‐mono evaluated postprandial metabolic variables and appetite after a meal tolerance test, and body composition measured by bioelectrical impedance analysis. Results: Of 636 participants in SURPASS J‐mono, 48 were included in this substudy and assigned to tirzepatide 5 mg (n = 9), tirzepatide 10 mg (n = 11), tirzepatide 15 mg (n = 9), or dulaglutide 0.75 mg (n = 19). Participants had a mean (standard deviation) age of 58.6 (7.5) years, duration of diabetes of 6.0 (6.3) years, and body mass index of 27.5 (3.5) kg/m2. Mean glycated haemoglobin at baseline was 66 mmol/mol (8.22%). Following a standardized meal test, statistically significant differences in change from baseline in area under the concentration versus time curve from time zero to 6 h after dose for glucose, insulin, glucagon, C‐peptide and triglycerides were observed in all tirzepatide treatment arms, except triglycerides at 10 mg, compared with dulaglutide at Week 32. For body composition, tirzepatide 10 mg and 15 mg resulted in a significant reduction in body weight, and all doses of tirzepatide resulted in a significant reduction in body fat mass at Week 52. Conclusions: Compared with dulaglutide, tirzepatide showed greater potential for normalizing metabolic factors after a standardized meal. Tirzepatide reduced body weight and body fat mass. [ABSTRACT FROM AUTHOR]

In animal husbandry, diets should help in maintaining a healthy body condition, support reproduction, and promote species-specific longevity. It is recommended to feed folivorous primates kept in zoos a high-fiber diet, i.e., leaves, although satisfying such a requirement is challenging in temperate regions because it is difficult to obtain fresh leaves, especially in autumn and winter. As equally important for their appropriate treatment, it is valuable to provide details of clinical reports of medical problems and pathological findings, although such clinical reports are rather limited. Therefore, in foregut-fermenting proboscis monkeys (Nasalis larvatus), we (1) described the individual clinical reports of renal disease and weight loss at the Yokohama Zoological Gardens in Japan, (2) determined the nutritional profile of the diets supplied to these animals because other potential triggers for their renal disease and weight loss could be excluded, (3) modified the diet regimen to minimize weight loss and the development of hypercalcemia and hypophosphatemia, and (4) assessed the effects of such dietary modification by comparing the body weight and the Ca and P concentrations and the Ca/P ratios in the blood before and after diet modification with a comparison of these measurements between zoo and free-ranging individuals. Based on the nutritional profile of the diets, we concluded that the reported cases of renal failure might be caused by consumption of leaves with a Ca/P ratio far above the appropriate level in autumn and winter. Additionally, the dietary modification of minerals and metabolizable energy achieved certain beneficial effects on zoo-kept proboscis monkeys. [ABSTRACT FROM AUTHOR]

Background: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA.Research Question: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP?Study Design and Methods: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline.Results: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity.Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm. [ABSTRACT FROM AUTHOR]

Stroke is a progressive disease with remissions and exacerbations; it significantly reduces the quality of life of patients and their family and caregivers. Primary prevention is necessary to reduce the growing incidence of stroke globally. In this study, we determined the risk factors for cerebral infarction in elderly Japanese residents and proposed a primary care strategy to prevent cerebral infarction. We investigated the relationship between the incidence of cerebral infarction and the results of checkups 10 years ago. Multivariate logistic regression analysis was performed to determine the variables related to the occurrence of cerebral infarction in biochemical tests and questionnaires administered ten years ago. Hypertension and abnormal creatinine levels were related to increased risk of cerebral infarction based on our findings of the health checkups conducted 10 years previously. Furthermore, weight gain or loss of >3 kg over the last year and habit of eating an evening meal within 2 h before going to bed were associated with an increased risk of cerebral infarction based on the questionnaire results from the specific health checkups. Long-term, large-scale prospective studies are required to determine the specific health items related to increased risk of cerebral infarction. [ABSTRACT FROM AUTHOR]

Weight reduction therapy represents a fundamental strategy to prevent nonalcoholic fatty liver disease (NAFLD) in patients with obesity, which may result in liver fibrosis. Histological findings previously demonstrated that weight reduction therapy attenuated NAFLD. The FIB4 index is widely used to assess the status of NAFLD. The present study investigated whether the FIB4 index improved during weight reduction therapy. We used cohort data of the Japan Obesity and Metabolic syndrome Study and examined the correlation between body weight (BW) loss (BW loss) and changes in the FIB4 index (ΔFIB4 index) in patients who successfully reduced their BW by more than 5% from baseline BW after 3, 6, and 12 months (M) of weight reduction therapy. A negative correlation (r = −0.342, p = 0.029) was observed between BW loss and FIB4 index after 3 M, but not after 6 M, whereas a positive correlation (r = 0.298, p = 0.03) was noted after 12 M. These results revealed changes in the correlation between ΔBW loss and ΔFIB4 index during the therapy, mainly due to time-dependent changes in components of the FIB4 index formula. Thus, we concluded that the FIB4 index is useful and reliable to assess liver fibrosis until 3 M during weight reduction therapy. However, after 3 M, we should recognize that the FIB4 index may not reflect liver status. Therefore, it is important to consider this characteristic of the FIB4 index as a limitation when assessing liver fibrosis in obese patients receiving weight reduction therapy. [ABSTRACT FROM AUTHOR]

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking for Saudi T2DM patients. Therefore, the current study aimed to assess the efficacy and safety of EMPA in Saudi patients (n = 256) with T2DM. This is a 12-week prospective, open-label, observational study. Adult Saudi patients with T2DM who had not been treated with EMPA before enrolment were eligible. The exclusion criteria included T2DM patients less than 18 years of age, adults with type one diabetes, pregnant women, paediatric population. The results related to efficacy included a significant decrease in haemoglobin A1c (HbA1c) (adjusted mean difference −0.93% [95% confidence interval (CI) −0.32, −1.54]), significant improvements in fasting plasma glucose (FPG) (−2.28 mmol/L [95% CI −2.81, −1.75]), and a reduction in body weight (−0.874 kg [95% CI −4.36, −6.10]) following the administration of 25 mg of EMPA once daily as an add-on to ongoing antidiabetic therapy after 12 weeks. The primary safety endpoints were the change in the mean blood pressure (BP) values, which indicated significantly reduced systolic and diastolic BP (−3.85 mmHg [95% CI −6.81, −0.88] and −0.06 mmHg [95% CI −0.81, −0.88], respectively) and pulse rate (−1.18 [95% CI −0.79, −3.15]). In addition, kidney function was improved, with a significant reduction in the urine albumin/creatinine ratio (UACR) (−1.76 mg/g [95% CI −1.07, −34.25]) and a significant increase in the estimated glomerular filtration rate (eGFR) (3.54 mL/min/1.73 m2 [95% CI 2.78, 9.87]). Furthermore, EMPA reduced aminotransferases (ALT) in a pattern (reduction in ALT > AST). The adjusted mean difference in the change in ALT was −2.36 U/L [95% CI −1.031, −3.69], while it was −1.26 U/L [95% CI −0.3811, −2.357] for AST and −1.98 U/L [95% CI −0.44, −3.49] for GGT. Moreover, in the EMPA group, serum high-density lipoprotein (HDL) significantly increased (0.29 mmol/L [95% CI 0.74, 0.15]), whereas a nonsignificant increase was seen in low-density lipoprotein (LDL) (0.01 mmol/L [95% CI 0.19, 0.18]) along with a significant reduction in plasma triglyceride (TG) levels (−0.43 mmol/L [95% CI −0.31, −1.17]). Empagliflozin once daily is an efficacious and tolerable strategy for treating Saudi patients with insufficiently controlled T2DM as an add-on to ongoing antidiabetic therapy. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to provide reference values for the percentage total weight loss during 1 year after laparoscopic sleeve gastrectomy associated with primary response in Japan. Methods: This multicenter retrospective study comprised 248 patients with severe obesity who underwent laparoscopic sleeve gastrectomy at five institutions in Japan. A percentage total weight loss < 20% at 1 year was defined as primary non-response. Parsimonious predictive models were developed based on the results of multiple regression analyses. A receiver operating characteristic curve analysis was used to assess the discriminative performance for primary non-response. Results: The median age, initial body mass index, and percentage total weight loss at 1 year were 41 years, 41.4 kg/m2, and 30.1%, respectively. There were 28 (11.3%) primary non-responders. For discriminating primary non-responders, the areas under the receiver operating characteristic curve of the parsimonious model and actual percentage of total weight loss at 3 months after laparoscopic sleeve gastrectomy were 0.846 and 0.803, respectively. Cutoffs for the predicted percentage total weight loss using the model and actual value of percentage total weight loss at 3 months attaining 80% sensitivity were 30% and 22%, and those attaining 98% specificity were 22% and 15%, respectively. Conclusions: Reference values for the percentage total weight loss at 3 months were obtained using the predictive model and actual value of percentage total weight loss at 3 months. Patients at risk for primary non-response can be determined at 3 months with these values, which can help in considering earlier interventions. [ABSTRACT FROM AUTHOR]

Dietary and physical activity interventions through smartphone healthcare applications (apps) have recently surged in popularity as effective methods for weight loss. However, the specific factors contributing to successful weight loss remain uncertain. We conducted an analysis of baseline characteristics and app usage frequencies over three months among 68 Japanese adults with overweight and obesity who were assigned to the intervention group in a previous randomized controlled trial. Logistic regression analysis revealed a negative association (OR: 0.248; p = 0.018) between having a walking habit at baseline and successful weight loss, defined as a 3% reduction in initial weight. Additionally, slower walking speeds and family medical history were identified as potential predictors of successful weight loss. These findings offer insights into the profile of individuals who achieve success in weight loss through our smartphone app, providing valuable guidance for the development of future healthcare apps.

Aims: Weight changes from a young age are known to be associated with poor life outcomes in the general population. However, little is known about the association between weight change from a young age and life expectancy in patients with chronic kidney disease (CKD)., Methods: Data of 2,806 nondialysis CKD patients who participated in the Fukuoka Kidney Disease Registry (FKR) Study, a multicenter observational study, were analyzed. The primary outcome was all-cause death, whereas the secondary outcome was cardiovascular mortality. The covariate of interest was weight change, defined as the difference between body weight at study enrollment and at 20 years old. Cox proportional-hazards models were used to estimate the risks of mortality for participants with weight changes of ≥ 5 or ＜5 kg compared with those with stable weights., Results: During the 5-year observation period, 243 participants died from all causes and 62 from cardiovascular disease. The risk of all-cause mortality in the weight-loss group was significantly higher than that in the stable-weight group (multivariable-adjusted hazard ratio, 2.11; 95% confidence interval [CI], 1.52-2.93). Conversely, the risk of cardiovascular mortality in the weight-loss group was significantly higher than that in the stable-weight group (multivariable-adjusted hazard ratio, 2.48; 95% CI, 1.32-4.64). However, no significant association was observed between weight gain and the risks of all-cause and cardiovascular mortalities., Conclusion: Weight loss from 20 years of age was found to be associated with higher risks of all-cause and cardiovascular mortalities in patients with CKD.

• The association between weight loss and subsequent functional decline is unclear. • Older individuals with ≥1 % weight loss were at risk of functional decline. • Monitoring weight change could identify older adults at risk of functional decline. The association between weight loss and subsequent functional decline is uncertain. The study aims to elucidate the association between weight loss over a year and subsequent functional decline requiring assistance in performing their activities of daily living in older individuals. The study used data from the publicly funded Long-Term Care Insurance service in Japan, which provides coverage for long-term care services for individuals unable to perform activities of daily living due to physical or cognitive impairment. The study enrolled people born in or before 1949, who underwent health checkups in both 2014 and 2015. The participants were followed from 2015 to the worsening of functional decline requiring long-term care services, death, or February 28, 2019, whichever occurred first. The risk of subsequent functional decline in each weight loss category was estimated using a Cox regression model adjusted for age, sex, baseline body mass index, smoking, and Charlson comorbidity index. We identified 67,452 eligible individuals from the database. The median follow-up period was 1,284 days. The hazard ratios (95 % confidence interval) of functional decline for -1 %, -2 %, -3 %, -4 %, and ≤-5% weight change compared to 0 % weight change were 1.17 (1.03−1.32), 1.26 (1.11−1.43), 1.29 (1.12−1.49), 1.61 (1.39−1.87), and 1.79 (1.58−1.99), respectively. Older people with weight loss of 1 % or more were at risk of functional decline. Close weight monitoring may serve as an easy and inexpensive means of identifying older individuals at risk of functional decline. [ABSTRACT FROM AUTHOR]

Objective the present study aimed to investigate the relationship between the frequency of eating together and the risk of weight loss in older adults. Methods this was a three-year follow-up prospective cohort study based on a self-reported questionnaire. We used data from the Japan Gerontological Evaluation Study (JAGES) conducted in 2016 and 2019. The participants were independent older adults aged ≥65 years in Japan. We used >5% weight loss during follow-up as the outcome variable and frequency of eating together as the explanatory variable. The relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated based on the Poisson regression model with a Huber–White sandwich estimator for standard errors, including possible confounders. Results among 56,919 participants, the mean age was 73.0 years (1SD = 5.5) at baseline, and 47.9% were male. About 15.1% (n  = 8,596) of the participants experienced >5% weight loss during follow-up. The proportion of each category of the eating together frequency was 36.6% for 'every day', 10.3% for 'several times a week', 26.8% for 'several times a month', 20.5% for 'several times a year' and 5.8% for 'seldom'. Compared to 'every day', only 'several times a year (RR = 1.07, 95% CI = 1.01–1.13)' and 'seldom (RR = 1.17, 95% CI = 1.08–1.27)' were significantly associated with the increased risk of >5% weight loss. Conclusion there is a temporal association between less frequent opportunities to eat together and the increased risk of weight loss among independent older adults. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide, including in Japan. The Japanese Society of Gastroenterology (JSGE) and the Japanese Society of Hepatology (JSH) have established the Japanese NAFLD/NASH guidelines in 2014 and revised these guidelines in 2020. As described in these guidelines, weight reduction by diet and/or exercise therapy is important for the treatment of NAFLD patients. The I148M single nucleotide polymorphism (rs738409 C > G) of PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is widely known to be associated with the occurrence and progression of NAFLD. In the Japanese, the ratio of PNPLA3 gene polymorphisms found is approximately 20%, which is higher than that found in Westerners. In addition, the ratio of lean NAFLD patients is also higher in Japan than in Western countries. Therefore, the method for lifestyle guidance for the NAFLD patients in Japan would be different from that for the people in Western countries. The problems in the treatment of NAFLD patients include alcohol consumption and sarcopenia. Therefore, guidelines that can help clinicians treat Japanese patients with NAFLD are needed. In this expert review, we summarize evidence-based interventions for lifestyle modification (diet, exercise, alcohol, and sarcopenia) for the treatment of patients with NAFLD, especially from Japan and Asian countries. [ABSTRACT FROM AUTHOR]

Background: Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the incidence of proteinuria in the general population is still unclear. Methods: The study cohort was based on a general population of 9,33,490 from 40 to 74 years of age who had undergone annual specific health checkups. The subjects who were finally included were the 2,74,598 people for whom all the data necessary for this study were available. The incidence of proteinuria in this study was defined as negative proteinuria at the primary and secondary survey years, and newly developed proteinuria during subsequent follow-up years. Results: Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI < 18.5 kg/m2) and normal weight (18.5–24.9 kg/m2) groups, the obese group (≥ 25.0 kg/m2) with rapidly decreased weight had a lower incidence compared to those with stable weight. In the obese population, a rapid decline of BMI (− 1 to − 5 kg/m2 per year) was associated with a reduced risk (hazard ratio [95% confidence interval]; 0.89 [0.80–0.98], P = 0.02) of proteinuria. Conclusions: Weight reduction can lead to a risk reduction of 11% in the incidence of proteinuria in obese Japanese adults. This is the first study to report the effects of weight reduction on the early phase of chronic kidney disease in obesity relevant to the characteristics of the Japanese general population. The present findings might have a role in renal health promotion in Japan. [ABSTRACT FROM AUTHOR]

Background: Recent studies, predominantly in Western populations, suggest that both weight loss and weight gain are associated with an increased mortality risk in old age. However, evidence of this association in older Asian populations remains sparse. This study aimed to examine the association between weight change and all-cause mortality in a nationally representative sample of community-dwelling older Japanese people.Methods: Data were obtained from the National Survey of the Japanese Elderly, which included 4869 adults aged ≥60 years. Participants were followed for up to 30 years. We considered 3 indicators of weight change according to the follow-up interval: short-term (3 years), medium-term (6-7 years), and long-term (12-13 years). Weight change was classified as loss ≥ 5%, loss 2.5%-4.9%, stable (±2.4%), gain 2.5%-4.9%, and gain ≥ 5%. Cox proportional hazards models were used to calculate the relative mortality risk of each weight change category.Results: Weight loss ≥ 5% for all intervals was associated with higher mortality than stable weight and the effects were largely similar across all 3 intervals (hazard ratio [95% confidence interval]: 1.36 [1.22-1.51] for short-term, 1.36 [1.22-1.51] for medium-term, and 1.31 [1.11-1.54] for long-term). A similar pattern of results was observed among the young-old and old-old, and among men and women. The effect of weight loss on higher mortality was greater among those with a lower body mass index at baseline.Conclusions: These findings could inform clinical and public health approaches to body-weight management aimed at improving the health and survival of older adults, particularly in Asian populations. [ABSTRACT FROM AUTHOR]

This retrospective cohort study explored the prevalence of substantial weight loss (≥10% per year) in independent older individuals in order to develop and validate a scoring system for high-risk group identification and targeted intervention against malnutrition. We used insurance claims and the Kokuho Database (KDB), a nationwide repository of Japanese-specific health checkups and health assessments for the older people. The study included 12,882 community-dwelling individuals aged 75 years and older who were self-supported in their activities of daily living in Saga Prefecture, Japan. Health evaluations and questionnaires categorized weight-loss factors into organic, physiological, psychological, and non-medical domains. The resulting scoring system (SAGA score), incorporating logistic regression models, predicted ≥ 10% annual weight-loss risk. The results revealed a 1.7% rate of annual substantial weight loss, with the SAGA score effectively stratifying the participants into low-, intermediate-, and high-risk categories. The high-risk category exhibited a weight-loss rate of 17.6%, highlighting the utility of this scoring system for targeted prevention. In conclusion, the validated SAGA score is a crucial tool for identifying individuals at high risk of significant weight loss, enabling tailored interventions and social support benefiting both older individuals and their relatives.

Introduction: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups., Methods: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves., Results: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m 2 and 4.0% decrease in the overall cohort, 0.85 kg/m 2 and 3.9% decrease in males, and 1.2 kg/m 2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m 2 , the cutoff values were 0.75 kg/m 2 and 2.7% BMI reduction., Discussion: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population., Competing Interests: TY has received honoraria from Kyowa Kirin, MSD, Astra Zeneca, Kissei Pharmaceutical, Novo nordisk pharma, Taisho Pharmaceutical, Sumitomo pharma, and Eli Lilly Japan; research funding from Nippon Boehringer Ingelheim, and Mitsubishi Tanabe Pharma, Suntory; and subsidies or donations from Ono Pharmaceutical, and Nippon Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fukuda, Okamoto, Fukaishi, Kawakami, Tanaka, Yamada and Monzen.)

The aim of this study was to investigate the effects of weight management on menstrual status in female athletes. A total of 225 collegiate athletes and 27 para-athletes who belonged to teams affiliated with the Japanese Paralympic Committee were included in this cross-sectional survey. A self-reported questionnaire (containing information on the demographic characteristics, medical history, lifestyle habits, weight management, menstruation status, physical symptoms related to menstrual cycle, and the influence of physical symptoms experienced during the luteal phase of menstruation during training or competition.) was used to assess the results. In the collegiate athletes, the rate of regular menstrual cycle was significantly lower in those with weight loss than in those without (56.7% vs. 75.0%, P <.05). Furthermore, stress fractures were found significantly more often in those with weight loss than those without (36.1% vs. 20.3%, P <.05). In the para-athletes, 46.2% of experience in weight loss had irregular menstruations (P <.01), and all of them had physical symptoms that negatively affected their training or competition (P <.05). To prevent menstrual dysfunction related to energy deficiency in female athletes with weight management, menstrual status must be considered. [ABSTRACT FROM AUTHOR]

Objectives Weight loss is a critical health issue in older adults. Oral function is essential for nutrient intake and can be restored using dental prosthetic treatments in patients with tooth loss. This study aimed to investigate the relationship between tooth loss and weight loss among the older adults and to evaluate the magnitude of its risk reduction by dental prosthetic treatment. Design Three‐year follow‐up longitudinal study based on a self‐reported questionnaire. Setting Community‐dwelling older adults in Japan. Participants Adults aged 65 and older (n = 53,690). Measurements We used >10% weight loss during follow‐up, the number of remaining teeth, and the use of dental prostheses as the outcome variable, exposure variable, and mediator, respectively. We fitted the logistic regression model including possible confounders and calculated the odds ratios (ORs) and 95% confidence intervals (95% CIs) of the controlled direct effect (CDE) at the level of use or nonuse of the dental prosthesis based on a causal mediation analysis framework. Additionally, we calculated the proportion eliminated by the dental prosthesis. Results: The mean age of participants was 72.6 years (1 SD = 5.5), and 47.4% were males. About 5.8% (n = 3132) of them experienced >10% weight loss during the follow‐up. Weight loss was observed in 6.8% of the participants with 0–19 remaining teeth and in 4.3% of them with ≥20 remaining teeth. The CDE of 0–19 remaining teeth was greater when no one used dental prosthesis (OR = 1.41; 95% CI = 1.26–1.59) compared with that when all participants used dental prosthesis (OR = 1.26; 95% CI = 1.08–1.46). This indicated that dental prosthesis decreased the risk of weight loss by 37.3%. Conclusion: Our study revealed that tooth loss increased the risk of clinically critical levels of weight loss among community‐dwelling older adults. However, this risk was reduced by dental prosthetic treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the association of the maximum lifetime body mass index (max BMI) with hemodialysis initiation and comorbidities in Japanese hemodialysis patients. Methods: In a retrospective cross-sectional study on 724 hemodialysis patients, max BMI, age at hemodialysis initiation, and comorbidities including sleep apnea syndrome, cerebro-cardiovascular diseases, and proliferative diabetic retinopathy (PDR) were analyzed. Early hemodialysis initiation was defined as age <50 years. Result: Diabetes patients showed a higher max BMI and prevalence of atherosclerotic diseases than nondiabetes patients, despite almost the same age at hemodialysis initiation. Patients with early hemodialysis initiation showed higher male ratio, prevalence of PDR, and max BMI than those with later initiation, despite almost equal prevalence of diabetes. Receiver-operating characteristic curve analysis determined a max BMI of 28.4 kg/m2 as a reliable cutoff value for predicting early hemodialysis initiation, and this parameter was identified as an independent predictor of early hemodialysis initiation using bivariate logistic regression analysis. Vitrectomy for PDR also tended to contribute independently to early hemodialysis initiation. Conclusion: A high max BMI contributed to early hemodialysis initiation independent of diabetes. Furthermore, PDR was associated with a high max BMI and early hemodialysis initiation. These results suggest that weight reduction in young chronic kidney disease patients with obesity may prevent hemodialysis and blindness. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic intragastric balloon (IGB) placement has been performed in Japan since 2004. The nationwide surveys were repeatedly carried out to confirm the effectiveness and safety of IGB in Japan. We herein present the accumulated results. Methods: Twenty‐six Japanese endoscopists personally imported products of the BioEnterics Intragastric Balloon (BIB)/Orbera system after completing the training courses in Japan. Mail surveys were posted to them every 2 years from 2010. This study included the accumulated data of the six surveys, and excluded data from non‐Japanese patients and the Orbera365 data. Results: Between 2004 and 2019, 399 obese Japanese patients underwent IGB treatment using the BIB/Orbera system. The incidence rates of early removal of IGB within 1 week and complications due to IGB were 4.8% and 6.1%, respectively. The average percent excess weight loss (%EWL) and percent total weight loss (%TWL) at IGB removal were 46.6% and 11.5%, and successful weight loss, defined as %EWL ≥ 25% or %TWL ≥ 10%, was achieved in 65.6% or 54.5% of the patients, respectively. Multivariate analyses revealed that older age and larger saline filling volume were independent predictors of successful weight loss. At 1 year after IGB removal, successful weight loss defined by the %EWL and %TWL was maintained in 44.7% and 34.1% of the patients, respectively. Conclusion: IGB therapy using the BIB/Orbera system has been safely and effectively performed in Japan. The successful weight loss may be associated with older age and larger saline filling volume. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The prevalence of obesity is rising in Japan and represents a considerable unmet medical need. The Awareness, Care and Treatment in Obesity MaNagement – International Observation (ACTION‐IO) study was designed to identify the perceptions, attitudes and barriers to obesity care among people with obesity (PwO) and healthcare professionals (HCPs) in Japan. Materials and Methods: An online, cross‐sectional survey was carried out in 11 countries, including Japan. Results: The survey was completed by 2,001 PwO and 302 HCPs in Japan. Fewer PwO (58%) than HCPs (85%) perceived obesity as a chronic disease. Most PwO (81%) thought that weight loss was their own responsibility, and waited a considerable time before seeking support from their HCP (mean 6 years). Most PwO (64%) had made one or more serious weight loss attempt in the past. In contrast, a serious attempt at losing weight was reported by HCPs for just 21% of their patients. Just 24% of PwO had weight discussions with an HCP in the past 5 years; of those, 56% expressed positive feelings after such a conversation, and just 2% felt offended. Lack of patient motivation (68%) and patient disinterest (61%) were reported by HCPs as barriers to weight management conversations. A higher proportion of obesity specialists (37%) than non‐specialists (22%) thought their patients were motivated to lose weight. Conclusions: Our Japanese dataset shows a need to raise awareness of the pathophysiological basis and clinical management of obesity among PwO and HCPs. The largely positive feelings expressed by PwO after weight loss conversations should encourage HCPs to initiate earlier discussions before obesity‐related complications occur. [ABSTRACT FROM AUTHOR]

The study investigates the association between weight gain perception and weight change over time among Japanese adults. Data were from specific health checkups held in 2013, 2014, and 2015 by National Health Insurance in Fukushima Prefecture, Japan. We included 3677 participants who gained more than 3.0kg between 2013 and 2014. Weight gain perception was asked in 2014 using a questionnaire. The participants who perceived their weight gain of more than 3kg were categorized in the accurate group and those who did not were in the inaccurate group. Multiple linear regression models were used to assess associations between weight gain perception in 2014 and weight change between 2014 and 2015. The models were adjusted for gender, age, weight in 2014, regular physical exercise, daily physical activity, and medication. Results showed that the accurate group (β=0.217; 95% confidence interval=0.037, 0.397; P=0.018) had significantly less weight loss than those in the inaccurate group. We concluded that accurate weight gain perception was associated with an increased risk of future weight gain among Japanese adults. [ABSTRACT FROM AUTHOR]

Objectives. A single-arm prospective study was conducted among Japanese patients with type 2 diabetes having preserved ejection fraction. The aim was to investigate (1) whether liraglutide therapy could improve B-type natriuretic peptide (BNP) levels and diastolic cardiac function assessed by the E -wave to E ′ ratio (E / E ′ ) using transthoracic echocardiography (TTE), and (2) whether E / E ′ contributed to BNP improvement independent of bodyweight reduction (UMIN000005565). Methods. Patients with type 2 diabetes and left ventricular ejection fraction LVEF ≥ 40 % without heart failure symptoms were enrolled, and daily injection with liraglutide (0.9 mg) was introduced. Cardiac functions were assessed by TTE before and after 26 weeks of liraglutide treatment. Diastolic cardiac function was defined as septal E / E ′ ≥ 13.0. Results. Thirty-one patients were analyzed. BNP and E / E ′ improved, with BNP levels declining from 36.8 ± 30.5 pg / mL to 26.3 ± 25.9 pg / mL (p = 0.0014) and E / E ′ dropping from 12.7 ± 4.7 to 11.0 ± 3.3 (p = 0.0376). The LVEF showed no significant changes. E / E ′ improved only in patients with E / E ′ ≥ 13.0. Favorable changes in E / E ′ were canceled when adjusted for body mass index (BMI). Multivariate linear regression analysis revealed that the left ventricular diastolic diameter and ∆ E / E ′ /∆BMI contributed to ∆BNP/baseline BNP (p = 0.0075 , R 2 = 0.49264). Conclusions. Liraglutide had favorable effects on BNP and E / E ′ but not on LVEF. E / E ′ improvement was only seen in patients with diastolic cardiac function. Body weight reduction affected the change of E / E ′ . The BMI-adjusted E / E ′ significantly contributed to the relative change of BNP. GLP-1 analog treatment could be considered a therapeutic option against diabetic diastolic cardiac dysfunction regardless of body weight. This trial is registered with the University Hospital Medical Information Network in Japan, with clinical trial registration number: UMIN000005565. [ABSTRACT FROM AUTHOR]

Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved glycaemic status in obese and diabetic subjects. In contrast, the diets of populations with long and healthy lifespans (e.g. traditional Okinawans from Japan) are high in carbohydrate and low in protein, and several clinical and preclinical studies have linked low-carbohydrate–high-protein diets with increased mortality risk. In this paper we attempt to reconcile these contradictory findings by moving beyond traditional single-nutrient analyses to consider the interactions between nutrients on health outcomes. We do so using the Geometric Framework (GF), a nutritional modelling platform that explicitly considers the main and interactive effects of multiple nutrients on phenotypic characteristics. Analysis of human data by GF shows that weight loss and improved cardio-metabolic outcomes under carbohydrate restriction derive at least in part from reduced caloric intake due to the concomitantly increased proportion of protein in the diet. This is because, as in many animals, a specific appetite for protein is a major driver of food intake in humans. Conversely, dilution of protein in the diet leverages excess food intake through compensatory feeding for protein ('protein leverage'). When protein is diluted in the diet by readily digestible carbohydrates and fats, as is the case in modern ultra-processed foods, protein leverage results in excess calorie intake, leading to rising levels of obesity and metabolic disease. However, when protein is diluted in the diet by increased quantities of less readily digestible forms of carbohydrate and fibre, energy balance is maintained and health benefits accrue, especially during middle age and early late-life. We argue that other controversies in carbohydrate research can be resolved using the GF methodology in dietary studies. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery is effective for the treatment of patients with morbid obesity and type 2 diabetes mellitus (T2DM), for body weight loss and glycemic control. However, in Japan, there has been no previous report of the effectiveness bariatric surgery in a case of morbid obesity associated with acute onset type 1 diabetes mellitus (T1DM), in which pancreatic β-cells were destroyed and endogenous insulin was depleted. Case presentation: A 36-year-old woman with morbid obesity and T1DM, diagnosed when she was 6 years, was admitted for bariatric surgery. At her first consultation, she had a body weight of 106.7 kg and a body mass index of 42.2 kg/m2. Her HbA1c level was 9.0%, with a required daily insulin dose of 75 units. She underwent laparoscopic sleeve gastrectomy. At 1 year after surgery, her body weight had decreased to 81.0 kg and her body mass index to 32.2 kg/m2. In addition, her daily required dose of insulin had decreased to 24 units, with an improvement in her HbA1c level to 7.7%. Conclusions: Although further evidence needs to be accumulated, including long-term outcomes, laparoscopic sleeve gastrectomy may provide an effective treatment for patients with morbid obesity and T1DM for body weight loss, improvement in HbA1c level, and insulin dose reduction. [ABSTRACT FROM AUTHOR]

To identify those who might benefit from weight reduction within a large population of obese individuals, Japan Society for the Study of Obesity (JASSO) advocated the concept of "obesity disease." Here we summarize the definition, criteria, and core concepts for the management of obesity disease based on JASSO's latest guideline. JASSO defines obesity as excessive fat storage in adipose tissue associated with a BMI of ≥25 kg/m 2 . The threshold BMI of obesity is low as compared to Western countries given that Japanese individuals tend to develop obesity-related health disorders at lower BMI. Obesity with a BMI of ≥35 kg/m 2 is referred to as "high-degree obesity" as treatment strategies vary based on the degree of obesity. Obesity is diagnosed as "obesity disease" if accompanied by any of the 11 specific obesity-related health disorders that weight reduction can prevent or alleviate, or if it meets the criteria for visceral fat obesity with a visceral fat area of ≥100 cm 2 . The initial weight reduction goals for high-degree obesity disease range from 5% to 10% of their current body weight, depending on the associated health disorders. That for those with obesity disease who do not qualify as high-degree is 3% or more. If these initial goals are not achieved, intensifying dietary therapy or introducing drug therapy (or both) may be necessary. While surgical treatment is primarily indicated for high-degree obesity disease, it might be appropriate for cases of obesity disease with a BMI <35 kg/m 2 , depending on the accompanying health disorders. Enhancing the quality of life for individuals with obesity or obesity disease necessitates a broader societal approach, emphasizing the resolution of related stigma.