Genetic and Clinical Characteristics of Monogenic Diabetes in Japan: A Nationwide Study by the Japan Diabetes Society.

Context: Monogenic diabetes is often underdiagnosed because of limited genetic testing opportunities and varying screening criteria.

Objective: To investigate the genetic and clinical characteristics of monogenic diabetes in Japan and assess the utility of classical screening criteria and the maturity-onset diabetes of the young (MODY) probability calculator.

Design And Setting: This study included a total of 232 probands with diabetes onset before age 35, BMI <30 kg/m², and negative islet autoantibodies, recruited from 2019 to 2024.

Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene.

Psoriasis vulgaris (PsV) is an immune-mediated inflammatory skin disorder with complex genetic architecture. Most genome-wide association studies (GWASs) of PsV have been limited to analyzing common single-nucleotide variants in Europeans, lacking diversity in the variant spectrum and ancestral background. To investigate the contribution of rare variants (RVs) and structural variants (SVs), we perform a whole-genome sequencing study involving 1,415 PsV cases and 3,968 controls in Japanese.

Impact of the COVID-19 Pandemic on Health Check-ups before and after the COVID-19 Downgrade and Employees' Mental Health at Health Check-up Facilities: The Third Nationwide Survey of Healthcare Facilities in Japan Society of Ningen Dock and Preventive Medical Care.

Introduction: Preventive programs, including cancer and diabetes screenings, were disrupted globally by the coronavirus disease 2019 (COVID-19) pandemic and had not returned to pre-pandemic levels even in 2021-2022. In Japan, COVID-19 was downgraded to the lowest-risk category under the Infectious Diseases Control Law in May 2023. However, whether participation in health check-ups recovered after this downgrade remains unclear.

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Exploratory Analysis of Serum Oxidized Albumin as a Potential Prognostic Indicator for Diabetic Microvascular Complications: A Retrospective Cohort Pilot Study.

Introduction Oxidative stress is known to play a key role in the pathogenesis of diabetic complications. However, a useful biomarker of oxidative stress has not yet been widely adopted in clinical practice. We explored whether the ratio of serum oxidized albumin (human non-mercaptalbumin, HNA) to total albumin (HNA%) is associated with the five-year prognosis of diabetic complications.

Efficacy and safety of once-weekly tirzepatide in Japanese participants with type 2 diabetes who have obesity or overweight: Subpopulation analysis of the SURMOUNT-2 trial.

Aim: To assess the efficacy and safety of once-weekly tirzepatide in Japanese participants with obesity and type 2 diabetes (T2D).

Materials And Methods: This subpopulation analysis of 41 Japanese participants from three clinical trial sites in the SURMOUNT-2 trial evaluated the efficacy and safety of tirzepatide as an adjunct to lifestyle interventions in adults with body mass index ≥27 kg/m and a diagnosis of T2D with glycated haemoglobin ≥7% to ≤10%. Coprimary endpoints were mean percent change in body weight and proportion of participants who achieved ≥5% body weight reduction at week 72.

Quantitative image analysis of nailfold capillaries during an in-hospital education program for type 2 diabetes or obesity.

Nailfold capillaries are small U-shaped vessels located beneath the skin at the proximal part of the fingernail, and their morphology changes owing to various diseases. This study quantitatively analyzed nailfold capillaries using microscopy in patients hospitalized for 2 weeks for education and treatment of type 2 diabetes (T2D) or obesity. Our results suggest that nailfold arterial diameter and smoking history are useful predictors of diabetic neuropathy.

Children Comorbidity Score, a Simple Predictor for In-hospital Mortality: A Nationwide Inpatient Database Study in Japan.

Introduction: Utilizing a nationwide inpatient database in Japan, we aimed to develop a novel comorbidity score for pediatric patients to predict in-hospital mortality-the Children Comorbidity Score (CCS)-based on the International Classification of Diseases, 10th Revision (ICD-10) codes.

Methods: We retrospectively analyzed pediatric patients hospitalized between 2010 and 2017 using the Japanese Diagnosis Procedure Combination database. Eighty percent of the data was used as a training set, where we applied Lasso regression to a model with 56 candidate comorbidity categories to predict in-hospital mortality.

Age different effects of SGLT2 inhibitors on body composition in individuals with type 2 diabetes: A retrospective cohort study.

Purpose: This study investigates the long-term impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i)on body composition in individuals with type 2 diabetes (T2D), with a focus on age-related differences. We evaluated changes in body mass index (BMI), body fat percentage, skeletal muscle mass and skeletal muscle mass index (SMI) over 4.4 years on average.

Steatotic liver index: An interpretable predictor of steatotic liver disease using machine learning with an enhanced shrinkage method.

Aim: While the Fatty Liver Index (FLI) has been the most prominent among interpretable predictors for steatotic liver disease (SLD), we aimed to prepare a novel diagnostic/prognostic index better than FLI for SLD using a non-black-box and modified parsimonious machine learning method.

Methods: We included individuals who participated in an annual health checkup in Tokyo, Japan, between January 2008 and December 2018. In the training set (randomly selected 80% of the sample), we developed a novel interpretable model, Steatotic Liver Index (SLI), using a modified method of least absolute shrinkage and selection operator regression focusing on parsimony and interpretability using as few variables as FLI, and confirming its superiority to FLI using the test set (the remaining 20%).

Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases.

Biological mechanisms underlying multimorbidity remain elusive. To dissect the polygenic heterogeneity of multimorbidity in twelve complex traits across populations, we leveraged biobank resources of genome-wide association studies (GWAS) for 232,987 East Asian individuals (the 1st and 2nd cohorts of BioBank Japan) and 751,051 European individuals (UK Biobank and FinnGen). Cross-trait analyses of respiratory and cardiometabolic diseases, rheumatoid arthritis, and smoking identified negative genetic correlations between respiratory and cardiometabolic diseases in East Asian individuals, opposite from the positive associations in European individuals.

Activin B improves glucose metabolism via induction of Fgf21 and hepatic glucagon resistance.

Orchestrated hormonal interactions in response to feeding and fasting play a pivotal role in regulating glucose homeostasis. Here, we show that in obesity, the production of follistatin-like 3 (FSTL3), an endogenous inhibitor of Activin B, in adipose tissue is increased in both mice and humans. The knockdown of FSTL3 improves insulin sensitivity and glucose tolerance in diabetic obese db/db mice.

Impact of the COVID-19 pandemic and COVID-19 downgrade on non-COVID-19 respiratory diseases in Japan.

Objectives: A worldwide decrease in the incidence of respiratory diseases during the coronavirus disease (COVID-19) pandemic has been reported, largely due to non-pharmaceutical interventions (NPIs). However, the impact of lifting NPIs remains unclear. In Japan, NPIs were lifted rather drastically when COVID-19 was downgraded on May 8, 2023.

Efficacy of a Personalized Mobile Health Intervention (BedTime) to Increase Sleep Duration Among Short-Sleeping Patients With Type 2 Diabetes: Protocol for a Pilot Randomized Controlled Trial.

Background: A strong association exists between sleep duration and glycemic control in patients with type 2 diabetes (T2D), yet convincing evidence of a causal link remains lacking. Improving sleep is increasingly emphasized in clinical T2D treatment guidance, highlighting the need for effective, scalable sleep interventions that can affordably serve large populations through mobile health (mHealth).

Objective: This study aims to pilot an intervention that extends sleep duration by modifying bedtime behavior, assessing its efficacy among short-sleeping (≤6 hours per night) patients with T2D, and establishing robust evidence that extending sleep improves glycemic control.

Effect of once-weekly subcutaneous semaglutide on abdominal visceral fat area in Japanese adults with overweight and obesity: A post hoc analysis of the STEP 6 trial.

Objective: A post hoc analysis of a subset of participants with visceral fat area (VFA) measurements in the STEP 6 trial was conducted to examine both the correlation between VFA and clinical parameters and the effect of semaglutide on VFA in key subgroups.

Methods: Participants were Japanese adults aged ≥ 20 years with obesity disease, randomized to once-weekly subcutaneous semaglutide 2.4 mg, semaglutide 1.

LGR signaling and metabolic regulation: A new frontier in addressing insulin resistance and diabetes treatment.

LGR signaling plays a crucial role in metabolic regulation by coordinating muscle-neuron-adipose tissue crosstalk. In response to a high-sugar diet, muscle-derived BMP signaling activates neuronal Bursicon, which stimulates insulin secretion and enhances adipose insulin sensitivity. This evolutionarily conserved pathway underscores LGR4 as a promising therapeutic target for insulin resistance and diabetes.

Personalized mHealth Intervention (StepAdd) for Increasing Physical Activity in Japanese Patients With Type 2 Diabetes: Secondary Analysis of Social Cognitive Theory Measurements of a Single-Arm Pilot Study.

Background: A 12-week pilot of the StepAdd mobile health (mHealth) behavior change intervention based on social cognitive theory (SCT) saw an 86.7% increase in mean daily step counts among patients with type 2 diabetes. Due to the lack of exploration of theoretical implications in mHealth intervention studies, there is a need to understand the mechanism underlying the behavioral change to inform the future design of digital therapeutics.

Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1).

Aims/introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT).

Temporal trends in time toxicity of R-CHOP: a nationwide hospital-based database analysis in Japan.

Purpose: While the prognosis of patients with cancer has improved, the time burden of treatment has recently been recognized as time toxicity; although, the actual clinical situation remains largely unexplored. This retrospective study aimed to elucidate the time toxicity of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with B-cell lymphoma and the factors influencing it.

Methods: We used a nationwide hospital-based database between January 2010 and November 2021 in Japan.

Correction: Glycemic Control, Renal Progression, and Use of Telemedicine Phone Consultations Among Japanese Patients With Type 2 Diabetes Mellitus During the COVID-19 Pandemic: Retrospective Cohort Study.

[This corrects the article DOI: 10.2196/42607.].

Development of computer adaptive tests to assess the psychological status of individuals with an eating disorder or type 2 diabetes.

Background: Individuals with type 2 diabetes and eating disorders must change their eating behaviors, which are often influenced by psychological factors like depression and anxiety. To efficiently assess daily psychological status, the present study aimed to develop computerized adaptive tests (CAT) based on item response theory (IRT).

Methods: Individuals with depression, anxiety disorders, eating disorders, type 2 diabetes, and healthy persons participated in the study.

Recognition of ophthalmology consultation and fundus examination among individuals with diabetes in Japan: A cross-sectional study using claims-questionnaire linked data.

Aims: This study aimed to assess the relationship between individuals' recognition of ophthalmology consultation recommendations, their knowledge of the recommended frequency of diabetic retinopathy screening, and the likelihood of undergoing fundus examinations.

Materials And Methods: This cross-sectional secondary analysis linked claims and health checkup data to a questionnaire survey. Questionnaires were distributed to randomly sampled National Health Insurance beneficiaries in Tsukuba City, using data from claims and health checkups.

Clinical characteristics affecting weight loss in an East Asian population receiving semaglutide: A STEP 6 subgroup analysis.

Objective: To explore the effects of semaglutide versus placebo on body weight (BW) by subgroups of baseline characteristics.

Methods: In STEP 6, Japanese and Korean adults with overweight or obesity were randomized to subcutaneous semaglutide 2.4 mg, semaglutide 1.

Using One-Shot Prompting of Non-Fine-Tuned Commercial Artificial Intelligence to Assess Nutrients from Photographs of Japanese Meals.

Background: Diet interventions often have poor adherence due to burdensome food logging. Approaches using photographs assessed by artificial intelligence (AI) may make food logging easier, if they are adequately accurate.

Method: We used OpenAI's GPT-4o model with one-shot prompts and no fine-tuning to assess energy, fat, protein, carbohydrate, fiber, and salt through photographs of 22 meals, comparing assessments to weighed food records for each meal and to assessments of dieticians.