Junya Hironaka

Aims: To investigate the long‐term renal effects of tofogliflozin, with the shortest half‐life among sodium–glucose cotransporter 2 inhibitors, in real‐world clinical practice. Materials and methods: We retrospectively enrolled patients with type 2 diabetes mellitus treated at three affiliated hospitals between January 2015 and May 2024. The primary outcome was the change in estimated glomerular filtration rate from baseline to 72 months. After inverse probability of treatment weighting, linear mixed‐effects models were used to compare estimated glomerular filtration rate changes between the tofogliflozin and non‐tofogliflozin groups. As a sensitivity analysis, multiple imputation was performed to address missing baseline urinary albumin‐to‐creatinine ratio data. Secondary outcomes included estimated glomerular filtration rate slopes, changes in glycated hemoglobin and body weight at 72 months, and changes in urinary albumin‐to‐creatinine ratio at 48 months. Results: Among 598 participants (tofogliflozin, n = 245; non‐tofogliflozin, n = 353), estimated glomerular filtration rate decline was significantly slower in the tofogliflozin group than in the non‐tofogliflozin group ( P < 0.001). At 72 months, the least squares mean estimated glomerular filtration rate change was −4.51 and −10.64 mL/min/1.73 m ² , respectively (between‐group difference: 6.14 mL/min/1.73 m ² ). Significant between‐group differences were observed in estimated glomerular filtration rate slope, glycated hemoglobin, and body weight, but not in urinary albumin‐to‐creatinine ratio. Renal findings were consistent in the multiple imputation sensitivity analysis. Conclusions: Real‐world clinical data over 72 months suggested that tofogliflozin may slow estimated glomerular filtration rate decline.

Introduction: Diabetes mellitus is involved in the development of various diseases, including microvascular and macrovascular complications, infections, osteoporosis and dementia. This study aimed to evaluate the mediating role of obesity or metabolic abnormalities (hypertension, dyslipidaemia) in causal pathways between dietary habits (fast eating, skipping breakfast) and developing type 2 diabetes. Research design and methods: A retrospective cohort study was conducted using health examination data from employees of Panasonic Corporation in Japan. Information on participants’ dietary habits, metabolic factors and the onset of diabetes was collected. Cox regression-based causal mediation analyses were performed to assess associations among dietary habits, metabolic factors and diabetes development. Results: Among 155 963 participants, fast eating (HR 1.93, 95% CI 1.73 to 2.14) and skipping breakfast (HR 1.31, 95% CI 1.24 to 1.37) were associated with increased onset of type 2 diabetes within 13 years. Fast eating showed a strong association with diabetes risk mediated through body mass index (BMI) (proportion mediated 0.73, 95% CI 0.65 to 0.85) while skipping breakfast showed a direct association with diabetes risk not mediated through BMI (proportion mediated 0.10, 95% CI 0.07 to 0.14). Both dietary habits exhibited small mediating effects through hypertension or dyslipidaemia. Conclusions: Fast eating increases diabetes risk, primarily through BMI, whereas skipping breakfast poses a risk not through BMI. These findings suggest a mechanism by which dietary habits affect glucose metabolism.

Objective: This study investigated how changes in metabolic phenotype, defined by obesity and metabolic health, impact chronic kidney disease (CKD) development in a large cohort.Methods: A retrospective cohort study analyzed health data collected between 2011 and 2021 from 84,729 Panasonic Holdings Corporation (formerly Panasonic Corporation) employees aged ≥40 years. Metabolic phenotypes were classified as metabolically healthy with no obesity (MHNO), metabolically healthy with obesity (MHO), metabolic abnormalities with no obesity (MANO), and metabolic abnormalities with obesity (MAO). Changes in metabolic phenotype over 3 years and their association with CKD development were assessed using Cox proportional hazards models adjusted for confounding variables.Results: During a mean follow‐up of 5.1 years, a total of 12,172 of participants (14.4%) developed CKD. Transitioning from MHO to MHNO and from MAO to MANO did not reduce CKD risk compared to each stable group. In contrast, participants in the MANO‐to‐MHNO and MAO‐to‐MHO groups significantly lowered CKD risk relative to each stable group, with hazard ratios of 0.86 (95% CI: 0.77–0.96) and 0.83 (95% CI: 0.67–1.02), respectively. The same results were observed when a rapid decline in renal function was used as the outcome.Conclusions: The improvement of metabolic profile might outweigh weight reduction in CKD risk.

Background To effectively manage the progression of diabetic kidney disease, it is essential to address the associated hyperkalaemia while concurrently using renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists. In this study, we aim to evaluate the effects of administering sodium zirconium cyclosilicate (SZC) to patients with type 2 diabetes mellitus (T2DM) complicated by hyperkalaemia. Methods and analysis A total of 80 patients with type 2 diabetes and hyperkalaemia will be included in the study and randomly stratified into two groups. After consent, both groups will enter an initiation phase, receiving 10 g of SZC, three times per day for 2 days. SZC administration (5 g once daily) will subsequently commence in group A, while dietary therapy will be initiated in group B by implementing a potassium-restricted diet. The primary endpoint of the study is the proportion of normokalaemic (3.5 mEq/L≤serum potassium (sK)Ethics and dissemination Written informed consent will be obtained from all participants prior to commencing the study. This study has been approved by the Kyoto Prefectural University of Medicine Clinical Research Review Board. All data obtained from this study will be published in a peer-reviewed journal. Trial registration number jRCTs051230067.

Background: This study aimed to investigate the effects of oral semaglutide on the changes in food preference of Japanese patients with type 2 diabetes. Methods: This retrospective multicenter study included 75 patients with type 2 diabetes who received oral semaglutide. The primary outcome was the change in the score of brief-type self-administered diet history questionnaire (BDHQ) score 3 months after the initiation of oral semaglutide treatment. The secondary outcome was the change in the Control of Eating Questionnaire (CoEQ), HbA1c, and body mass index (BMI) after 3 months. Results: The median age, BMI, and HbA1c of the 23 participants were 64.0 years, 26.9 kg/m², and 7.6% (59 mmol/mol). The BDHQ results showed total energy was significantly reduced. Among the individual nutrients, carbohydrates most decreased. The CoEQ results particularly showed declines in cravings for something sweet, chocolate or chocolate flavored foods, and starchy foods, satisfaction at meals, frequency and intensity of food craving, difficulty of resisting the craving for food, and frequency of eating in response to cravings for food were significantly lower after 3 months. The mean HbA1c and BMI significantly decreased. Conclusions: In Japanese patients with type 2 diabetes, oral semaglutide treatment decreased total energy intake and changed food preferences.

Bilirubin is associated with vascular complications in diabetes. However, the correlation between bilirubin and sarcopenia or muscle strength has not been investigated. This study aimed to investigate the association between total bilirubin and skeletal muscle mass index (SMI), hand grip strength (HGS), and sarcopenia in patients with type 2 diabetes. This cross-sectional study included 1,108 patients with type 2 diabetes from three hospitals in Japan. Multiple and logistic regression analyses were used to examine the relationships between total bilirubin and SMI, HGS, and sarcopenia. Of the participants, 473 (43%) were women. The median (interquartile range) age, and glycated hemoglobin were 67 (59–73) years, and 7.4 (6.7–8.6) %, respectively. The median SMIs for women and men were 6.32 (5.73–7.04) kg/m2 and 7.53 (7.02–8.19) kg/m2, respectively. The median HGS for women and men were 21.5 (17.5–25.0) kg and 36.0 (30.0–41.5) kg, respectively. Sarcopenia was present in 11% and 12% of women and men, respectively. No correlation was observed between total bilirubin and SMI in both sexes. No significant association was observed between total bilirubin and HGS in men, whereas a positive correlation was observed in women (β = 0.18, p = 0.01). Total bilirubin was negatively associated with sarcopenia in women (odds ratio = 0.80, 95% confidence interval: 0.64–0.98, interaction p = 0.02). The total bilirubin was significantly associated with HGS and sarcopenia in women with type 2 diabetes. Total bilirubin may serve as a useful indicator of sarcopenia in Japanese women.

Aims: Despite the reported success of low‐carbohydrate diets in improving glycemic control in the Western countries, no studies have investigated the effects of such diets in Asians. We aimed to conduct a systematic review and meta‐analysis of randomized controlled trials to examine the effects of low‐carbohydrate diets on glycemic control in East Asian adults.Materials and Methods: We systematically searched the PubMed, Cochrane Library, and Embase databases from inception to June 28, 2023, to identify randomized controlled trials examining the efficacy of low‐carbohydrate diets in patients with type 2 diabetes (PROSPERO number CRD 42023453007). The primary outcome was the difference in glycated hemoglobin levels between the low‐carbohydrate diet and control groups. The secondary outcome was the difference in body mass index, fasting blood glucose level, blood pressure, and lipid profile.Results: Six randomized controlled trials met the eligibility criteria. The study duration ranged from 3 to 18 months, with five studies conducted within 6 months. The results showed that low‐carbohydrate diets were more beneficial in lowering glycated hemoglobin levels and body mass index than control diets. The risk of bias for the six studies was minimal for two and moderate for four. The heterogeneity among the studies was low.Conclusions: Low‐carbohydrate diets improved glycated hemoglobin levels and body mass index in East Asians compared with control diets. Therefore, carbohydrate restriction may be effective for glycemic management in East Asians with type 2 diabetes for at least 6 months.

Aims/Introduction: Efficacy of long‐term low‐carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long‐term LCD and glycemic control in individuals with type 2 diabetes.Materials and Methods: We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long‐term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglyceride, and weight between long‐term LCD and control groups.Results: Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long‐term LCD and control diets (standardized mean difference −0.11, 95% confidence interval −0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low‐density lipoprotein cholesterol between long‐term LCD and control diets. However, long‐term LCD were associated with greater elevation in high‐density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04–0.41; P = 0.02) and decrease in triglyceride (standardized mean difference −0.19; 95% confidence interval −0.37 to 0.02; P = 0.03) than that in control diets.Conclusions: Our findings suggest efficacy of long‐term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long‐term LCD for glycemic control in the individuals.

Aims: To assess the impact of ‘Oishi Kenko’, a nutrition management application (app), on glycaemic control in patients with diabetes. Materials and Methods: A propensity‐score‐matched retrospective cohort study was performed using data from the KAMOGAWA‐DM cohort study conducted between January and June 2022 in Japan. We analysed data from patients with type 1 and type 2 diabetes, comparing users who used the Oishi Kenko app (app group) with non‐users (control group) over 3 months. Results: Among the 50 participants who actively used it, 47 participants in both the app and control cohorts were selected from the KAMOGAWA‐DM cohort according to propensity‐score matching. Within the app group, the median glycated haemoglobin (HbA1c) level was 51 mmol/mol (6.9%) at baseline, which slightly decreased to 50 mmol/mol (6.8%) at the 3‐month mark (median change 0.0%). Conversely, in the control group, the baseline HbA1c level of 51 mmol/mol (6.9%) exhibited a marginal increase of 52 mmol/mol (7.0%) after 3 months (median change 0.20%). The median HbA1c level change between the groups was statistically significant, with the app group showing a significant positive change compared with the control group ( p = 0.012). Conclusion: The Oishi Kenko app effectively improved glycaemic control in patients with diabetes; hence, it may be a promising tool for patient‐driven dietary management.