Journal of Diabetes Investigation最新文献

{"title":"Selecting between pharmacotherapy and bariatric surgery in East Asia","authors":"Yamato Keidai, Junji Fujikura, Hiroto Minamino, Kohei Takesue, Daisuke Yabe","doi":"10.1111/jdi.70428","DOIUrl":"10.1111/jdi.70428","url":null,"abstract":"<p>The emergence of highly effective incretin-based therapies has transformed the treatment landscape for obesity, raising an increasingly important clinical question: which patients should receive pharmacotherapy, and which should undergo metabolic and bariatric surgery (MBS)? Although therapeutic options have expanded substantially, direct comparisons within comparable patient populations remain limited. Leslie <i>et al</i>.<span><sup>1</sup></span> addressed this question by comparing semaglutide, tirzepatide, and sleeve gastrectomy in a large real-world cohort of adults with type 2 diabetes and a body mass index (BMI) of at least 35 kg/m<sup>2</sup>. At 1 year, the adjusted probabilities of achieving the primary composite outcome of ≥20% weight loss and an HbA1c level below 5.7% were 3.0%, 13.2%, and 24.0% with semaglutide, tirzepatide, and sleeve gastrectomy, respectively<span><sup>1</sup></span>. This study provides an important foundation for reconsidering how obesity treatments should be compared and selected in contemporary clinical practice.</p><p>These findings should not be interpreted as establishing a universal hierarchy of obesity treatments. Treatment assignment was not randomized, and patients who underwent surgery were younger, had a higher BMI, and had a lower baseline HbA1c level than those receiving pharmacotherapy. Moreover, when the weight-loss threshold was lowered from 20% to 10%, the relative ranking of tirzepatide and surgery for the composite outcome was reversed. These observations illustrate that the relative effectiveness of obesity treatments depends both on patient characteristics and the outcomes used to define treatment success. This perspective is particularly relevant to East Asia, where differences in obesity phenotype and clinical priorities may influence how pharmacotherapy and MBS should be compared and selected.</p><p>The relationship between BMI and obesity-related disease differs substantially between East Asian and European-ancestry populations. At the same BMI, East Asians generally exhibit greater visceral and ectopic fat accumulation than individuals of European ancestry<span><sup>2</sup></span>. Consequently, applying the same BMI threshold may identify patient populations with distinct patterns of body-fat distribution, metabolic risk, and obesity-related complications. Accordingly, patients who meet the same BMI criterion may represent biologically distinct obesity phenotypes, underscoring the need for caution when extrapolating comparative treatment data across populations.</p><p>Direct comparisons of fat distribution and body composition between East Asian and European-ancestry populations are limited among individuals with severe obesity, such as those included in the study by Leslie <i>et al</i>.<span><sup>1</sup></span> (mean BMI, 43.0–47.6 kg/m<sup>2</sup>). Nevertheless, potential differences in obesity phenotype should be considered when extrapolating. Even when similar weight loss is ach","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1662-1666"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liraglutide reprograms vascular smooth muscle cell metabolism to suppress extracellular matrix remodeling in diabetic atherosclerosis","authors":"Kun Zhu,&nbsp;Hanxiu Liu,&nbsp;Ni He,&nbsp;Haoyang Wang,&nbsp;Jing Liu,&nbsp;Qinhu Zhang,&nbsp;Zhongwei Liu","doi":"10.1111/jdi.70398","DOIUrl":"10.1111/jdi.70398","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic reprogramming contributes to vascular dysfunction in diabetic atherosclerosis, but the mechanisms linking hyperglycemia-induced metabolic alterations to extracellular matrix remodeling in vascular smooth muscle cells remain incompletely understood. This study investigated whether liraglutide modulates vascular smooth muscle cell metabolism and plaque remodeling under diabetic conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Primary vascular smooth muscle cells were exposed to normal glucose, high glucose, or high glucose plus liraglutide. Cellular bioenergetics, mitochondrial function, oxidative stress, extracellular matrix remodeling, and AMPK/PGC-1α, mTOR, and HIF-1α signaling were assessed. In <i>vivo</i>, diabetic ApoE^−/− mice were treated with liraglutide for 12 weeks, followed by evaluation of metabolic parameters, aortic root plaque burden, lipid deposition, collagen content, and plaque-associated signaling markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High glucose impaired mitochondrial respiration, enhanced glycolysis, reduced mitochondrial membrane potential, increased mitochondrial reactive oxygen species, and promoted mitochondrial fragmentation and extracellular matrix remodeling in vascular smooth muscle cells. Liraglutide restored mitochondrial function, activated AMPK/PGC-1α signaling, suppressed mTOR activation and HIF-1α accumulation, reduced collagen I, MMP-2, and MMP-9 expression, and partially restored elastin levels. In diabetic ApoE^−/− mice, liraglutide improved systemic metabolic parameters, reduced atherosclerotic plaque burden and lipid accumulation, increased plaque collagen content, restored plaque p-AMPK expression, and reduced HIF-1α and MMP-9 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Liraglutide attenuates hyperglycemia-induced metabolic reprogramming and extracellular matrix remodeling in vascular smooth muscle cells and improves plaque stability in diabetic atherosclerosis. These effects are associated with restoration of AMPK/PGC-1α signaling, inhibition of mTOR activation, suppression of HIF-1α accumulation, and improved mitochondrial homeostasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1695-1707"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and psychological effects of the JADEC Diabetes Card System assessed using the Problem Areas in Diabetes (PAID): A retrospective observational study","authors":"Yu Kouchi","doi":"10.1111/jdi.70404","DOIUrl":"10.1111/jdi.70404","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Diabetes self-management education and support (DSMES) is essential for long-term diabetes care; however, its psychological impact in routine outpatient practice remains unclear. This study evaluated the clinical and psychological effects of DSMES using the Diabetes Card System, a visually structured educational tool developed in Japan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective observational study included 141 patients with type 2 diabetes who received DSMES using the Diabetes Card System at a single outpatient clinic between April 2022 and July 2025. Changes in Problem Areas in Diabetes (PAID) scores and glycated hemoglobin (HbA1c) over 6 months were analyzed. Multivariable linear regression analyses were performed to identify factors associated with changes in PAID (ΔPAID) and HbA1c (ΔHbA1c). Additional analyses were conducted according to treatment modification status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Total PAID scores and HbA1c levels significantly improved over 6 months. Baseline PAID score was the only factor associated with ΔPAID. ΔHbA1c was associated with baseline HbA1c, duration of diabetes, and age, but not with baseline PAID. Greater ΔPAID was observed in patients with higher baseline PAID scores irrespective of HbA1c levels. Treatment intensification was associated with greater reductions in HbA1c, whereas PAID improvement did not differ according to treatment modification status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DSMES using the Diabetes Card System was associated with reductions in diabetes-related distress and improvements in glycemic control in routine outpatient care. Psychological improvement appeared independent of patient background factors, whereas glycemic improvement was associated with disease-related indicators. The Diabetes Card System may represent a practical DSMES tool in routine outpatient practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1847-1855"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13417661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mediating role of genes in the influence of intestinal flora on type 2 diabetes and the screening of diagnostic markers","authors":"Yu-yang Chen,&nbsp;Yi-fan Shi,&nbsp;Xin-yue Zhang,&nbsp;Jing-yue Zhang,&nbsp;Shi-mao Zhang,&nbsp;Heng-xia Zhao,&nbsp;De-liang Liu","doi":"10.1111/jdi.70386","DOIUrl":"10.1111/jdi.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The composition of intestinal flora affects the occurrence and development of type 2 diabetes to some extent, with dysregulation of the microbiome being a clinical manifestation of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The key intestinal flora with causal relationship to type 2 diabetes was obtained by mendelian randomization (MR) analysis. Meanwhile, differentially expressed genes (DEGs) were analyzed in the GSE76894 dataset and overlapped with causal genes. The differentially expressed causal genes were screened by machine learning, and diagnostic markers of type 2 diabetes were identified. We also analyzed the expression of diagnostic markers for different cell types using the single-cell data to provide a more reliable basis for disease diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study identified 10 key intestinal flora that were causally linked to type 2 diabetes through MR analysis. Transcriptome-wide association study (TWAS) and cis-expression quantitative trait loci.(eQTL) MR analysis of type 2 diabetes identified 228 genes that were causally linked to type 2 diabetes (|Z score| &gt; 1, <i>P</i> &lt; 0.05). About 20 causal genes were selected by MR analysis of 228 genes and intestinal flora causally related to type 2 diabetes. The diagnostic markers screened by machine learning were verified by the area under the curve (AUC), the results were all &gt;0.7, indicating good diagnostic efficiency. Single-cell analysis suggested that BEND7 was specifically high expression in the control group, and C1orf85 was specifically high expression in samples with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study provided a solid theoretical basis for further understanding of the underlying mechanisms of type 2 diabetes pathogenesis and progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1816-1834"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging gaps in diabetic neuropathy care: A Delphi-based regional consensus from the Gulf Cooperation Council","authors":"Abdulrahman Alshaikh,&nbsp;Abdulnabi T Alattar,&nbsp;Ahmed Abdul Karim Hassoun,&nbsp;Afaf Alshammary,&nbsp;Hussein Elbadawi,&nbsp;Khaled Aldossari,&nbsp;Noor Al Busaidi,&nbsp;Saud Alsifri,&nbsp;Talal Muzaffar,&nbsp;Wiam I. Hussein,&nbsp;Christine Talaat,&nbsp;Abanoub Effat,&nbsp;Marwa Elsaghier,&nbsp;Rayaz A Malik","doi":"10.1111/jdi.70411","DOIUrl":"10.1111/jdi.70411","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in the Gulf Cooperation Council (GCC) region, associated with delayed diagnosis, significant pain burden, and preventable complications. This Delphi-based consensus aimed to identify regional gaps in screening and management to develop practical, evidence-based recommendations tailored to GCC healthcare systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A three-round Delphi process was conducted involving 12 diabetes experts from six GCC countries, who reviewed international guidelines, identified unmet clinical needs, and voted on consensus statements addressing epidemiology, screening, diagnosis, and treatment, with consensus defined as ≥75% agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The panel reached strong agreement on shifting from symptom-driven to proactive care, recommending routine annual screening for all individuals with diabetes and prediabetes. Experts also emphasized early, integrated management combining lifestyle modification, cardiovascular risk reduction, pathogenetic therapies, and individualized pharmacologic treatment of neuropathic pain. Key barriers identified included limited consultation time, high clinical workload, suboptimal awareness of DPN among clinicians and patients, and restricted access to guideline-recommended therapies due to regulatory constraints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This regional consensus highlights the need for standardized, proactive care of patients with DPN, across the GCC. Implementation of systematic screening, early multimodal management, and policy-level improvements in access to therapies may improve patients' quality of life and reduce complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1643-1657"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of subgingival microbiome in patients with type 2 diabetes induced by diabetes treatment","authors":"Moe Inoue,&nbsp;Akito Sakanaka,&nbsp;Naoto Katakami,&nbsp;Hitoshi Nishizawa,&nbsp;Kazuo Omori,&nbsp;Naohiro Taya,&nbsp;Asuka Ishikawa,&nbsp;Shota Mayumi,&nbsp;Hiroki Takeuchi,&nbsp;Atsuo Amano,&nbsp;Toru Takeshita,&nbsp;Eiichiro Fukusaki,&nbsp;Iichiro Shimomura,&nbsp;Masae Kuboniwa","doi":"10.1111/jdi.70408","DOIUrl":"10.1111/jdi.70408","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Diabetes and periodontal disease, a bacterial infection involving the oral microbiome, have a bidirectional relationship. However, the relationship between poor glycemic control and the oral microbiome remains unclear. The aim of this study was to assess the direct effect of intensive glycemic control on the oral microbiome in patients with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Twenty-nine patients with T2DM and 29 controls were enrolled in this study. Patients underwent a 2-week intensive glycemic control regimen. We collected subgingival dental plaque and conducted full-length 16S ribosomal RNA gene sequencing to identify bacterial species. The focus was on the subgingival microbiome, particularly 29 species of oral bacteria related to periodontal disease, and the characteristics of the diabetic cohort. Periodontal inflammation was quantified using the periodontal inflamed surface area (PISA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prior to diabetes treatment, the relative abundance of <i>Porphyromonas gingivalis</i> (<i>P</i> = 0.018), <i>Tannerella forsythia</i> (<i>P</i> &lt; 0.001), <i>Fusobacterium nucleatum</i> (<i>P</i> = 0.041), and <i>Prevotella intermedia</i> (<i>P</i> &lt; 0.001), known for their high pathogenicity in periodontal disease, was higher in the diabetes group than in the control group. The bacterial species whose relative abundance changed significantly before and after treatment differed between the PISA improved and non-improved groups in patients with diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Oral bacteria changed pre- and post-diabetes treatment, correlating with improvements in PISA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1835-1846"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of age, sex, and renal function on bowel movement-improving effects of Bifidobacterium bifidum G9-1 on constipation in patients with type 2 diabetes mellitus and chronic kidney disease: A prespecified subgroup analysis of the BIRDIE study","authors":"Fuki Ikeda,&nbsp;Junko Sato,&nbsp;Hidenori Yoshii,&nbsp;Hiroaki Satoh,&nbsp;Hirotsugu Uzawa,&nbsp;Daisuke Sugimoto,&nbsp;Reina Muto,&nbsp;Yuya Nishida,&nbsp;Hirotaka Watada","doi":"10.1111/jdi.70406","DOIUrl":"10.1111/jdi.70406","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus and chronic kidney disease are associated with increasing risk of constipation. We previously reported that <i>Bifidobacterium bifidum</i> G9-1 improved stool consistency, bowel movement, and quality of life of patients with type 2 diabetes mellitus, chronic kidney disease, and constipation. However, the effect of patients' background characteristics on the efficacy of <i>B. bifidum</i> G9-1 has not yet been investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This prespecified subgroup analysis of the BIRDIE study investigated the effect of age, sex, and baseline renal function on the efficacy of <i>B. bifidum</i> G9-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The primary endpoint, the percentage of participants with normal stool consistency at week 12, significantly increased in participants aged ≥65 years, male, and those with estimated glomerular filtration rate of ≥60 mL/min/1.73 m². Regarding the secondary endpoints, although the improved variables differed according to subgroup, the constipation score on the Gastrointestinal Symptom Rating Scale and abdominal bloating among the abdominal symptoms significantly improved in most of the subgroups, except for the subgroup including only a few participants. Metformin users were more likely to experience relief from constipation, whereas insulin users were less likely to experience improvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Patients aged ≥65 years, male, and those with estimated glomerular filtration of ≥60 mL/min/1.73 m² are more likely to benefit from treatment with <i>B. bifidum</i> G9-1. These results may provide useful guidance for considering treatment options based on patients' background characteristics upon treatment of constipation in patients with type 2 diabetes mellitus and chronic kidney disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1759-1769"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison between liraglutide and dulaglutide on the incidence or progression of eye and kidney complications","authors":"Aki Katamine,&nbsp;Junko Oya,&nbsp;Yuichiro Kondo,&nbsp;Yukiko Hasegawa,&nbsp;Tomoko Nakagami","doi":"10.1111/jdi.70407","DOIUrl":"10.1111/jdi.70407","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To evaluate and compare the risk of diabetic retinopathy and kidney disease between once-daily liraglutide and once-weekly dulaglutide in Japanese participants with type 2 diabetes (T2D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A total of 341 participants newly initiated on once-daily liraglutide 0.9 mg or once-weekly dulaglutide 0.75 mg between 2015 and 2020 were included in this study. We used propensity score-based inverse probability of treatment weighting to adjust for baseline characteristics between the two groups. The participants were divided into three cohorts according to retinopathy, albuminuria, and glomerular filtration rate (GFR). The primary outcomes were the incidence or progression of diabetic retinopathy or kidney disease (albuminuria or reduced estimated GFR (eGFR) &lt;60 mL/min/1.73 m²). The incidence rate and risk of outcomes were compared between the two groups using Poisson regression and Cox proportional hazard models. [Correction added on September 7, 2026, after first online publication: The total number of participants in the Materials and Methods section has been corrected from 331 to 341.]</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over a mean follow-up of 4.4 and 3.6 years in the liraglutide and dulaglutide groups, respectively, there were no differences between the two groups in terms of the risk of incidence of retinopathy and reduced GFR (hazard ratio (HR): 0.98 [0.60–1.60] and 0.82 [0.36–1.84]). Dulaglutide showed a lower incidence or progression rate but similar risk of albuminuria compared to liraglutide (54.7 vs 25.8 per 1,000 person-years (<i>P</i> = 0.04), HR: 0.51 [0.25–1.05]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study showed that once-daily liraglutide and once-weekly dulaglutide have similar risks for retinopathy, albuminuria, and reduced GFR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1726-1734"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat shock protein 72 attenuates atherosclerosis in apolipoprotein E-deficient mice","authors":"Rintaro Yoshizumi,&nbsp;Tatsuya Kondo,&nbsp;Takuro Watanabe,&nbsp;Nobukazu Miyakawa,&nbsp;Sayaka Kitano,&nbsp;Mary Ann Suico,&nbsp;Miki Sato,&nbsp;Masaji Sakaguchi,&nbsp;Motoyuki Igata,&nbsp;Takeshi Matsumura,&nbsp;Hirofumi Kai,&nbsp;Eiichi Araki,&nbsp;Naoto Kubota","doi":"10.1111/jdi.70373","DOIUrl":"10.1111/jdi.70373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heat shock (HS) and mild electrical stimulation (MES) induce the expression of heat shock protein 72 (HSP72), which suppresses endoplasmic reticulum stress, oxidative stress, and c-Jun N-terminal kinase (JNK) activity, thereby ameliorating pathophysiologic abnormalities associated with diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to investigate whether HS + MES influences the development of atherosclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HSP72^+/+/ApoE^−/− and HSP72^−/−/ApoE^−/− mice were fed a high-fat diet and treated with either sham or HS + MES. Atherosclerotic lesion formation and oxidative stress were evaluated histologically, while HSP72 expression, macrophage markers, and proinflammatory mediators were analyzed in bone marrow-derived macrophages (BMMs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In HSP72^+/+/ApoE^−/− mice, HS + MES reduced atherosclerotic lesion size and necrotic core formation, whereas these effects were absent in HSP72^−/−/ApoE^−/− mice. Plaque immunostaining revealed significantly lower 4-hydroxynonenal and F4/80 levels in HS + MES-treated HSP72^+/+/ApoE^−/− mice. <i>In vitro</i>, HS + MES increased HSP72 mRNA in BMMs, suppressed lipopolysaccharide-induced monocyte chemotactic protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS) expression, inhibited JNK phosphorylation, and promoted macrophage polarization from M1 to M2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, these findings indicate that induction of HSP72 expression by HS + MES prevents atherogenesis independently of glucose homeostasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1686-1694"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the miR-224-5p/PTEN pathway: A previously under-characterized strategy to attenuate mesangial cell injury and predict prognosis in diabetic nephropathy","authors":"Yanxia Gao,&nbsp;Xiaohui Zhang,&nbsp;Peng Lu,&nbsp;Qiang Wang","doi":"10.1111/jdi.70401","DOIUrl":"10.1111/jdi.70401","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To ascertain the expression status and clinical performance of miR-224-5p in diabetic nephropathy (DN), alongside its molecular mechanism of regulating mesangial cell injury by targeting <i>phosphatase and tensin homolog</i> (<i>PTEN</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serum miR-224-5p and <i>PTEN</i> mRNA expression were detected in DN patients. Logistic regression was used to analyze independent risk indexes for the poor clinical outcomes in DN. Functional gain/loss and rescue experiments were performed. Target relationships were validated through dual-luciferase reporter assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum miR-224-5p expression was significantly increased in DN patients (<i>P</i> &lt; 0.001). It displayed moderate diagnostic performance for discriminating DN from T2DM (AUC = 0.796), and good predictive value (AUC = 0.833) for predicting 2-year adverse renal outcomes. MiR-224-5p level was significantly higher in patients with an unfavorable prognosis than those with a favorable prognosis (<i>P</i> &lt; 0.001). Elevated miR-224-5p was identified as an independent risk factor for eGFR decline ≥30% (<i>P</i> = 0.001), but this finding was not applicable to end-stage renal disease (ESRD) due to insufficient case numbers for multivariate analysis. MiR-224-5p inhibition protected high-glucose mesangial cells via <i>PTEN</i> upregulation, an effect reversed by si-<i>PTEN</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Increased miR-224-5p expression may serve as a potential circulating biomarker for predicting eGFR decline in DN patients, but these findings are preliminary and require validation in independent cohorts using standardized exogenous spike-in normalization before clinical application. The independence of this association was only demonstrated for the eGFR decline ≥30% endpoint and not for ESRD due to limited statistical power.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1744-1758"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}