Journal of Diabetes Investigation最新文献_第3页

M1 macrophage-derived exosomes aggravate diabetic nephropathy by regulating the WTAP/S1PR2 axis. M1巨噬细胞来源的外泌体通过调节WTAP/S1PR2轴加重糖尿病肾病。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-26 DOI: 10.1111/jdi.70446

Lei Li, Hongmei Liu, Yu Mao, Huanhuan Wang, Lige Song, Zhiqiang Kang

{"title":"M1 macrophage-derived exosomes aggravate diabetic nephropathy by regulating the WTAP/S1PR2 axis.","authors":"Lei Li, Hongmei Liu, Yu Mao, Huanhuan Wang, Lige Song, Zhiqiang Kang","doi":"10.1111/jdi.70446","DOIUrl":"10.1111/jdi.70446","url":null,"abstract":"Background: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. The specific role of M1 macrophage-derived exosomes in DN progression remains largely unexplored.Methods: THP-1 monocytes were differentiated into M0 macrophages and polarized into M1 macrophages for exosome extraction. WTAP was silenced using shRNA to generate WTAP-deficient exosomes. Glomerular endothelial cells (GECs) were exposed to high glucose (HG) and co-incubated with modified exosomes. Cell viability, oxidative stress, apoptosis, barrier function, and angiogenic capacity were assessed. The WTAP-S1PR2 interaction was validated by RIP, MeRIP, and dual-luciferase assays. In vivo, db/db mice received tail vein injections of respective exosomes for 8 weeks, followed by assessments of renal function, histopathology, and inflammation.Results: M1 exosomes were internalized by GECs. WTAP delivered by shNC/M1-Exo bound S1PR2 mRNA, enhancing its m6A modification and stability, thereby activating the RhoA/ROCK1 axis and aggravating HG-induced GEC injury, oxidative stress, apoptosis, and endothelial permeability. Conversely, shWTAP/M1-Exo attenuated these effects, and S1PR2 overexpression reversed the protective effects. In vivo, shWTAP/M1-Exo improved renal function, ameliorated histopathological damage and fibrosis, and reduced systemic inflammation in db/db mice.Conclusion: M1 macrophage-derived exosomes promote DN progression by delivering WTAP to stabilize S1PR2 mRNA in an m6A-dependent manner. Engineered exosomes lacking WTAP represent a promising targeted nanomedicine strategy for DN treatment.","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056662","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}

引用次数: 0

Clinical characteristics and disease progression of typical adult-onset type 1 diabetes and insulin-dependent latent autoimmune diabetes in adults. 成人发病的典型1型糖尿病和胰岛素依赖性潜伏性自身免疫性糖尿病的临床特征和疾病进展

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-25 DOI: 10.1111/jdi.70449

Chanoknan Luksameejaroenchai, Thanida Tangjarusritaratorn, Lukana Preechasuk

{"title":"Clinical characteristics and disease progression of typical adult-onset type 1 diabetes and insulin-dependent latent autoimmune diabetes in adults.","authors":"Chanoknan Luksameejaroenchai, Thanida Tangjarusritaratorn, Lukana Preechasuk","doi":"10.1111/jdi.70449","DOIUrl":"10.1111/jdi.70449","url":null,"abstract":"Aims: We investigated the characteristics of typical adult-onset type 1 diabetes (T1D) and insulin-dependent latent autoimmune diabetes in adults (LADA) in Thailand.Methods: This retrospective chart review enrolled typical T1D and insulin-dependent LADA patients diagnosed at age ≥30 years, and who were followed up at Siriraj Hospital, Thailand, during 2014-August 2024. Potential patients were searched from the Type 1 Diabetes Registry of Siriraj Diabetes Center and electronic medical record.Results: Among 84 patients, 32 were typical T1D and 52 LADA. At diagnosis, both groups had normal body mass index (20.9 ± 4.5 kg/m2), significant weight loss (13.3 ± 6.4%), short duration of hyperglycemic symptoms (1 [1-2] months), and high fasting blood glucose (259 [174-345] mg/dL). Diabetic ketoacidosis (DKA) was the first presentation in 76.7% of typical T1D and in 2.6% of LADA. Anti-glutamic acid decarboxylase (anti-GAD) was tested in 91.7% of patients (positive: T1D 72%, LADA 100%). Almost 70% of patients with LADA were initially misdiagnosed as T2D and were ultimately diagnosed at 7.6 [2.6-17.5] years later. Patients with LADA had a higher incidence of recurrent DKA. At latest follow-up, patients with LADA had significantly higher systolic blood pressure (SBP), glycated hemoglobin (HbA1c), and insulin resistance compared to typical T1D.Conclusions: We found a higher proportion of LADA than typical T1D, and 70% of LADA were initially misdiagnosed as T2D. Both groups were characterized by a normal BMI, significant weight loss, and a short duration of hyperglycemic symptoms. However, LADA rarely presented with DKA and had higher HbA1c and insulin resistance during follow-up.","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056578","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}

引用次数: 0

Linagliptin increases the expression of LRP2 independent of Nrf2 in streptozotocin-induced diabetic mice. 利格列汀增加链脲佐菌素诱导的糖尿病小鼠中不依赖Nrf2的LRP2的表达。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-25 DOI: 10.1111/jdi.70454

Suratsawadee Promsuwan, Yumi Takiyama, Takao Takiyama, Yuri Takiyama, Hiroya Kitsunai, Hiroshi Nomoto

{"title":"Linagliptin increases the expression of LRP2 independent of Nrf2 in streptozotocin-induced diabetic mice.","authors":"Suratsawadee Promsuwan, Yumi Takiyama, Takao Takiyama, Yuri Takiyama, Hiroya Kitsunai, Hiroshi Nomoto","doi":"10.1111/jdi.70454","DOIUrl":"10.1111/jdi.70454","url":null,"abstract":"Aims/introduction: Oxidative stress is thought to play a role in the onset and progression of diabetic nephropathy (DN). Nuclear factor erythroid-related factor 2 (Nrf2) is a master regulator of antioxidant and detoxification pathways and provides cellular protection against oxidative stress. This study aimed to examine the antioxidant effects of linagliptin, a dipeptidyl peptidase-4 inhibitor, on DN using streptozotocin (STZ)-induced diabetic Nrf2 knockout (Nrf2KO) mice.Materials and methods: Six-week-old male Nrf2KO mice and their wild-type (WT) littermates were intraperitoneally injected with STZ (55 mg/kg) for five consecutive days to induce diabetes (DM) and/or treated with linagliptin (10 mg/kg/day) for 8 weeks. We also investigated the effects of linagliptin and high glucose concentrations on Nrf2-mediated signaling in human renal proximal tubular epithelial cells (HRPTECs) using a NRF2-specific siRNA.Results: Despite the lack of effect on the pathological changes and higher blood glucose levels, linagliptin reduced urinary albuminuria in diabetic mice. Interestingly, linagliptin increased the expression of NADP(H): quinone oxidoreductase-1 (NQO1) and LRP2 (megalin) in renal proximal tubular cells of WT and Nrf2KO mice, and these effects were accompanied by the activation of the AKT pathway. Linagliptin increased the expression of LRP2 under high glucose conditions through a mechanism independent of NRF2. Finally, an AKT siRNA abolished the stimulatory effects of linagliptin on LRP2 expression in HRPTECs.Conclusions: These results suggested that linagliptin reduced albuminuria in individuals with DN in an NRF2-independent manner and might exert its effects by upregulating LRP2 expression via the AKT pathway.","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056642","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}

引用次数: 0

Effect of pemafibrate on LDL-cholesterol properties in type 2 diabetes and hypertriglyceridemia by lipid management status: PARM-T2D post hoc analysis. 通过脂质管理状态对2型糖尿病和高甘油三酯血症患者低密度脂蛋白胆固醇特性的影响：PARM-T2D事后分析

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-25 DOI: 10.1111/jdi.70456

Hiroya Kitsunai, Kenichi Kito, Kazuno Omori, Kyu Yong Cho, Akinobu Nakamura, Jun Takeuchi, So Nagai, Ichiro Sakuma, Hiroshi Nomoto

{"title":"Effect of pemafibrate on LDL-cholesterol properties in type 2 diabetes and hypertriglyceridemia by lipid management status: PARM-T2D post hoc analysis.","authors":"Hiroya Kitsunai, Kenichi Kito, Kazuno Omori, Kyu Yong Cho, Akinobu Nakamura, Jun Takeuchi, So Nagai, Ichiro Sakuma, Hiroshi Nomoto","doi":"10.1111/jdi.70456","DOIUrl":"10.1111/jdi.70456","url":null,"abstract":"Although pemafibrate attracts attention for reducing LDL-C in patients with high baseline LDL-C, its comprehensive effects remain unclear in patients with type 2 diabetes. This post hoc analysis of the PARM-T2D study investigated the effects of pemafibrate on LDL-C concentration and particle size in 156 subjects with type 2 diabetes and hypertriglyceridemia, categorized by baseline LDL-C levels. While triglycerides and remnant lipoprotein cholesterol significantly improved across all groups over 52 weeks, the impact on LDL-C was multifaceted and dependent on baseline status. In participants with low baseline LDL-C, concentrations increased without a rise in ApoB, suggesting an improvement in particle size. Conversely, in those with high baseline LDL-C, both LDL-C and ApoB decreased, reflecting favorable modifications according to baseline LDL-C control status. These findings suggest that pemafibrate exerts beneficial, status-dependent effects on LDL-C properties, potentially reducing cardiovascular risk by improving LDL particle quality and quantity in high-risk patients with diabetes.","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035675","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}

引用次数: 0

Giant abdominal hematoma from injection into an insulin ball during dual antithrombotic and corticosteroid therapy. 双重抗血栓和皮质类固醇治疗期间注射胰岛素球引起的巨大腹部血肿。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-24 DOI: 10.1111/jdi.70455

Yasuhiro Tanji, Hiroshi Komamura, Takashi Mita, Shojiro Sawada

引用次数: 0

Association of atherogenic index of plasma with gestational diabetes mellitus and birth weight outcomes, and the mediating role of blood glucose. 血浆动脉粥样硬化指数与妊娠期糖尿病和出生体重结局的关系，以及血糖的中介作用。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-24 DOI: 10.1111/jdi.70452

Doudou Zhao, Yanfang Song, Nan Li, Yu Zhang, Yiting Li, Kangxin Wang, Yang Mi, Lei Shang, Pengfei Qu

{"title":"Association of atherogenic index of plasma with gestational diabetes mellitus and birth weight outcomes, and the mediating role of blood glucose.","authors":"Doudou Zhao, Yanfang Song, Nan Li, Yu Zhang, Yiting Li, Kangxin Wang, Yang Mi, Lei Shang, Pengfei Qu","doi":"10.1111/jdi.70452","DOIUrl":"10.1111/jdi.70452","url":null,"abstract":"Aims: This study aimed to examine the associations of maternal first-trimester atherogenic index of plasma (AIP) with gestational diabetes mellitus (GDM) and birth weight outcomes, and the mediating role of second-trimester blood glucose.Methods: This prospective cohort study included 5,706 pregnant women without pre-existing diabetes or other chronic diseases. AIP was calculated as log10[TG (mg/dL)/HDL-C (mg/dL)] from fasting lipid profiles. Generalized linear models and mediation analysis were used to assess the relationships between AIP and outcomes, and the mediating effects of blood glucose.Results: Participants had a mean maternal age of 29.3 years, a mean first-trimester AIP of 0.28 ± 0.19, GDM prevalence of 20.64%, and mean neonatal birth weight of 3314.05 ± 442.11 g. A 1-unit increase in first-trimester AIP was associated with greater birth weight (β: 93.12 g, 95% CI: 39.38-146.87), elevated GDM risk (RR: 2.08, 95% CI: 1.52-2.85), and higher risk of large-for-gestational-age infants (RR: 1.67, 95% CI: 1.09-2.58). A nonlinear association was identified between first-trimester AIP and birth weight, with a 158.95 g (β: 158.95 g, 95% CI: 90.70-227.20) rise per 1-unit elevation in AIP above 0.14. Fasting plasma glucose (FPG) mediated 28.35% of the association between AIP and birth weight, rising to 60.04% among women with GDM. The third-trimester rise in AIP was significantly smaller in women with GDM.Conclusions: First-trimester AIP appears to correlate with GDM and birth weight. Second-trimester FPG mediates this association, particularly in mothers with GDM. These findings support the clinical value of early lipid monitoring in prenatal care.","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029313","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}

引用次数: 0

Glycated albumin: An old yet new biomarker in people with diabetes and the potential for novel applications. 糖化白蛋白：糖尿病患者的一种古老而又新的生物标志物及其潜在的新应用。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-24 DOI: 10.1111/jdi.70447

Masakazu Aihara, Naoto Kubota

{"title":"Glycated albumin: An old yet new biomarker in people with diabetes and the potential for novel applications.","authors":"Masakazu Aihara, Naoto Kubota","doi":"10.1111/jdi.70447","DOIUrl":"10.1111/jdi.70447","url":null,"abstract":"Glycated albumin (GA), the product of nonenzymatic glycation of serum albumin, reflects the mean glucose levels over the preceding approximately 2 weeks, bridging the gap between daily self-monitoring of blood glucose and the roughly 3-month window covered by glycated hemoglobin (HbA1c) measurement. First quantified in the early 1980s, GA was long overshadowed by HbA1c, but at present, interest has revived for two reasons. First, HbA1c assessment proves unreliable when the erythrocyte lifespan or hemoglobin glycation is perturbed, as in patients with renal failure, hemolytic anemia, hemoglobin variants, and iron deficiency. Second, continuous glucose monitoring has drawn attention to postprandial excursions and shortterm glucose variability that are not captured by HbA1c. This review revisits GA's biology, measurement, standardization, clinical utility, limitations, and evidence linking it to diabetic complications. Because it responds within 2 weeks to treatment and is markedly influenced by postprandial glucose excursions, GA supports early monitoring of therapy, and its ratio to HbA1c serves as an index of postprandial glycemia and insulin secretion. However, it must also be recognized that conditions that alter albumin turnover change GA levels independently of blood glucose levels. The prognostic value of GA is strongest in patients on maintenance hemodialysis, although recent studies in various cohorts and a meta-analysis have expanded situations in which GA measurement is of prognostic value. New measurement approaches, including finger-prick sampling, weekly home measurement, and noninvasive saliva and tear assays, point toward a renewed role for GA measurement in everyday glucose monitoring in individuals with diabetes.","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029285","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}

引用次数: 0

Comment on "Frailty and low body mass index as key determinants of sodium-glucose cotransporter 2 inhibitor-specific adverse event-related discontinuation in adults aged ≥75 years: A multicenter real-world retrospective cohort study". 评论“虚弱和低体重指数是75岁以上成人钠-葡萄糖共转运蛋白2抑制剂特异性不良事件相关停药的关键决定因素：一项多中心真实世界回顾性队列研究”。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-23 DOI: 10.1111/jdi.70444

Jinmao Dai, Xiaohu Ma, Xiao Lei

引用次数: 0

Beyond PAID ≥40: Preserving the clinical meaning of diabetes distress in type 1 diabetes. ≥40：保留1型糖尿病患者糖尿病窘迫的临床意义。

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-09-22 DOI: 10.1111/jdi.70442

Shinichiro M Koga

引用次数: 0

Beyond global diabetes distress: What does PAID capture in type 1 diabetes? 超越全球糖尿病困扰：pay在1型糖尿病中捕获了什么？