Journal of Diabetes最新文献

{"title":"Glycated Albumin-Guided Therapy: Biomarker Utility or Earlier Treatment Intensification?","authors":"Muhammet Fatih Şahin","doi":"10.1111/1753-0407.70274","DOIUrl":"https://doi.org/10.1111/1753-0407.70274","url":null,"abstract":"<p>We read with great interest the randomized controlled trial by Ren et al. evaluating glycated albumin (GA)-guided treatment in patients with newly diagnosed type 2 diabetes mellitus (T2DM) [<span>1</span>]. The authors should be commended for conducting a multicenter randomized trial addressing an important question: whether a biomarker reflecting shorter-term glycemic exposure can facilitate earlier therapeutic decisions. Nevertheless, several aspects warrant consideration when interpreting the clinical utility of the proposed GA-guided strategy.</p><p>First, the primary endpoint was unequivocally neutral. The proportion of participants achieving HbA1c <7% at 12 weeks was virtually identical between the GA-guided and standard-treatment groups (64.3% vs. 64.4%; <i>p</i> = 0.99). In contrast, much of the suggested benefit derives from secondary outcomes, including changes in HbA1c, HOMA-β, HOMA-IR, anthropometric measures, and the more stringent HbA1c target. Given the number of secondary comparisons, clarification regarding adjustment for multiplicity would be valuable, as nominally significant secondary findings should be interpreted cautiously when the prespecified primary endpoint is negative.</p><p>Second, the reported advantage for achieving HbA1c <6.5% deserves particular attention. In the full analysis set, the difference did not reach conventional statistical significance (35.7% vs. 23.8%; <i>p</i> = 0.065), whereas significance emerged in the per-protocol analysis (40.5% vs. 25.3%; <i>p</i> = 0.034). Because randomization primarily supports inference according to the intention-to-treat principle, emphasizing the per-protocol result may overstate the robustness of this secondary finding.</p><p>More importantly, the trial raises a mechanistic question: does it demonstrate the clinical value of GA itself, or the benefit of earlier treatment intensification triggered by GA? Combination therapy increased from 23.5% to 63.7% in the GA-guided group, while remaining approximately 18%–19% in the standard-treatment group [<span>1</span>]. Thus, differences in HbA1c reduction, body weight, HOMA-IR, and HOMA-β may largely reflect greater treatment intensity rather than an independent advantage conferred by GA measurement. Previous trials such as VERIFY have already demonstrated potential benefits of early combination therapy in newly diagnosed T2DM [<span>2</span>]. A design comparing GA-guided intensification with protocolized early intensification based on readily available glycemic measures could better isolate the incremental clinical value of GA.</p><p>Finally, improvements in HOMA-β and HOMA-IR over only 12 weeks should not necessarily be interpreted as evidence of durable β-cell recovery or improved insulin sensitivity. These indices may change rapidly following amelioration of glucotoxicity, weight reduction, and treatment intensification.</p><p>Ren et al. provide valuable evidence regarding the feasibility of GA-guided management. ","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Fixed-Dose Combination Metformin and Empagliflozin in Type 2 Diabetes: A Prospective, Multicenter, Real-World Study From China","authors":"Weijian Ke,&nbsp;Yinghong Kong,&nbsp;Songbo Fu,&nbsp;Liyun Wang,&nbsp;Ying Pan,&nbsp;Shao Zhong,&nbsp;Yanhua Jiang,&nbsp;Hui Chen,&nbsp;Xuehua Jiao,&nbsp;Fuxing Sha,&nbsp;Liwu Xu,&nbsp;Wei Shao,&nbsp;Fenghua Lan,&nbsp;Xiaoli Chen,&nbsp;Bo Yan,&nbsp;Guangju Zhou,&nbsp;Ping Shi,&nbsp;Fen Li,&nbsp;Huike He,&nbsp;Hong Li,&nbsp;Guangwu Zhang,&nbsp;Hongyu Duan,&nbsp;Fang Wang,&nbsp;Weikun Gong,&nbsp;Yuxiao Bai,&nbsp;Bin Wang,&nbsp;Xin Mou,&nbsp;Liying He,&nbsp;Wukun Ma,&nbsp;Junhua Song,&nbsp;Juan Zheng,&nbsp;Xiaosu Bai,&nbsp;Xiaosi Li,&nbsp;Xin Yan,&nbsp;Yanqiu Wang,&nbsp;Zhenhua Wang,&nbsp;Juan Yuan,&nbsp;Wei Lu,&nbsp;Yuan Liang,&nbsp;Yufan Wang,&nbsp;Fenjuan Xu,&nbsp;Xuefeng Li,&nbsp;Xuan Lin,&nbsp;Hongbin Zhu,&nbsp;Lingling Xu,&nbsp;Xiaojia Lou,&nbsp;Lingxiao Wang,&nbsp;Lijuan Cui,&nbsp;Lijun Wang,&nbsp;Hua Qian,&nbsp;Yuwen Shi,&nbsp;Yanbing Li","doi":"10.1111/1753-0407.70273","DOIUrl":"https://doi.org/10.1111/1753-0407.70273","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study assessed the real-world effectiveness and safety of a fixed-dose combination (FDC) of metformin and empagliflozin in Chinese patients with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective, multicenter, real-world study enrolled consecutive patients with T2DM treated with the FDC of metformin and empagliflozin between August 2023 and August 2025 across 50 clinical centers in China. The primary endpoint was the 6-month glycemic clinical control rate (HbA1c &lt; 7.0%). The safety outcome included adverse events (AEs), major adverse cardiovascular events (MACEs), and major adverse kidney events (MAKEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 2602 adults with T2DM were enrolled. The full-analysis sets included 1719 patients, respectively. Median age was 54 years, median body mass index (BMI) was 25.7 kg/m², median HbA1c was 8.3%, and median diabetes duration was 3 years; 34% of patients were female. At 6 months, the proportion of patients achieving HbA1c &lt; 7.0% increased from 20.2% to 58.9%, with median HbA1c falling by about 1.1%–1.2%. Treatment also lowered fasting plasma glucose, body weight, and waist and hip circumference, and modestly reduced blood pressure, improving blood pressure control and shifting the BMI distribution toward normal weight. Subgroup analyses showed higher HbA1c target attainment in younger patients, those with lower baseline HbA1c, and those with higher BMI. Most patients remained on metformin/empagliflozin. AEs, MACEs, MAKEs, ketoacidosis, and genitourinary infections were infrequent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this large-scale, real-world study in a Chinese population, the empagliflozin and metformin FDC improved long-term HbA1c control and was well tolerated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Disease Silos to Integrated Cardiometabolic Care: Diabetes, Vascular Disease, and Heart Failure","authors":"Zachary T. Bloomgarden,&nbsp;Yehuda Handelsman","doi":"10.1111/1753-0407.70272","DOIUrl":"10.1111/1753-0407.70272","url":null,"abstract":"&lt;p&gt;The Tenth Heart in Diabetes (HiD) meeting, held in Philadelphia, Pennsylvania, June 19–21, 2026, offered a clinical approach to the complex cardio-renal-metabolic (CRM) patient. Features of CRM disease include diabetes, insulin resistance, obesity, chronic kidney disease, atherosclerosis, heart failure, fatty liver disease, vascular inflammation, and neurohormonal activation, typically with multiple coexisting conditions which interact biologically and increasingly share treatments. The American Heart Association cardiovascular-kidney-metabolic (CKM) framework provides a formal pathophysiologic structure, while HiD emphasizes the practical task of managing these problems together [&lt;span&gt;1, 2&lt;/span&gt;] Figure 1.&lt;/p&gt;&lt;p&gt;The meeting's strongest message was not that every disorder should be collapsed into a single syndrome. Each patient's risk should be addressed by integrating glucose, lipids, blood pressure, albuminuria, body weight, liver disease, and heart failure instead of treating them as unrelated targets, recognizing that multiple treatment approaches have benefits crossing traditional specialty boundaries. Earlier detection and complementary treatment are justified only when they improve clinical decisions, implementation, and outcomes Figure 2.&lt;/p&gt;&lt;p&gt;The historical organization of medicine is anatomical: the heart, cardiology, the kidney, nephrology, glucose, and endocrinology. The biological organization of disease is different. Insulin resistance, adipose dysfunction, endothelial injury, inflammation, fibrosis, sympathetic activation, aldosterone signaling, impaired natriuresis, and social disadvantage do not respect departmental boundaries. Albuminuria predicts cardiovascular events; heart failure risk rises as kidney function falls; obesity drives diabetes, metabolic-associated steatotic liver disease (MASLD), atrial fibrillation, and heart failure with preserved ejection fraction (HFpEF); and therapies first developed for glucose lowering now improve kidney, heart failure, liver, and atherosclerotic outcomes. The AHA definition of CKM syndrome—pathophysiologic interactions among metabolic risk factors, CKD, and the cardiovascular system leading to multiorgan dysfunction and adverse cardiovascular outcomes—captures this reality [&lt;span&gt;1, 2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;HiD is therefore more than a meeting title. Its conceptual legitimacy rests on three observations. First, the same patients repeatedly cross specialty boundaries. Second, common pathways generate correlated organ injury. Third, the strongest therapies have become cross-organ interventions. SGLT2 inhibitors, GLP-1 receptor agonists, nonsteroidal MRAs, intensive lipid lowering, and effective obesity treatment cannot be assigned neatly to one organ. The field is moving from “Which specialist owns this disease?” toward “Which combination of mechanisms, tests, and implementation supports this patient's risk trajectory?”&lt;/p&gt;&lt;p&gt;CKM/CRM should not become a vague container into which every chro","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Vitamin D Deficiency and Its Association With PTH and Type 1 Diabetes Mellitus (T1DM) in a Multicultural Pediatric Population in the United Arab Emirates, 2023","authors":"Mariam K. Ibrahim,&nbsp;Sara Khan,&nbsp;Karim Siam,&nbsp;Shiefa Sequeria,&nbsp;Rubina Lone","doi":"10.1111/1753-0407.70219","DOIUrl":"10.1111/1753-0407.70219","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>The vitamin D and parathyroid pathways are intrinsically linked to the regulation of calcium levels within a physiological range. Type 1 Diabetic patients are in turn theoretically impacted by these factors due to insulin's dependence on calcium for its function. This paper investigates the relationship between Type 1 Diabetes Mellitus, vitamin D deficiency, and parathyroid hormone levels in the pediatric population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This is a cross-sectional study with 102 participants aged 3–18 years old who were selected from Salama and Cerner patient databases at Al Jalila Children's Specialty Hospital (Dubai Health). Inclusion criteria for selection were based on participants' Type 1 Diabetes Mellitus status and Hemoglobin A1c levels. Furthermore, other factors such as phosphate levels, calcium levels, and comorbidities were collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of vitamin D insufficiency was 73.3%, with 63.2% of patients reporting normal parathyroid hormone levels. There was no significant correlation between vitamin D and parathyroid hormone levels (<i>χ</i> = 7.7, <i>p</i> = 0.103). Of the diabetic patients with insufficient vitamin D levels and normal parathyroid hormone levels, 83.3% had normal calcium levels (<i>χ</i> = 22.986, <i>p</i> = 0.028). There was no significant correlation between vitamin D, parathyroid hormone, and other factors such as phosphate levels, vitamin D supplementation, and comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Type 1 Diabetes pediatric patients exhibited the ability to regulate calcium homeostasis through parathyroid hormone regulation despite having insufficient vitamin D levels. However, such compensatory mechanisms may manifest as long-term complications without early intervention. Further investigations should be conducted to investigate the causal pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor on: “Effect of Topical Application of Antimicrobial Peptide PL-5 (Peceleganan) Spray on Mild to Moderate Infection of Diabetic Foot Ulcers: A Multicenter, Randomized, Double- Blinded, Placebo-Controlled Clinical Trial”","authors":"Xiang Ma,&nbsp;Qingqing Shan","doi":"10.1111/1753-0407.70270","DOIUrl":"10.1111/1753-0407.70270","url":null,"abstract":"&lt;p&gt;We read with great interest the multicenter, randomized, double-blind, placebo-controlled trial by Qian et al. evaluating the topical antimicrobial peptide PL-5 spray for mild-to-moderate diabetic foot ulcer infections [&lt;span&gt;1&lt;/span&gt;]. The study's finding of superior clinical response rates and promising clearance of drug-resistant bacteria represents a potentially valuable contribution to wound care. However, we wish to raise several methodological concerns that may affect the interpretation of the results.&lt;/p&gt;&lt;p&gt;First, we are concerned about the baseline imbalance in wound infection scores between groups. As shown in Table 2, the placebo group had a significantly higher median infection score at baseline (3.0 vs. 2.5, &lt;i&gt;p&lt;/i&gt; = 0.0073), showing more severe infection at enrollment. While the authors attempted to adjust for this using a mixed-effects model, statistical adjustment cannot fully eliminate the inherent bias introduced by baseline prognostic imbalance in a randomized trial [&lt;span&gt;2&lt;/span&gt;]. This variation suggests that randomization may not have been stratified by infection severity, which may be compromising the comparability of the two groups. Given that prognosis is strongly correlated with baseline infection severity, this design flaw fundamentally compromises the robustness of the primary endpoint conclusion [&lt;span&gt;3&lt;/span&gt;]. As Coskinas et al. demonstrated, post hoc decisions to adjust for observed imbalances risk inflating the probability of falsely declaring treatment superiority [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Second, the primary efficacy endpoint—defined as a ≥ 50% reduction in wound infection score—provokes concerns about subjectivity. The composite score includes components such as erythema, induration, tenderness, and pain, which are intrinsically subjective and susceptible to assessment bias [&lt;span&gt;5&lt;/span&gt;]. Although the trial was double-blinded, blinding is less effective in controlling bias for subjective outcomes than for objective ones [&lt;span&gt;6&lt;/span&gt;]. The absence of objective inflammatory markers (e.g., CRP, PCT) as corroborative evidence further weakens the validity of the primary endpoint [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Third, the use of a placebo control in this context raises both ethical and clinical questions. Given that standard topical antimicrobials (e.g., silver sulfadiazine, mupirocin) are widely available, placebo-controlled designs may expose patients in the control group to inferior care [&lt;span&gt;8&lt;/span&gt;]. Furthermore, clinicians are more interested in knowing whether PL-5 offers advantages over existing treatments rather than over placebo. The absence of an active comparator limits the clinical significance of the findings.&lt;/p&gt;&lt;p&gt;Fourth, the details of the screening failure warrant clarification. Figure 1 indicates that 12 of 60 screened patients did not enroll, of whom 10 did not meet the inclusion criteria. However, the specific reasons for these exclusions—whether due to infection severity, glycemic control,","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Diabetic Ketoacidosis as the Initial Presentation of m.3243A>G-Related Mitochondrial Diabetes in a 19-Year-Old Woman","authors":"Rathana Ly,&nbsp;Toshihiro Kobayashi,&nbsp;Kensaku Fukunaga,&nbsp;Takanobu Saheki,&nbsp;Takafumi Yoshimura,&nbsp;Eri Harada,&nbsp;Keisuke Takahashi,&nbsp;Seisuke Sato,&nbsp;Wenyi Jiang,&nbsp;Haotian Zhang,&nbsp;Hitomi Imachi,&nbsp;Koji Murao","doi":"10.1111/1753-0407.70268","DOIUrl":"10.1111/1753-0407.70268","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triangulating the Skeletal Safety of SGLT2 Inhibitors in Diabetes","authors":"Bin Huang,&nbsp;Shujie Yu,&nbsp;Anran Su,&nbsp;Yi Zheng,&nbsp;Yue Teng,&nbsp;Wei Wang","doi":"10.1111/1753-0407.70265","DOIUrl":"https://doi.org/10.1111/1753-0407.70265","url":null,"abstract":"&lt;p&gt;Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide established cardiorenal benefit, but skeletal safety remains clinically relevant because type 2 diabetes confers excess fracture risk that is not fully captured by bone mineral density (BMD) [&lt;span&gt;1&lt;/span&gt;]. Although updated randomized-trial meta-analysis and comparative cohort studies generally do not show increased fracture risk, uncertainty persists because skeletal events are uncommon and observational estimates remain vulnerable to confounding [&lt;span&gt;2-4&lt;/span&gt;]. We therefore triangulated evidence from sources with distinct bias structures.&lt;/p&gt;&lt;p&gt;We analyzed latest-version reports in FAERS (Q1 2004-Q2 2025) and JADER, comparing SGLT2 inhibitor suspect reports with all other reports and, separately, SGLT2 inhibitor-only with dipeptidyl peptidase-4 inhibitor-only reports. A signal required both the lower 95% confidence bound of the reporting odds ratio (ROR) to exceed 1 and IC025 to exceed 0. We additionally examined a 1:3 propensity score-matched cross-sectional DXA cohort (61 users; 180 non-users), survey-weighted NHANES 2013–2018 adults with diabetes (59 users), and kidney SLC5A2 expression quantitative trait locus-based Mendelian randomization (MR), including multivariable MR adjusted for estimated glomerular filtration rate. Detailed methods and complete estimates are provided in Supporting Information.&lt;/p&gt;&lt;p&gt;Results are summarized in Table 1. FAERS showed no positive disproportionality for fracture or any bone event in either comparison. JADER was null in all-background analyses; active-comparator estimates were modestly elevated for fracture (ROR 1.41, 95% CI 1.03–1.93) and any bone event (ROR 1.40, 95% CI 1.03–1.91), but both false discovery rate-adjusted &lt;i&gt;p&lt;/i&gt; values were 0.069. In the matched cohort, adjusted differences in total hip, femoral neck, and lumbar spine BMD were small and nonsignificant. NHANES showed no reproducible association with femoral BMD, although the BMI-adjusted total-femur estimate was imprecise and near the null threshold (beta = −0.0509 g/cm&lt;sup&gt;2&lt;/sup&gt;, 95% CI −0.1031 to 0.0014; &lt;i&gt;p&lt;/i&gt; = 0.057). MR analyses did not support associations between genetically proxied kidney SLC5A2 expression and BMD, osteoporosis, or fracture.&lt;/p&gt;&lt;p&gt;The discordant JADER active-comparator finding should be treated as signal-generating rather than causal: Spontaneous-reporting systems lack exposure denominators and are sensitive to regional reporting patterns, channeling, and comparator composition [&lt;span&gt;5&lt;/span&gt;]. Conversely, null findings across heterogeneous sources do not establish absence of risk, particularly for individual drugs, prolonged exposure, or patients with frailty, kidney disease, or prior fracture. The cross-sectional DXA design, few NHANES users, and limited target-proximal instruments further constrain precision.&lt;/p&gt;&lt;p&gt;Overall, this triangulation found no consistent adverse skeletal signal for SGLT2 inhibitors. The findings support current comp","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 Inhibitors Are Associated With Suppression of the Sema3A/NRP1/Plexin-A1 Signaling Axis in Postmenopausal Women With Type 2 Diabetes: Evidence From Propensity Score-Matched Analysis","authors":"Sertas Erarslan,&nbsp;Burcu Cosgun Bora","doi":"10.1111/1753-0407.70262","DOIUrl":"https://doi.org/10.1111/1753-0407.70262","url":null,"abstract":"<p>Propensity score-matched comparison of 23 SGLT2 inhibitor users and 23 non-users revealed that SGLT2 inhibitor use was associated with significantly lower Neuropilin-1 (NRP1) levels (74.25 vs. 87.61 ng/mL; <i>p</i> = 0.015) and a higher Sema3A/NRP1 ratio (0.14 vs. 0.12; <i>p</i> = 0.006), indicating functional impairment of the Sema3A/NRP1/Plexin-A1 bone signaling axis with compensatory Sema3A upregulation. Classical bone turnover markers (P1NP, CTX, coupling index) and DXA-derived BMD did not significantly differ between groups. These findings suggest that SGLT2 inhibitors may perturb the Sema3A/NRP1/Plexin-A1 axis before detectable changes in conventional markers, offering a novel mechanistic perspective to explain the inconsistency between existing meta-analyses on SGLT2 inhibitor bone safety.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TBC1D4-Related Monogenic Diabetes: Molecular Mechanisms, Clinical Recognition, and Therapeutic Implications","authors":"Wenjing Wang,&nbsp;Lidan Ma,&nbsp;Bingzi Dong,&nbsp;Peihan Gao,&nbsp;Xiaofang Sun","doi":"10.1111/1753-0407.70266","DOIUrl":"https://doi.org/10.1111/1753-0407.70266","url":null,"abstract":"<p>Monogenic diabetes caused by <i>TBC1D4</i> mutations is a relatively rare hereditary disorder of glucose metabolism that has increasingly gained attention in recent years. The protein encoded by this gene plays a pivotal regulatory role in glucose transport within skeletal muscle and adipose tissue; its dysfunction leads to significant insulin resistance and glucose dysregulation characterized by predominant postprandial hyperglycemia. Accumulating research indicates that <i>TBC1D4</i> mutations may contribute to metabolic disturbances by impairing glucose transport and blunting cellular insulin sensitivity. Patients typically present in adolescence or young adulthood, often accompanied by metabolic comorbidities such as obesity, dyslipidemia, fatty liver, and hyperuricemia; some may also manifest acanthosis nigricans or polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome)-like features. Due to frequent clinical misdiagnosis or underdiagnosis, a comprehensive evaluation incorporating age of onset, family history, glycemic characteristics, autoantibody status, and genetic testing is essential for accurate diagnosis. Currently, specific targeted therapies are lacking, and lifestyle intervention remains the cornerstone of management, with exercise intervention being particularly vital for improving insulin resistance. This review focuses on the molecular biological characteristics of the <i>TBC1D4</i> gene and its encoded protein, mutation types, pathogenic mechanisms, clinical manifestations, and diagnostic strategies, as well as therapeutic advances. It aims to systematically summarize the research progress on <i>TBC1D4</i>-related monogenic diabetes to enhance clinical awareness and provide a reference for early identification, precise diagnosis, and individualized treatment.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 Medicines in Perspective: Approaches to Optimize Outcome","authors":"Zachary Bloomgarden","doi":"10.1111/1753-0407.70264","DOIUrl":"https://doi.org/10.1111/1753-0407.70264","url":null,"abstract":"&lt;p&gt;The recent history of glucagon-like peptide-1 (GLP-1)-based therapy has been told largely as a succession of efficacy milestones: greater HbA1c lowering, greater weight loss, and progressively broader cardiovascular and kidney benefits. The newest literature suggests that this is an incomplete description. The clinically important question is no longer, “How much weight can be lost?” A more complex set of questions must be asked, pertaining to which biological effects matter for a particular patient, how durable are they, and what should be combined with GLP-1 receptor activation (RA) to improve the quality rather than simply the magnitude of response?&lt;/p&gt;&lt;p&gt;Two developments could materially alter how GLP-1 therapies are delivered. First, semaglutide was recently reformulated to require a lower oral dose for the same effect [&lt;span&gt;1&lt;/span&gt;], and another agent, orfoglipron, has been brought to market in the US [&lt;span&gt;2&lt;/span&gt;]. Orfoglipron, along with aleniglipron and elecoglipron, allows oral dosing of nonpeptide small-molecule GLP-1RA with clinically meaningful weight and glucose lowering [&lt;span&gt;3, 4&lt;/span&gt;]. The small molecule GLP-1RAs can be taken without the food, water, and post-dose restrictions required for oral semaglutide, and all the agents are associated with appreciable placebo-adjusted weight loss. Oral treatment, particularly using small molecules, could reduce barriers related to injections, refrigeration, manufacturing complexity, and supply.&lt;/p&gt;&lt;p&gt;Second, chronic therapy is beginning to be studied in terms of both induction and maintenance of treatment rather than as an indefinite fixed-dose prescription. In SURMOUNT-MAINTAIN, participants who continued maximum-tolerated tirzepatide after initial weight loss essentially maintained their weight, whereas withdrawal produced substantial regain. De-escalation to 5 mg preserved a meaningful, although incomplete, portion of the benefit [&lt;span&gt;5&lt;/span&gt;]. This raises the clinically important possibility that after effective induction some patients may be managed with lower doses, preserving the desired metabolic and functional result. A recent review emphasizes that cost, access, gastrointestinal intolerance, and perceived lack of benefit commonly lead to treatment interruption, followed by weight regain and deterioration of glycemic and cardiometabolic markers [&lt;span&gt;6&lt;/span&gt;]. Persistence and affordability are important aspects of therapeutic efficacy, not merely implementation details.&lt;/p&gt;&lt;p&gt;A number of studies challenge the simple hypothesis suggesting that GLP-1RA causes weight loss, which in turn explains all subsequent benefit.&lt;/p&gt;&lt;p&gt;Consider the SYNCHRONIZE trial of the oxyntomodulin analog survodutide, which activates both the glucagon receptor and the GLP-1 receptor. Although the agent was associated with a lower mean change in body weight than that expected with the class, changing at Week 76 by just −12.2%, it led to a 63.1% reduction in liver fat, considerably greater tha","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"18 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}