Journal of Diabetes Investigation最新文献

{"title":"Methodological considerations on the associations of serum CTRP3 and CysC with bone metabolism in elderly patients with T2DM","authors":"Lijun Zhu, Bin Song","doi":"10.1111/jdi.70370","DOIUrl":"10.1111/jdi.70370","url":null,"abstract":"<p>We read with great interest the recent article by Wang <i>et al</i>.<span><sup>1</sup></span>, which reported that serum CTRP3 and CysC levels are significantly associated with glucose-lipid metabolism, bone turnover markers, and BMD in elderly patients with type 2 diabetes mellitus (T2DM) complicated by osteoporosis (OP). This study addresses an important clinical question, providing potential biomarkers for early identification of OP in this population. However, we have several methodological concerns that potentially threaten the validity of the conclusions.</p><p>First, the cross-sectional design limits causal interpretation of the associations between CTRP3/CysC and bone metabolism. While the study demonstrated correlations between serum CTRP3 and CysC with BMD and bone turnover markers (Figure 4a–n), temporal relationships cannot be established, and reverse causation remains possible. For example, elevated CysC may reflect early renal impairment, which itself could influence bone turnover independently of CTRP3 levels. Prospective cohort studies or repeated longitudinal measurements of CTRP3 and CysC are needed to confirm whether changes in these biomarkers precede alterations in bone metabolism rather than merely co-occurring with disease progression.</p><p>Second, potential confounding by unmeasured factors may bias the reported associations. Although the authors adjusted for age, gender, T2DM duration, and glucose-lipid parameters in multivariate logistic regression, critical covariates such as vitamin D status, physical activity, and direct measures of body composition (visceral fat or lean mass) were not included. Given that BMI alone cannot distinguish between fat and muscle mass<span><sup>2</sup></span>, residual confounding may exaggerate or obscure the relationships between serum biomarkers and OP risk. Future analyses incorporating these variables, alongside stratification by menopausal status, would provide more robust evidence for the independent predictive value of CTRP3 and CysC.</p><p>In summary, while the study by Wang <i>et al</i>. provides valuable insights into the potential utility of CTRP3 and CysC as markers of bone health in elderly T2DM patients, addressing these methodological limitations is essential to accurately interpret the findings and guide future clinical interventions and research.</p><p>Importantly, until longitudinal evidence becomes available, serum CTRP3 and CysC should be interpreted as associative rather than causal biomarkers of osteoporosis in T2DM, and clinicians should interpret them together with renal function (e.g., eGFR) and vitamin D status. Future prospective cohort studies or Mendelian randomization analyses may help clarify the causal relationships among CysC-related renal dysfunction, CTRP3-associated inflammation, and bone turnover abnormalities.</p><p>The authors declare no conflict of interest.</p><p>Approval of the research protocol: N/A.</p><p>Informed consent: N/A.</p><p>Approval","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325168","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":"Beyond weight loss: Preserving muscle health in the incretin era","authors":"Toshinori Imaizumi, Daisuke Yabe","doi":"10.1111/jdi.70414","DOIUrl":"10.1111/jdi.70414","url":null,"abstract":"<p>Incretin-based therapies have transformed the treatment of type 2 diabetes and obesity.<span><sup>1</sup></span> As the field has evolved from glucagon-like peptide-1 (GLP-1) receptor agonists to the glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide and, more recently, highly potent multi-agonists, the clinical challenge has begun to shift. The question is no longer whether substantial weight loss can be achieved, but whether it can be achieved while preserving muscle health, particularly in older adults. Retatrutide, an investigational triple GIP/GLP-1/glucagon receptor agonist, exemplifies this therapeutic progress. In a phase 2 body-composition sub-study involving people with type 2 diabetes, pooled 8-mg retatrutide regimens reduced body weight by approximately 16.8 kg over 36 weeks, compared with 2.1 kg with placebo and 0.8 kg with dulaglutide 1.5 mg.<span><sup>2</sup></span> Dual-energy X-ray absorptiometry (DXA) demonstrated an accompanying reduction of approximately 6.5 kg in lean mass, while most of the remaining weight loss reflected reductions in fat mass (Figure 1). This Commentary argues that the next challenge in the incretin era is not simply greater weight loss, but healthier weight loss—maximizing fat loss while preserving muscle health, particularly in older adults with type 2 diabetes.</p><p>Across clinical trials, reductions in lean or fat-free mass have consistently accounted for approximately one-quarter to two-fifths of total weight loss with incretin receptor agonists.<span><sup>3</sup></span> Whether this proportion is excessive remains debated. More importantly, the clinical relevance of lean-mass loss depends not only on its relative contribution to weight loss but also on its absolute magnitude and, critically, on the vulnerability of the individual receiving treatment. The clinical role of incretin receptor agonists is also expanding rapidly. Beyond glycemic and weight management, these agents reduce cardiovascular, heart failure, and chronic kidney disease risks, and have shown benefits in obstructive sleep apnea and metabolic dysfunction-associated steatohepatitis (MASH). As a result, they are increasingly prescribed across a broader range of clinical settings and for longer durations. Consequently, growing numbers of older adults—including those with pre-existing declines in muscle mass and function—are likely to receive these therapies, making preservation of muscle health an increasingly important clinical priority.</p><p>Older adults with type 2 diabetes are particularly vulnerable to muscle loss during rapid weight reduction. Sarcopenia—defined by the 2025 Asian Working Group for Sarcopenia (AWGS) as low muscle mass accompanied by low muscle strength—is more prevalent in people with diabetes and is associated with insulin resistance, falls, fractures, disability, loss of independence and mortality.<span><sup>4</sup></span> Reflecting these concerns, AWGS 2025 shifted its fo","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1658-1661"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704689","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":"USP30 inhibits wound healing in diabetic foot ulcers by promoting TRAF6-induced ferroptosis and angiogenesis inhibition","authors":"Jingjing Yuan,&nbsp;Shuang Sui,&nbsp;Zhenghua Yang,&nbsp;Kaiwen Zhang,&nbsp;Qiang Hu","doi":"10.1111/jdi.70384","DOIUrl":"10.1111/jdi.70384","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic foot ulcers (DFUs) frequently complicate diabetes. Ubiquitin-specific protease 30 (USP30), a key deubiquitinating enzyme, is implicated in diverse diseases. This study explores USP30's effects and mechanisms on DFUs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Tumor necrosis factor receptor-associated factor 6 (TRAF6), USP30, GPX4, and SLC7A11 protein levels were determined using western blot. TRAF6 mRNA level was assessed using real-time RT-qPCR. Cell proliferation and mortality were evaluated via the 5-Ethynyl-2′-deoxyuridine assay and TdT-mediated dUTP nick end labeling, respectively. Intracellular ferrous ion levels, malondialdehyde concentrations, and superoxide dismutase activity were measured with specialized cell metabolism kits, while intracellular reactive oxygen species levels were detected by flow cytometry. Cell migration was evaluated through wound healing assays, and tube formation was quantified using the tube formation method. Co-immunoprecipitation was conducted to validate USP30's regulatory effect on TRAF6 ubiquitination. Mouse models of DFU were established for <i>in vivo</i> validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TRAF6 was highly expressed in human umbilical vein endothelial cells (HUVECs) induced by high glucose (HG). TRAF6 knockdown enhanced cell proliferation, inhibited apoptosis and ferroptosis, and promoted cell migration and tubule formation in these cells. In HG-induced HUVECs, USP30 was also overexpressed and stabilized TRAF6 expression through deubiquitination. USP30 knockdown alleviated HG-induced injury in HUVECs by targeting TRAF6. Moreover, USP30 knockdown accelerated DFU wound healing and inhibited ferroptosis <i>in vivo</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>USP30 stabilizes TRAF6 via deubiquitination, triggering ferroptosis and suppressing angiogenesis, which ultimately impedes wound healing in DFU. This offers direct evidence for the modulatory role of USP30 in DFU.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1708-1725"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519671","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":"Accuracy, safety, and usability of a real-time continuous glucose monitoring system in pediatric diabetes management","authors":"Bingyan Cao,&nbsp;Zhe Su,&nbsp;Yi Wang,&nbsp;Yanhui Chen,&nbsp;Zhigang Hu,&nbsp;Mingsong Han,&nbsp;Chunxiu Gong,&nbsp;Yifei Mo","doi":"10.1111/jdi.70415","DOIUrl":"10.1111/jdi.70415","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The purpose of the study was to evaluate the accuracy, safety, and usability of a real-time Continuous Glucose Monitoring (CGM) system compared with venous blood glucose (vBG) in children and adolescents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study enrolled 81 participants aged from 3 to 17 at three sites in China. Two sensors (GS1, SiBionics, Shenzhen) were inserted on the back of each upper arm for up to 14 days for each participant. A variety of analyses were conducted for evaluating accuracy by comparing the CGM readings and vBG values, including 20%/20 agreement rate, the mean absolute relative difference (MARD), the Clarke error grid, and consensus error grid analyses. Safety was measured by adverse event (AE) monitoring. AEs were documented, and the incidence rate was calculated. Usability was evaluated by self-reported questionnaires.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from 80 participants were analyzed. Our results demonstrated high accuracy of the real-time CGM system. The 20%/20 agreement rate across all glycemic ranges was 93.9%. The MARD value was 8.7%. The results of the Clarke and consensus error grid analyses in zone A + B were 99.6% and 100%, respectively. The average score of usability was 95.3 ± 7.6, reflecting high satisfaction. The CGM also showed high safety, given that only 3 device-related AEs in 2 participants were reported , and no serious adverse events (SAEs) were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The real-time CGM system demonstrated high accuracy, safety, and usability in the glycemic monitoring of children and adolescents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1807-1815"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719737","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":"Diagnostic performance of SD-ΔRR during physical stressors for identifying diabetic sensorimotor polyneuropathy","authors":"Katsuyoshi Katayama,&nbsp;Haruhito A. Uchida,&nbsp;Toshihiko Nagao,&nbsp;Jun Eguchi,&nbsp;Kenji Tsuji,&nbsp;Yoshinori Matsumoto,&nbsp;Ichiro Nojima,&nbsp;Keiko Tanaka,&nbsp;Hidemi Takeuchi,&nbsp;Yasuhiro Onishi,&nbsp;Rika Takemoto,&nbsp;Satoshi Miyamoto,&nbsp;Kenichi Shikata,&nbsp;Jun Wada","doi":"10.1111/jdi.70399","DOIUrl":"10.1111/jdi.70399","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to evaluate the clinical efficacy of SD-ΔRR as a novel methodology for short-duration heart rate variability (HRV) assessment for the diagnosis of diabetic sensorimotor polyneuropathy (DSPN) in patients with diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Participants were assigned into normal fasting glucose (NFG) and diabetes groups. Patients with diabetes were further classified as patients with and without DSPN. Electrocardiograms were recorded at rest, during standing, and during deep breathing to evaluate HRV parameters. HRV was statistically compared between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 103 patients with diabetes (18 with DSPN, 85 without) and 52 with NFG were included in the analysis. SD-ΔRR values were comparable between the diabetes and NFG groups. However, among patients with diabetes, patients with DSPN had significantly lower SD-ΔRRs than patients without DSPN (<i>P</i> &lt; 0.05). Despite being age- and sex-matched, patients with DSPN had a significantly higher prevalence of hypertension and advanced chronic kidney disease than those without DSPN. Logistic regression analysis demonstrated that SD-ΔRRs during standing and deep breathing were significantly associated with the presence of DSPN in patients with diabetes (<i>P</i> &lt; 0.05 each). After adjustment for confounding factors, only SD-ΔRR during standing remained statistically significant. The cutoff value for SD-ΔRR during standing showed high sensitivity (83%), whereas that during deep breathing demonstrated high specificity (84%) for diagnosis of DSPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SD-ΔRR may serve as a clinically informative parameter for identifying DSPN in patients with diabetes. In combination with physical stressors, this metric offers distinct diagnostic advantages with high sensitivity and specificity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1770-1781"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547147","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 miR-145-5p/NRF2/SLC7A11 axis regulates ferroptosis-mediated renal tubular epithelial cell injury in diabetic nephropathy","authors":"Ganlin Wu,&nbsp;Yu Fang,&nbsp;Meirong Xu,&nbsp;Zuopeng Lu,&nbsp;Yu Cao,&nbsp;Yana Gao","doi":"10.1111/jdi.70397","DOIUrl":"10.1111/jdi.70397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study aimed to investigate the molecular mechanism by which the miR-145-5p/NRF2/SLC7A11 axis regulates ferroptosis-mediated renal tubular epithelial cell (RTEC) injury in diabetic nephropathy (DN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/KsJ-db/db mice were used as a murine DN model and treated with a miR-145-5p antagomir, adeno-associated virus carrying NRF2 short hairpin RNA (NRF2-shRNA), or the ferroptosis inducer (Erastin) or inhibitor (Ferrostatin-1). Renal function was assessed by measuring the urinary albumin-to-creatinine ratio, serum creatinine, and blood urea nitrogen. Renal histopathological injury and fibrosis were evaluated. <i>In vitro</i>, mouse RTECs (TCMK-1) were exposed to high glucose (HG) and transfected with a miR-145-5p antagomir or small interfering RNAs targeting NRF2 or SLC7A11. The interaction between miR-145-5p and NRF2 was validated using a dual-luciferase assay, while the binding of NRF2 to the SLC7A11 promoter was confirmed by chromatin immunoprecipitation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>miR-145-5p expression was upregulated in the kidneys of DN mice. Inhibition of miR-145-5p reduced ferroptosis, attenuated renal histological injury and fibrosis, and reversed epithelial-to-mesenchymal transition. These protective effects were partially abolished by Erastin treatment. Similarly, miR-145-5p inhibition suppressed HG-induced ferroptosis in TCMK-1 cells. Mechanistically, miR-145-5p directly targeted NRF2, and NRF2 bound to the promoter region of SLC7A11. Knockdown of either NRF2 or SLC7A11 partially reversed the anti-ferroptotic effects of miR-145-5p suppression. Furthermore, NRF2 silencing partially abrogated the protective effects of miR-145-5p inhibition in DN mice, while Ferrostatin-1 partially rescued renal tissue damage induced by NRF2 knockdown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Suppression of miR-145-5p alleviates renal injury in DN by inhibiting ferroptosis through activation of the NRF2/SLC7A11 axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1667-1685"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617590","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":"Combined sleep behaviors, mediating biomarkers, and incident vascular complications among individuals with type 2 diabetes: A prospective study in UK Biobank","authors":"Yanqiu Zou,&nbsp;Xia Jiang,&nbsp;Jinyu Zhou,&nbsp;Tao Han,&nbsp;Sirui Zheng,&nbsp;Mingshuang Tang,&nbsp;Yutong Wang,&nbsp;Lin Chen,&nbsp;Lingli Qiu,&nbsp;Xuan Wu,&nbsp;Zhixin Tan,&nbsp;Yunjie Liu,&nbsp;Bowen Lei,&nbsp;Xiaofeng Ma,&nbsp;Di Zhang,&nbsp;Jiaqiang Liao,&nbsp;Jiayuan Li,&nbsp;Ben Zhang,&nbsp;Mengyu Fan","doi":"10.1111/jdi.70396","DOIUrl":"10.1111/jdi.70396","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To prospectively examine how combined sleep behaviors affect vascular complications in type 2 diabetes, whether these associations are modified by disease severity, as well as the mediating roles of clinical biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 12,456 participants with type 2 diabetes from the UK Biobank were included. A sleep score was defined by: sleep duration, chronotype, insomnia, snoring, and daytime sleepiness. Cox regression models were used to examine the association between healthy sleep score and risk of vascular complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over 13.5 years, 1,878 macrovascular and 3,066 microvascular complications occurred. Compared with a healthy sleep score of 0–1, the multivariable-adjusted HRs (95% CIs) of the score 4–5 were 0.75 (0.63, 0.89) for macrovascular complications [coronary artery disease 0.72 (0.57, 0.91), stroke 0.92 (0.66, 1.28), peripheral artery disease 0.79 (0.56, 1.10)]; 0.86 (0.75, 0.99) for microvascular complications [neuropathy 0.62 (0.47, 0.83), nephropathy 1.01 (0.84, 1.21), retinopathy 0.84 (0.68, 1.03)]. The aggregated diabetes severity score (<i>P</i>_{<i>interaction</i>} = 0.037) significantly modified the association with microvascular complications. Total cholesterol, LDL-C, triglycerides, apolipoprotein B, and CRP collectively explained 11.34% (4.24%, 37.70%) of macrovascular associations [including 11.14% (2.85%, 43.03%) for coronary artery disease], while total bilirubin explained 3.57% (0.43%, 20.63%) of microvascular associations, collectively with triglycerides, GGT, and CRP mediating 9.33% (3.95%, 27.58%) for diabetic neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A healthy sleep pattern is associated with lower risks of vascular complications in type 2 diabetes, independent of traditional risk factors, and the association with microvascular complications is modified by diabetes severity. Lipid profiles and inflammatory factors partly mediate the favorable association.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1782-1793"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547144","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":"Real-world risk factors and clinical implications of early estimated glomerular filtration rate decline after sodium-glucose cotransporter-2 inhibitor therapy","authors":"Jangwook Lee,&nbsp;Dayoung Kang,&nbsp;Kyoung-Ah Kim,&nbsp;Han Seok Choi,&nbsp;Soomin Jo,&nbsp;Joeun Kim,&nbsp;Jae Yoon Park,&nbsp;Seung Eun Lee","doi":"10.1111/jdi.70410","DOIUrl":"10.1111/jdi.70410","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the prevalence, risk factors, estimated glomerular filtration rate trajectory, and clinical implications of the early estimated glomerular filtration rate dip after sodium-glucose cotransporter 2 inhibitors in a real-world population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 1,550 patients who received sodium-glucose cotransporter 2 inhibitor treatment at a single teaching hospital between 2014 and 2024. Patients were stratified into three groups based on early estimated glomerular filtration rate decline within the first 3 months of treatment: non-, moderate, and severe dippers (&lt;10%, 10%–30%, and ≥30%, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An early estimated glomerular filtration rate dip occurred in 21% of the patients; 17.6% were moderate dippers, and 3.5% were severe dippers. The risk factors for dipper classification included older age, atrial fibrillation, loop diuretic use, and high estimated glomerular filtration rate variability. Although the estimated glomerular filtration rate slopes declined progressively across dipper groups, the mean annual decline did not exceed age-expected changes even in the severe dipper group. Patients who discontinued sodium-glucose cotransporter 2 inhibitor therapy experienced a steeper decline than those who continued therapy. Three patients in the severe dipper group on concomitant loop diuretics experienced extreme estimated glomerular filtration rate reductions, which persisted during follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early dips and continued sodium-glucose cotransporter 2 inhibitor use are not generally associated with unfavorable outcomes. However, caution is warranted in frail or volume-sensitive patients, particularly with concomitant diuretics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1735-1743"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13431561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667785","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":"Association of glycation gap with hypoglycemia CGM indices, diabetic complications, and quality of life in Japanese type 2 diabetes patients","authors":"Satomi Sonoda,&nbsp;Yosuke Okada,&nbsp;Tomoya Mita,&nbsp;Keiichi Torimoto,&nbsp;Kenichi Tanaka,&nbsp;Fumiya Sato,&nbsp;Naoto Katakami,&nbsp;Hidenori Yoshii,&nbsp;Keiko Nishida,&nbsp;Shingo Nakayamada,&nbsp;Ryota Ishii,&nbsp;Masahiko Gosho,&nbsp;Iichiro Shimomura,&nbsp;Hirotaka Watada","doi":"10.1111/jdi.70403","DOIUrl":"10.1111/jdi.70403","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The glycation gap (GGap), defined as the discrepancy between glycated hemoglobin (HbA1c) and the value estimated from actual blood glucose level, is associated with diabetic complications, but its association with hypoglycemia remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the association between GGap and continuous glucose monitoring (CGM)-based hypoglycemic indices in patients with type 2 diabetes mellitus (T2DM). Baseline data from a multicenter cohort of 999 T2DM patients without cardiovascular disease were analyzed. The difference between HbA1c and estimated A1c (eA1c) was defined as the GGap, and various CGM indices were compared among low (≤0.16), medium (&lt;0.16 to ≤0.60), and high (&gt;0.60) GGap tertile groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the high GGap group, the average blood glucose was lower, while the Time Below Range &lt;3.9 mmol/L (TBR^&lt;3.9) and &lt;3.0 mmol/L (TBR^&lt;3.0), and low blood glucose index (LBGI) were higher than in the low and middle GGap groups. Patients with minimum blood glucose levels of &lt;3.9, &lt;3.0 mmol/L, and TBR^&lt;3.9 ≥ 4%, and TBR^&lt;3.0 ≥ 1% had significantly higher GGap values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the first study to show the strong association of high GGap with CGM-based hypoglycemic indices in T2DM. To achieve diabetes treatment that effectively prevents the progression of diabetic complications, it is essential to assess the GGap of the individual patient before intensifying diabetes management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 10","pages":"1794-1806"},"PeriodicalIF":3.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13417662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596915","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":"Associations of finerenone with reduced insulin resistance in patients with type 2 diabetes and chronic kidney disease: A real-world observational study","authors":"Xin Zhao,&nbsp;Bohan Liu,&nbsp;Ran Sun,&nbsp;Yaxuan Shi,&nbsp;Ya Liu","doi":"10.1111/jdi.70368","DOIUrl":"10.1111/jdi.70368","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>There is evidence linking activation of aldosterone activity with insulin resistance and metabolic risk factors. We hypothesized that finerenone, a nonsteroidal mineralocorticoid receptor antagonist, might improve insulin resistance in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In a single-center retrospective study including 45 patients with T2D and CKD treated with finerenone for 12 months between June 2023 and June 2025, we assessed insulin resistance using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and triglyceride-glucose (TYG) index along with metabolic and renal parameters measured at baseline, month-6, and month-12.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In these patients (<i>n</i> = 45; mean age 52.2 ± 13.9 years; 64.4% male; disease duration &gt;10 years in 48.9%; mean HbA1c 9.2 ± 2.5%; 60.0% treated with SGLT2i; 33.3% on GLP1RA), 12-month treatment with finerenone was associated with improvement in HOMA-IR (median [interquartile range]: baseline: 34.40 [12.84, 71.50], month-6: 25.22 [13.54, 78.19], month-12: 19.44 [9.51, 45.75] [<i>P</i> = 0.038, Friedman test]). TYG index (baseline: 9.49 [8.86, 10.29] month-6: 9.04 [8.54, 9.71], and month-12: 8.93 [8.44, 9.62] mg/dL [<i>P</i> &lt; 0.007 Friedman tset<span>]</span>); urinary albumin: creatinine ratio (baseline: 377.39 [127.80, 1327.29], month-6: 342.96 [87.58, 1442.12], month-12: 249.52 [68.04, 1198.03] mg/g [<i>p</i> = 0.05, Friedman test<span>]</span>) and estimated glomerular filtration rate (baseline: 112.01 [85.87, 120.00], month-6: 103.92 [75.25, 120.00], and month-12120.00 [80.46, 120.00] mL/min/1.73 m² [<i>P</i> = 0.002 Feirdman test<span>]</span>). There was no treatment discontinuations due to hyperkalemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In real-world practice, 12-month treatment with finerenone was associated with reduced insulin resistance and improved kidney function in patients with T2D and CKD and a manageable safety profile.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 9","pages":"1524-1532"},"PeriodicalIF":3.6,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300354","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}