Journal of Diabetes Investigation最新文献

{"title":"Diabetic foot ulcer-related amputation is associated with twofold increased risk of cardiovascular disease: A Korean National Health Information Database Study","authors":"Jinsun Jang,&nbsp;Bong-Seong Kim,&nbsp;Hye Won Yang,&nbsp;Heejun Son,&nbsp;Dong Yeon Lee,&nbsp;Min Gyu Kyung,&nbsp;Hwan Jun Jae,&nbsp;Saebeom Hur,&nbsp;Sang Wha Kim,&nbsp;Sanghyun Ahn,&nbsp;Kyung-Do Han,&nbsp;Soo Heon Kwak","doi":"10.1111/jdi.70268","DOIUrl":"10.1111/jdi.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To quantify the risk of cardiovascular disease (CVD) and all-cause mortality associated with diabetic foot ulcer (DFU)-related amputation using a large-scale, nationally representative cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This longitudinal study included individuals with diabetes who underwent standardized national health checkups between 2009 and 2012, with follow-up data obtained from the Korean National Health Insurance Service claims database. CVD was defined as an incident myocardial infarction or stroke occurring after the index health checkup. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for CVD and mortality in individuals with DFU-related amputation compared with those with diabetes but without amputation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1,229,689 individuals with diabetes, 1,486 (0.12%) had a DFU-related amputation at baseline. The median follow-up was 8.2 years in the non-amputation group and 6.7 years in the DFU-related amputation group. People with DFU-related amputation had a significantly higher incidence rate of CVD compared with those without DFU-related amputation (32.6 vs. 11.0 per 1000 person-years) with a HR of 1.9 (95% CI 1.6–2.1). The HRs for myocardial infarction and stroke were 2.2 (95% CI 1.9–2.6) and 1.6 (95% CI 1.4–1.8), respectively. All-cause mortality significantly increased in people with DFU-related amputation compared with those without, with an HR of 2.1 (95% CI 1.9–2.3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this nationwide population-based cohort, DFU-related amputation was associated with nearly a twofold increased risk of cardiovascular events and mortality. These findings underscore the importance of comprehensive cardiovascular risk assessment and management in patients with diabetic foot complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 6","pages":"1024-1033"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508342","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":"Data-driven cluster analysis of adults with prediabetes: Findings from the Japan diabetes prevention study","authors":"Naoki Sakane,&nbsp;Kaoru Takahashi,&nbsp;Akiko Suganuma,&nbsp;Masayuki Domichi,&nbsp;Kazuyo Tsushita,&nbsp;Hideshi Kuzuya","doi":"10.1111/jdi.70302","DOIUrl":"10.1111/jdi.70302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To identify distinct metabolic subtypes among Japanese adults with prediabetes and examine their association with type 2 diabetes (T2D) risk and response to lifestyle interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from 295 adults with impaired glucose tolerance (mean age 50.4 ± 14.6 years) enrolled in the Japanese Diabetes Prevention Program, a randomized controlled trial with up to 6 years of follow-up, were analyzed. Participants with a history of diabetes, gastrectomy, or exercise contraindications were excluded from the study. <i>K</i>-means clustering (<i>k</i> = 2–5) was applied to baseline indices, including HbA1c, HOMA-β, HOMA-IR, and HDL-cholesterol. Principal component analysis (PCA) was used for interpretation. Incident T2D was defined as a repeat 75-g OGTT. Kaplan–Meier and Cox models were adjusted for baseline HbA1c estimated cumulative incidence and hazard ratios (HRs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three clusters emerged at <i>k</i> = 3, and PCA (two components explaining 68.0% of the variance) clearly separated the clusters based on insulin resistance and glycemic indices. Cluster 1, Metabolically Resilient Prediabetes (<i>n</i> = 127, MRP), showed the most favorable metabolic profile and lowest T2D risk. Cluster 2, Insulin-Insufficient Prediabetes (<i>n</i> = 109, IIP), exhibited reduced β-cell function and the highest T2D risk, but derived the greatest benefit from lifestyle intervention (adjusted HR 0.40, 95% CI 0.17–0.95, <i>P</i> &lt; 0.05). Cluster 3, Severe Insulin-Resistant Prediabetes (SIRP; <i>n</i> = 59), displayed obesity-related insulin resistance and an intermediate risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Unsupervised clustering identified three biologically distinct prediabetic subtypes that differed in diabetes risk and intervention responsiveness, supporting a precision prevention framework for Japanese adults with prediabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 6","pages":"961-969"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696926","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":"Comparative efficacy and safety of three fixed-ratio combination products in type 2 diabetes: A network meta-analysis","authors":"Xiaomei Wang,&nbsp;Jiali Qin,&nbsp;Yang Liu,&nbsp;Xianying Wang","doi":"10.1111/jdi.70293","DOIUrl":"10.1111/jdi.70293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To systematically evaluate and compare the efficacy and safety of three fixed-ratio combination products—insulin degludec/liraglutide (IDegLira), insulin glargine/lixisenatide (iGlarLixi), and insulin degludec/insulin aspart (IDegAsp)—in patients with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP up to July 2025 for randomized controlled trials (RCTs) comparing the three combinations of primary interest (IDegLira, iGlarLixi, IDegAsp) and their individual components (insulin degludec, insulin glargine, liraglutide, and lixisenatide). Inclusion of the individual components enabled indirect comparisons. Data extraction, risk-of-bias assessment, and GRADE evaluation were performed. Network meta-analysis was conducted using Stata 14.0, with treatments ranked by the surface under the cumulative ranking curve (SUCRA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one RCTs involving 12,815 patients were included. Both IDegLira (OR = 1.69, 95% CI: 1.08–2.65) and iGlarLixi (OR = 1.67, 95% CI: 1.17–2.37) had a higher incidence of treatment-emergent adverse events (TEAEs) than IDegAsp; no other significant pairwise differences were observed. Based on SUCRA values, which provide a probabilistic ranking (indicating the likelihood of being the best rather than direct statistical superiority), IDegLira had the highest probability of being optimal for reducing HbA1c (89.4%), fasting plasma glucose (81.8%), and incidence of hypoglycemic events (57.6%), while IDegAsp ranked highest regarding the incidence of TEAEs (97.9%). Inconsistency in the hypoglycemia network, likely due to varied definitions, warrants cautious interpretation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among the three fixed-ratio combination products, IDegLira appears most effective for glycemic control (in terms of HbA1c and FPG reduction), whereas IDegAsp demonstrates the best safety profile regarding incidence of TEAEs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 6","pages":"979-988"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525155","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":"Interpretable machine learning models based on CMR radiomics for predicting left ventricular diastolic dysfunction in patients with metabolic-associated steatotic liver disease and type 2 diabetes mellitus","authors":"Jinying Xia,&nbsp;Shaoyi Leng,&nbsp;Bin Xu,&nbsp;Guang Jin,&nbsp;Jianhui Li,&nbsp;Mingchen Zhang,&nbsp;Danzhen Yao,&nbsp;Ruiting Shen,&nbsp;Qifeng Hua","doi":"10.1111/jdi.70315","DOIUrl":"10.1111/jdi.70315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity-induced left ventricular diastolic dysfunction (LVDD), associated with ectopic fat and dysfunctional epicardial adipose tissue (EAT), is emerging as a key research area due to its increasing prevalence and links to metabolic-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM). This underscores the importance of early risk assessment and intervention to prevent the progression of LVDD. We developed an interpretable machine learning (ML) model combining cardiac magnetic resonance (CMR) radiomics and clinical data to assess LVDD risk in MASLD/T2DM patients, enabling proactive treatment customization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively analyzed 175 MASLD/T2DM patients, splitting them into training and external validation groups. After categorizing them as LVDD+ or LVDD-, we collected clinical data and extracted standardized CMR radiomics features to develop ML models. The optimal model was internally validated, interpreted using Shapley Additive Explanations (SHAP), and externally validated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LVDD prevalence was similar in both cohorts (45.5% vs 46.2%, χ² = 0.108, <i>P</i> = 0.743) among 175 MASLD/T2DM patients. The extreme gradient boosting (XGBoost) model, combining CMR radiomics and clinical data, outperformed in both internal and external validations. SHAP analysis revealed five critical determinants of LVDD: three radiomics features from CMR images and two clinical variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The XGBoost model, incorporating radiomics from CMR images and clinical data, outperformed other ML models in predicting LVDD risk in patients with T2DM and MASLD, enhancing risk assessment accuracy. This improvement allows for timely treatment adjustments, potentially preventing LVDD progression more effectively.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 6","pages":"1010-1023"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758440","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":"c-Jun N-terminal kinase 3 as a permissive regulator of β-cell incretin responsiveness","authors":"Yuji Yamazaki","doi":"10.1111/jdi.70297","DOIUrl":"10.1111/jdi.70297","url":null,"abstract":"&lt;p&gt;Incretin hormones were initially recognized for their ability to amplify insulin secretion in response to rising postprandial glucose levels. However, their biological significance is now understood to extend far beyond this classical incretin effect, encompassing broader roles in the regulation of glucose metabolism and energy balance. At the same time, the glucose-dependent insulinotropic actions of incretins have served as the principal foundation for the development of incretin-based therapies, which have become central to modern diabetes treatment and now extend beyond classical Glucagon-like peptide-1 (GLP-1) receptor agonists to include newer agents, such as dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists. Yet, as this therapeutic class continues to expand, important questions remain regarding the intracellular architecture that determines incretin responsiveness.&lt;/p&gt;&lt;p&gt;Within β-cells, c-jun N-terminal kinase (JNK) signaling has classically been discussed in the context of stress responses, inflammation, and apoptosis under pathophysiological conditions associated with diabetes. In this setting, JNK activation has often been linked to β-cell dysfunction and loss of functional β-cell mass. At the same time, however, the role of individual JNK isoforms is likely to be more nuanced than a uniformly deleterious model would suggest&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;. This broader context makes it particularly interesting to ask whether specific JNK family members may also participate in preserving β-cell signaling competence under metabolic or inflammatory stress.&lt;/p&gt;&lt;p&gt;In the current study, Louzada &lt;i&gt;et al&lt;/i&gt;. identify JNK3 as an important intracellular determinant of β-cell incretin responsiveness&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;. Using β-cell-specific JNK3 knockout mice together with complementary experiments in human islets, they demonstrate that loss of JNK3 impairs glucose tolerance and insulin secretion, particularly after oral glucose or nutrient challenge, while also reducing GLP-1 receptor expression and attenuating the cytoprotective actions of GLP-1 receptor activation (Figure 1). These findings position JNK3 not merely as a stress-related kinase, but as a key regulator of the intracellular signaling competence required for incretin action.&lt;/p&gt;&lt;p&gt;Incretin responsiveness should not be viewed as a simple linear output of canonical cyclic adenosine monophosphate (cAMP)-mediated signal amplification. Rather, it emerges from a finely regulated intracellular signaling network within the β-cell. Incretin action has classically been explained through canonical Gs-dependent cAMP generation. However, downstream responses have been shaped by broader signaling crosstalk, receptor trafficking, and context-dependent pathway engagement. In GLP-1 biology, β-cell signaling has increasingly been understood as context-dependent, with evidence that persistent depolarization or chronic hyperglycemic conditions can shift signaling beha","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 6","pages":"915-916"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525100","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 5","pages":"709-712"},"PeriodicalIF":3.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor in response to the association between COVID-19 and incident gestational diabetes (GDM): A population-based case-control study of the National Health Insurance Research Database in Taiwan","authors":"Komal Fatima,&nbsp;Ammara Shaikh,&nbsp;Adnan Memon","doi":"10.1111/jdi.70254","DOIUrl":"10.1111/jdi.70254","url":null,"abstract":"<p>Dear Editor,</p><p>We recently read with great interest the article by Lin <i>et al</i>. titled, “The association between COVID-19 and incident gestational diabetes (GDM),”<span>¹</span> which analyzed data from Taiwan's National Health Insurance Research Database (NHIRD). While the authors conducted a large population-based study using robust national data, certain methodological elements may limit the interpretation of the reported lack of association between COVID-19 infection and incident GDM.</p><p>First, misclassification of COVID-19 exposure represents a major concern. Infection status was identified solely through documented test results and healthcare records; consequently, asymptomatic or mildly symptomatic pregnant women who did not seek testing or medical care were regarded as unexposed. Such non-differential exposure misclassification would be expected to bias the observed associations toward the null. Causal inference frameworks highlight how the incomplete capture of exposure can significantly attenuate effect estimates when classification is imperfect<span>²</span>.</p><p>Second, key metabolic risk factors for GDM were not available in the NHIRD, including prepregnancy BMI, gestational weight gain, smoking status, and family history of diabetes. Although morbid obesity was included, it represents only extreme cases and is an inadequate substitute for continuous BMI. Observational studies using routine healthcare databases often lack these variables, making residual confounding likely<span>³</span>.</p><p>Third, the exclusion of pregnancies ending before 24 weeks could introduce selection bias. Since early pregnancy loss occurs among individuals infected with COVID-19, restricting the cohort to pregnancies proceeding 24 weeks may underrepresent those with early complications. While a recent meta-analysis showed a non-statistically significant trend toward higher odds of miscarriage (OR ≈ 1.44, 95% CI 0.96–2.18), another systematic review found no evidence of an increased risk (OR ≈ 1.10, 95% CI 0.81–1.48) but noted persistent low to moderate certainty of evidence. These potential selection effects remain an important consideration in case-control designs that require ongoing pregnancy for case ascertainment<span>⁴</span>.</p><p>In conclusion, although the study offers important insights in the medical field, addressing the limitations, such as exposure misclassification and the absence of granular metabolic data, could enhance the robustness of the findings. We appreciate the author's contribution to this significant topic.</p><p>The authors declare no conflict of interest.</p><p>Approval of the research protocol: None.</p><p>Informed consent: None.</p><p>Registry and registration number: None.</p><p>Animal studies: None.</p><p>Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083678","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":"Safety of anagliptin/metformin combination tablets evaluated by non-inferiority between pre- and post-serum lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment (AMELIO STUDY)","authors":"Hiroshi Kajio,&nbsp;Ryotaro Bouchi,&nbsp;Mitsuhisa Komatsu,&nbsp;Masanori Yamazaki,&nbsp;Daisuke Takarabe,&nbsp;Masahide Okamoto,&nbsp;Takahisa Tanaka,&nbsp;Toru Kitazawa,&nbsp;Hisayuki Katsuyama,&nbsp;Yasumichi Mori,&nbsp;Mitsuhiko Noda","doi":"10.1111/jdi.70253","DOIUrl":"10.1111/jdi.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>To investigate the safety of anagliptin/metformin combination tablets by evaluation of lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The participants of type 2 diabetes with creatinine-based eGFR (eGFRcr) of ≥45 and &lt;60 (mL/min/1.73 m²) (Group G3a) received anagliptin/metformin combination LD tablets (anagliptin: 100 mg, metformin hydrochloride: 250 mg/tablet) twice a day for 4 weeks. After 4 weeks, they received anagliptin/metformin combination HD tablets (anagliptin: 100 mg, metformin hydrochloride: 500 mg/tablet) twice daily until after 16 weeks. The participants (Group G3b) with baseline eGFRcr ≥30 and &lt;45 (mL/min/1.73 m²) received anagliptin/metformin combination LD tablets twice daily for 16 weeks. The serum lactic acid levels were examined at weeks 4, 8, and 16 after receiving anagliptin/metformin combination tablets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The change in serum lactic acid levels from baseline to 16 weeks was −0.09 [−0.28, 0.10] mmol/L (mean [95% confidence intervals]), not exceeding the pre-specified non-inferiority margin (0.7 mmol/L). No significant differences occurred in the change in serum lactic acid levels during all observation periods. Serum lactic acid levels exceeded 2.5 mmol/L in four participants (10.5%) and 5.0 mmol/L in one participant (2.6%) during the observation period. No participant had a plasma metformin exceeding 2.5 μg/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that the fixed-dose combination of anagliptin and metformin can be used safely in patients with type 2 diabetes complicated by moderate renal dysfunction. The advantage of this fixed-dose combination is also considered to be very large.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"636-648"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117183","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":"Re: Commentary on “Impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing cancer surgery: A single-center retrospective cohort study”","authors":"Tian Ruan","doi":"10.1111/jdi.70258","DOIUrl":"10.1111/jdi.70258","url":null,"abstract":"<p>Dear Editor-in-Chief,</p><p>We read with great interest the study by Fujimoto <i>et al</i>. [<span>1</span>], published in the <i>Journal of Diabetes Investigation</i> (2025, DOI: https://doi.org/10.1111/jdi.70224), examining the impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing gastrointestinal cancer surgery. This work makes a valuable contribution to geriatric oncology by emphasizing that reduced physical function, particularly weakened grip strength, emerges as a more significant independent predictor of adverse postoperative outcomes than current diabetes mellitus status in elderly surgical patients.</p><p>We commend the authors' finding that current diabetes mellitus status does not independently predict postoperative survival when physical function is accounted for, a clinically reassuring result that challenges the traditional assumption of diabetes as a major independent surgical risk factor. This observation underscores the paramount importance of comprehensive geriatric assessment and targeted optimization of physical function in all older patients undergoing cancer surgery, regardless of glycemic status.</p><p>This work was supported by the Yunnan Provincial Department of Education Science Research Fund (Grant No. 2024J2133) and the Yunnan Medical Health College University-level Research Project Fund (Grant No. 2024Y010).</p><p>This manuscript is a commentary on a previously published article and does not involve any original research with human participants or animals. Therefore, ethical approval was not required for this work.</p><p>Approval of the research protocol: Not applicable. This manuscript is a commentary on a previously published article and does not involve any original research with human participants.</p><p>Informed consent: Not applicable. No human participants were involved in this work.</p><p>Registry and the registration no. of the study/trial: Not applicable. This is a letter to the editor/commentary, not a clinical trial or registered study.</p><p>Animal studies: Not applicable. No animal studies were conducted.</p><p>Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"703-704"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123158","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":"Characterization of extracellular and membrane potentials in imeglimin-treated islets","authors":"Asuka Tsurumoto,&nbsp;Ryota Inoue,&nbsp;Esther Ong Yajima,&nbsp;Meng Zou,&nbsp;Junyu Luo,&nbsp;Takahiro Tsuno,&nbsp;Emi Ishida,&nbsp;Kohichi Matsunaga,&nbsp;Jun Shirakawa","doi":"10.1111/jdi.70265","DOIUrl":"10.1111/jdi.70265","url":null,"abstract":"<p>Glucose-stimulated insulin secretion (GSIS) in β cells depends critically on membrane depolarization–induced Ca²⁺ influx. Accordingly, the electrophysiological assessment of intact islets, where β cells act as functional syncytia, is essential for evaluating insulin secretory dynamics. Imeglimin, an oral agent used in treating type 2 diabetes, increases insulin secretion; however, its effects on β-cell electroactivity remain unclear. Here, we investigated extracellular and membrane potentials in imeglimin-treated mouse islets using microelectrode array (MEA) recordings and a plasma membrane potential indicator (PMPI). Imeglimin augmented first-phase insulin release and significantly increased the fraction of the plateau phase (FOPP), an MEA-derived parameter reflecting secretory competence, under 11.1 mM glucose. Consistent with these findings, the increase in PMPI fluorescence demonstrated enhanced membrane depolarization in response to imeglimin at high-glucose concentrations. These findings indicate that imeglimin potentiates β-cell electroactivity, thereby facilitating GSIS at the islet level.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 4","pages":"561-566"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199621","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}