Stress hyperglycemia ratio (SHR), calculated by dividing admission glucose levels by estimated chronic glucose levels, has emerged as a novel marker of glycemic stress. However, its prognostic value in patients hospitalized with COVID-19 remains unclear. This meta-analysis investigates the association between SHR and adverse outcomes in this population.
Materials and Methods
A comprehensive literature search was conducted in PubMed, Embase, and Web of Science databases for relevant observational studies. The primary outcome was a composite of ICU admission, invasive mechanical ventilation (IMV), and all-cause in-hospital mortality. Secondary outcomes included the individual components of the primary outcome. A random effects model was used to pool the results by incorporating heterogeneity.
Results
Seven studies involving 2,272 patients were included. Patients with a high SHR had a significantly higher risk of poor composite outcomes (risk ratio [RR]: 1.93, 95% confidence interval [CI]: 1.54–2.43; I2 = 56%). Subgroup analyses according to study country, age, sex, diabetic status, and cutoff of SHR showed consistent results (P for subgroup difference all >0.05). Secondary analyses revealed increased risks of ICU admission (RR: 1.77), IMV (RR: 1.87), and in-hospital mortality (RR: 2.25) in patients with a high SHR at admission.
Conclusions
High SHR at admission is independently associated with poor prognosis in patients hospitalized with COVID-19. However, as admission glucose levels in most studies were not standardized for fasting status, SHR may be influenced by postprandial hyperglycemia, which should be considered when interpreting its prognostic value.
{"title":"Association between stress hyperglycemia ratio and prognosis of patients hospitalized with COVID-19: A meta-analysis","authors":"Lizhan Chen, Mingming Wang, Jie Chen","doi":"10.1111/jdi.70146","DOIUrl":"10.1111/jdi.70146","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/introduction</h3>\u0000 \u0000 <p>Stress hyperglycemia ratio (SHR), calculated by dividing admission glucose levels by estimated chronic glucose levels, has emerged as a novel marker of glycemic stress. However, its prognostic value in patients hospitalized with COVID-19 remains unclear. This meta-analysis investigates the association between SHR and adverse outcomes in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted in PubMed, Embase, and Web of Science databases for relevant observational studies. The primary outcome was a composite of ICU admission, invasive mechanical ventilation (IMV), and all-cause in-hospital mortality. Secondary outcomes included the individual components of the primary outcome. A random effects model was used to pool the results by incorporating heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven studies involving 2,272 patients were included. Patients with a high SHR had a significantly higher risk of poor composite outcomes (risk ratio [RR]: 1.93, 95% confidence interval [CI]: 1.54–2.43; <i>I</i><sup>2</sup> = 56%). Subgroup analyses according to study country, age, sex, diabetic status, and cutoff of SHR showed consistent results (<i>P</i> for subgroup difference all >0.05). Secondary analyses revealed increased risks of ICU admission (RR: 1.77), IMV (RR: 1.87), and in-hospital mortality (RR: 2.25) in patients with a high SHR at admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High SHR at admission is independently associated with poor prognosis in patients hospitalized with COVID-19. However, as admission glucose levels in most studies were not standardized for fasting status, SHR may be influenced by postprandial hyperglycemia, which should be considered when interpreting its prognostic value.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"174-186"},"PeriodicalIF":3.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555901","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}
<p>Dear Editor,</p><p>We read with great interest the study by Chiu <i>et al</i>., which explored whether recent trajectories in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) predict renal responses after the initiation of sodium–glucose cotransporter-2 inhibitors (SGLT2i)<span><sup>1</sup></span>. The effort to stratify patients with otherwise “low-risk” renal profiles using dynamic markers is timely and has clear translational potential for tailoring early preventive therapies.</p><p>The authors provide persuasive evidence that the subgroup labeled as “glomerular injury” (rapid eGFR decline together with rising UACR) experienced lower adjusted hazards for a >30% eGFR decline (adjusted hazard ratio [HR] 0.384, 95% CI 0.199–0.740) and for UACR progression (adjusted hazard ratio 0.514, 95% CI 0.313–0.846) after SGLT2i exposure. This finding, together with the within-person improvement in eGFR slope after treatment (first- and second-year differences reaching statistical significance in the rapid decline groups), is an important signal that early dynamic surveillance can identify individuals who derive measurable renal trajectory benefits from SGLT2i.</p><p>Several aspects require further clarification to strengthen the causal inference and facilitate clinical adoption. First, the study would benefit from a more granular description of the clinical decision context for SGLT2i initiation; confounding by indication (e.g., initiation for cardiovascular risk, glycemic control, or perceived renal risk) may influence both baseline trajectories and subsequent outcomes<span><sup>2</sup></span>. Second, although the authors used a linear mixed model to estimate individual eGFR slopes, reporting model diagnostics (random-effects variance, number of measurements per subject, and sensitivity to nonlinearity) and an assessment of regression to the mean beyond the small subgroup with single post-treatment values would improve the confidence in slope estimates.</p><p>Third, the choice of dichotomous cut-off points (eGFR decline >2.5 mL/min/1.73 m<sup>2</sup>/year; UACR increase >30%) underpins group allocation and effect estimates. A brief justification linking these thresholds to absolute risk or decision thresholds used in prior prognostic studies would aid readers in judging external applicability. Fourth, adjustment sets excluded measures of blood pressure control, smoking status, and longitudinal medication adherence, which plausibly influence both albuminuria and eGFR trajectory<span><sup>3</sup></span>; consideration of these confounders or an instrumental-variable approach could reduce residual bias.</p><p>Finally, external validity beyond a single tertiary care registry in Taiwan deserves attention; replication in geographically and ethnically diverse cohorts and exploration of whether the predictive utility holds across different SGLT2i agents and doses will be important before recommending trajector
我们非常感兴趣地阅读了Chiu等人的研究，该研究探讨了最近估计肾小球滤过率（eGFR）和尿白蛋白与肌酐比（UACR）的轨迹是否可以预测钠-葡萄糖共转运蛋白-2抑制剂（sgltti）开始后的肾脏反应1。使用动态标记物对“低风险”肾脏特征患者进行分层的努力是及时的，并且在定制早期预防治疗方面具有明确的转化潜力。作者提供了有说服力的证据，表明SGLT2i暴露后，标记为“肾小球损伤”的亚组（eGFR快速下降和UACR上升）在eGFR下降>；30%（调整风险比[HR] 0.384, 95% CI 0.99 - 0.740）和UACR进展（调整风险比[HR] 0.514, 95% CI 0.313-0.846）的调整风险较低。这一发现，以及治疗后eGFR斜率的个人改善（快速下降组的第一年和第二年差异达到统计学意义），是一个重要的信号，表明早期动态监测可以识别出从SGLT2i中获得可测量的肾脏轨迹益处的个体。有几个方面需要进一步澄清，以加强因果推理，促进临床采用。首先，该研究将受益于对SGLT2i起始的临床决策背景的更细致的描述；由适应症引起的混淆（例如，心血管风险、血糖控制或感知到的肾脏风险）可能影响基线轨迹和随后的结果2。其次，尽管作者使用了线性混合模型来估计个体eGFR斜率，但报告模型诊断（随机效应方差、每个受试者的测量次数和对非线性的敏感性）和对回归均值的评估（超出了具有单一处理后值的小亚组）将提高斜率估计的可信度。第三，二分类截断点的选择（eGFR下降>；2.5 mL/min/1.73 m2/年；UACR增加>；30%）支持组分配和效果估计。将这些阈值与先前预后研究中使用的绝对风险或决策阈值联系起来的简短理由将有助于读者判断外部适用性。第四，调整集排除了血压控制、吸烟状况和纵向药物依从性的措施，这些措施可能会影响蛋白尿和eGFR轨迹3；考虑这些混杂因素或工具变量方法可以减少剩余偏差。最后，台湾单一三级医疗注册之外的外部有效性值得关注；在常规实践中推荐基于轨迹的SGLT2i起始治疗之前，在地理和种族不同的队列中进行复制以及探索预测效用是否适用于不同的SGLT2i药物和剂量将是重要的。总之，Chiu等人1提出了一个实用的框架，将短期肾脏动力学与治疗反应性结合起来，他们的结果值得前瞻性验证。我们感谢作者开启了这条临床可行的调查路线，并鼓励后续工作，解决上述问题，以帮助将这些观察结果转化为个性化的预防策略。作者声明无利益冲突。研究方案的批准：不需要。知情同意：不适用，因为本研究未收集或分析患者数据。注册表及注册编号研究/试验：无。动物研究：无。Shyam Sundar Sah：概念，方法，写作-原稿，写作-审查和编辑。Abhishek Kumbhalwar：审定，监督，项目管理，写作-原稿，写作-审查和编辑。不适用，因为本研究没有生成或分析数据。
{"title":"Comment on “The impact of dynamic kidney function prior to using sodium–glucose cotransporter-2 inhibitors in type 2 diabetes patients with low-risk renal disease progression”","authors":"Shyam Sundar Sah, Abhishek Kumbhalwar","doi":"10.1111/jdi.70194","DOIUrl":"10.1111/jdi.70194","url":null,"abstract":"<p>Dear Editor,</p><p>We read with great interest the study by Chiu <i>et al</i>., which explored whether recent trajectories in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) predict renal responses after the initiation of sodium–glucose cotransporter-2 inhibitors (SGLT2i)<span><sup>1</sup></span>. The effort to stratify patients with otherwise “low-risk” renal profiles using dynamic markers is timely and has clear translational potential for tailoring early preventive therapies.</p><p>The authors provide persuasive evidence that the subgroup labeled as “glomerular injury” (rapid eGFR decline together with rising UACR) experienced lower adjusted hazards for a >30% eGFR decline (adjusted hazard ratio [HR] 0.384, 95% CI 0.199–0.740) and for UACR progression (adjusted hazard ratio 0.514, 95% CI 0.313–0.846) after SGLT2i exposure. This finding, together with the within-person improvement in eGFR slope after treatment (first- and second-year differences reaching statistical significance in the rapid decline groups), is an important signal that early dynamic surveillance can identify individuals who derive measurable renal trajectory benefits from SGLT2i.</p><p>Several aspects require further clarification to strengthen the causal inference and facilitate clinical adoption. First, the study would benefit from a more granular description of the clinical decision context for SGLT2i initiation; confounding by indication (e.g., initiation for cardiovascular risk, glycemic control, or perceived renal risk) may influence both baseline trajectories and subsequent outcomes<span><sup>2</sup></span>. Second, although the authors used a linear mixed model to estimate individual eGFR slopes, reporting model diagnostics (random-effects variance, number of measurements per subject, and sensitivity to nonlinearity) and an assessment of regression to the mean beyond the small subgroup with single post-treatment values would improve the confidence in slope estimates.</p><p>Third, the choice of dichotomous cut-off points (eGFR decline >2.5 mL/min/1.73 m<sup>2</sup>/year; UACR increase >30%) underpins group allocation and effect estimates. A brief justification linking these thresholds to absolute risk or decision thresholds used in prior prognostic studies would aid readers in judging external applicability. Fourth, adjustment sets excluded measures of blood pressure control, smoking status, and longitudinal medication adherence, which plausibly influence both albuminuria and eGFR trajectory<span><sup>3</sup></span>; consideration of these confounders or an instrumental-variable approach could reduce residual bias.</p><p>Finally, external validity beyond a single tertiary care registry in Taiwan deserves attention; replication in geographically and ethnically diverse cohorts and exploration of whether the predictive utility holds across different SGLT2i agents and doses will be important before recommending trajector","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"191-192"},"PeriodicalIF":3.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522605","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}
Among patients with diabetes receiving sodium–glucose cotransporter 2 (SGLT2) inhibitors, HbA1c levels are higher than glycated albumin levels. This study therefore aimed to evaluate the discrepancy between HbA1c and glucose management indicator (GMI), an index of glucose management derived from continuous glucose monitoring, in this population.
Materials and Methods
This multicenter retrospective cohort study included patients with diabetes in whom HbA1c and GMI were simultaneously measured at two Japanese institutions. Data were collected when HbA1c levels had stabilized for at least 6 months after the administration of an oral hypoglycemic agent. The primary outcome was the discrepancy between HbA1c and GMI among patients receiving SGLT2 inhibitors and those receiving other oral hypoglycemic agents. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding factors.
Results
In total, 136 patients were included; of these, 109 and 27 were included in the SGLT2 inhibitor group and control group, respectively. After IPTW adjustment, the discrepancy between HbA1c and GMI (HbA1c–GMI) was significantly higher in the SGLT2 inhibitor group than in the control group (β = 0.42; 95% confidence interval 0.14–0.70; P = 0.003).
Conclusions
Patients receiving SGLT2 inhibitors may have increased HbA1c relative to their actual glycemic control.
{"title":"Increased HbA1c relative to actual glycemic control in patients treated with sodium–glucose cotransporter 2 inhibitors","authors":"Keigo Mizutani, Eita Uenishi, Takeshi Onoue, Ryutaro Maeda, Koji Suzuki, Tomoko Handa, Tomoko Kobayashi, Shintaro Iwama, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Masaki Okazaki, Atsushi Hashizume, Hiroshi Arima","doi":"10.1111/jdi.70191","DOIUrl":"10.1111/jdi.70191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Among patients with diabetes receiving sodium–glucose cotransporter 2 (SGLT2) inhibitors, HbA1c levels are higher than glycated albumin levels. This study therefore aimed to evaluate the discrepancy between HbA1c and glucose management indicator (GMI), an index of glucose management derived from continuous glucose monitoring, in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This multicenter retrospective cohort study included patients with diabetes in whom HbA1c and GMI were simultaneously measured at two Japanese institutions. Data were collected when HbA1c levels had stabilized for at least 6 months after the administration of an oral hypoglycemic agent. The primary outcome was the discrepancy between HbA1c and GMI among patients receiving SGLT2 inhibitors and those receiving other oral hypoglycemic agents. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 136 patients were included; of these, 109 and 27 were included in the SGLT2 inhibitor group and control group, respectively. After IPTW adjustment, the discrepancy between HbA1c and GMI (HbA1c–GMI) was significantly higher in the SGLT2 inhibitor group than in the control group (β = 0.42; 95% confidence interval 0.14–0.70; <i>P</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients receiving SGLT2 inhibitors may have increased HbA1c relative to their actual glycemic control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"34-41"},"PeriodicalIF":3.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511350","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}
This study aimed to investigate whether the use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) is associated with an increase in hemoglobin in the presence of chronic inflammation.
Materials and Methods
This is a matched-pair cohort study. Patients with diabetes who visited outpatient clinics from 2019 to 2023 were enrolled. New users and never-users of SGLT2is were matched by propensity scores, separately for those with C-reactive protein (CRP) levels lower than and higher than the median time-averaged CRP. Hemoglobin levels at the last visit for given estimated glomerular filtration rates (eGFR) were estimated using robust regression models with cubic terms of eGFR as covariates. Changes in hemoglobin, CRP, and mean corpuscular volume (MCV) were compared using mixed-effects models.
Results
Among 1835 never-users and 690 new users of SGLT2i, 209 and 127 pairs were matched for those with lower and higher time-averaged CRP, respectively. Hemoglobin levels at the last visit were higher among new SGLT2i users, irrespective of CRP levels (P for interaction 0.25). During the first 6 months, hemoglobin increased among new SGLT2i users while it decreased among never-users, and the difference in the trajectories of hemoglobin was more prominent among those with higher time-averaged CRP (P for 3-way interaction 0.02). CRP remained stable irrespective of SGLT2i use and MCV increased among SGLT2i users with higher CRP levels.
Conclusions
SGLT2i use was associated with an increase in hemoglobin levels irrespective of chronic inflammation.
{"title":"Chronic inflammation is not associated with attenuated sodium-glucose co-transporter 2 inhibitor-induced hemoglobin increase in patients with diabetes","authors":"Miho Murashima, Kodai Suzuki, Takahisa Kasugai, Yuki Miyaguchi, Maki Hiratsuka, Tatsuya Tomonari, Minamo Ono, Masashi Mizuno, Tomohiro Tanaka, Takayuki Hamano","doi":"10.1111/jdi.70189","DOIUrl":"10.1111/jdi.70189","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>This study aimed to investigate whether the use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) is associated with an increase in hemoglobin in the presence of chronic inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This is a matched-pair cohort study. Patients with diabetes who visited outpatient clinics from 2019 to 2023 were enrolled. New users and never-users of SGLT2is were matched by propensity scores, separately for those with C-reactive protein (CRP) levels lower than and higher than the median time-averaged CRP. Hemoglobin levels at the last visit for given estimated glomerular filtration rates (eGFR) were estimated using robust regression models with cubic terms of eGFR as covariates. Changes in hemoglobin, CRP, and mean corpuscular volume (MCV) were compared using mixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1835 never-users and 690 new users of SGLT2i, 209 and 127 pairs were matched for those with lower and higher time-averaged CRP, respectively. Hemoglobin levels at the last visit were higher among new SGLT2i users, irrespective of CRP levels (<i>P</i> for interaction 0.25). During the first 6 months, hemoglobin increased among new SGLT2i users while it decreased among never-users, and the difference in the trajectories of hemoglobin was more prominent among those with higher time-averaged CRP (<i>P</i> for 3-way interaction 0.02). CRP remained stable irrespective of SGLT2i use and MCV increased among SGLT2i users with higher CRP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SGLT2i use was associated with an increase in hemoglobin levels irrespective of chronic inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"25-33"},"PeriodicalIF":3.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145493871","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}
To develop and validate an early second-trimester predictive model integrating body mass index (BMI) trajectories and pathophysiological biomarkers for gestational diabetes mellitus (GDM) risk stratification, with the aim of reducing weight-monitoring frequency while maintaining predictive accuracy.
Methods
In this prospective dual-center cohort study, 1,450 pregnant women (<12 weeks gestation) without preexisting diabetes were enrolled from two Beijing maternal-child hospitals. Serial anthropometric (BMI at 6–10, 12–14, 15–19, and 24–28 weeks) and metabolic biomarkers (fasting glucose, C-peptide, lipids, uric acid) were analyzed. GDM was diagnosed via 75 g OGTT at 24–28 weeks. Multivariable logistic regression identified predictors using a 7:3 training-test split. Model performance was assessed by area under the ROC curve (AUC), calibration, and decision curve analysis.
Results
GDM incidence was 26.1% (378/1,450). Significant weight/BMI disparities emerged as early as 6–10 weeks (GDM vs NGT: +2.3 kg, P < 0.0001), escalating through gestation. The final model incorporated age (OR = 1.07/year, 95% CI = 1.03–1.11), 12–14-week BMI (OR = 1.06/kg/m2, 1.01–1.12), fasting glucose (OR = 1.86/mmol/L, 1.45–2.40), fasting C-peptide (OR = 1.87/ng/mL, 1.28–2.73). The model demonstrated moderate discrimination (training AUC = 0.684; testing AUC = 0.685) with 63.7–67.2% sensitivity and 59.8–61.4% specificity at the optimal threshold (0.237). Negative predictive values exceeded 82%, enabling effective risk exclusion.
Conclusions
This dual-center model pioneers GDM risk stratification by 12–14 weeks using clinically accessible metrics, reducing weight-monitoring frequency without compromising prognostic value. While AUC limitations (0.68–0.69) suggest unmeasured contributors, its operational simplicity and robust negative predictive capacity support implementation in resource-constrained settings. The findings redefine antenatal care paradigms by shifting focus to early metabolic dysregulation rather than late diagnostic thresholds.
{"title":"Dual-center prospective validation of an early second-trimester predictive model integrating BMI trajectories and pathophysiological biomarkers for gestational diabetes risk stratification","authors":"Junxiang Gao, Shuoning Song, Yanbei Duo, Xiaolin Qiao, Yuemei Zhang, Jiyu Xu, Jing Zhang, Xiaorui Nie, Qiujin Sun, Xianchun Yang, Ailing Wang, Wei Sun, Yong Fu, Mengmeng Zhang, Yingyue Dong, Zechun Lu, Tao Yuan, Weigang Zhao","doi":"10.1111/jdi.70179","DOIUrl":"10.1111/jdi.70179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop and validate an early second-trimester predictive model integrating body mass index (BMI) trajectories and pathophysiological biomarkers for gestational diabetes mellitus (GDM) risk stratification, with the aim of reducing weight-monitoring frequency while maintaining predictive accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective dual-center cohort study, 1,450 pregnant women (<12 weeks gestation) without preexisting diabetes were enrolled from two Beijing maternal-child hospitals. Serial anthropometric (BMI at 6–10, 12–14, 15–19, and 24–28 weeks) and metabolic biomarkers (fasting glucose, C-peptide, lipids, uric acid) were analyzed. GDM was diagnosed via 75 g OGTT at 24–28 weeks. Multivariable logistic regression identified predictors using a 7:3 training-test split. Model performance was assessed by area under the ROC curve (AUC), calibration, and decision curve analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GDM incidence was 26.1% (378/1,450). Significant weight/BMI disparities emerged as early as 6–10 weeks (GDM vs NGT: +2.3 kg, <i>P</i> < 0.0001), escalating through gestation. The final model incorporated age (OR = 1.07/year, 95% CI = 1.03–1.11), 12–14-week BMI (OR = 1.06/kg/m<sup>2</sup>, 1.01–1.12), fasting glucose (OR = 1.86/mmol/L, 1.45–2.40), fasting C-peptide (OR = 1.87/ng/mL, 1.28–2.73). The model demonstrated moderate discrimination (training AUC = 0.684; testing AUC = 0.685) with 63.7–67.2% sensitivity and 59.8–61.4% specificity at the optimal threshold (0.237). Negative predictive values exceeded 82%, enabling effective risk exclusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This dual-center model pioneers GDM risk stratification by 12–14 weeks using clinically accessible metrics, reducing weight-monitoring frequency without compromising prognostic value. While AUC limitations (0.68–0.69) suggest unmeasured contributors, its operational simplicity and robust negative predictive capacity support implementation in resource-constrained settings. The findings redefine antenatal care paradigms by shifting focus to early metabolic dysregulation rather than late diagnostic thresholds.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"150-164"},"PeriodicalIF":3.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501270","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}
Muscle wasting is common in heart failure (HF) patients, particularly those with diabetes mellitus (DM). Renin-angiotensin system inhibitors (RASI) may have muscle-protective effects, but their association with muscle wasting in diabetic HF patients remains unclear. We investigated whether the association between RASI use and muscle wasting differs by DM status and plasma 3-methylhistidine (3-Me-His) levels, a muscle protein breakdown biomarker.
Materials and Methods
We performed a cross-sectional analysis of 384 hospitalized HF patients (mean age 71 ± 14 years, 41% female, 38% with DM). Muscle wasting was defined by dual-energy X-ray absorptiometry according to the Asian Working Group for Sarcopenia criteria. Associations between RASI use and muscle wasting were evaluated using logistic regression with inverse probability of treatment weighting. Interaction analyses assessed effect modification by DM status and 3-Me-His levels.
Results
Muscle wasting prevalence was 58%. DM was an independent risk factor for muscle wasting (adjusted odds ratio [OR] 2.07, 95% confidence interval [CI] 1.27–3.38, P = 0.004). RASI were prescribed in 52% of patients. After adjustment, a significant interaction with DM was observed (P = 0.033). Among DM patients, RASI use was associated with lower muscle wasting (OR 0.33, 95% CI 0.14–0.76, P = 0.010), while no association was found in non-DM patients. Within the DM subgroup, the association was more evident in patients with lower 3-Me-His levels (OR 0.12, 95% CI 0.03–0.52, P = 0.005).
Conclusions
RASI use was associated with significantly lower muscle wasting in HF patients with DM, particularly those with lower 3-Me-His levels. These findings suggest a potential therapeutic window and warrant prospective investigation.
目的：肌肉萎缩在心力衰竭（HF）患者中很常见，尤其是糖尿病（DM）患者。肾素-血管紧张素系统抑制剂（RASI）可能具有肌肉保护作用，但其与糖尿病心衰患者肌肉萎缩的关系尚不清楚。我们研究了RASI使用与肌肉萎缩之间的关系是否因糖尿病状态和血浆3-甲基组氨酸（3-Me-His）水平（一种肌肉蛋白分解生物标志物）而异。材料和方法：我们对384例住院HF患者（平均年龄71±14岁，女性41%，糖尿病38%）进行了横断面分析。根据亚洲肌少症工作组的标准，用双能x线吸收测定法定义肌肉萎缩。使用RASI和肌肉萎缩之间的关系使用治疗加权逆概率的逻辑回归进行评估。交互作用分析评估DM状态和3-Me-His水平对效果的影响。结果：肌肉萎缩率为58%。DM是肌肉萎缩的独立危险因素（校正优势比[OR] 2.07, 95%可信区间[CI] 1.27 ~ 3.38, P = 0.004）。52%的患者使用RASI。调整后，与DM有显著交互作用（P = 0.033）。在糖尿病患者中，RASI的使用与较低的肌肉萎缩相关（OR 0.33, 95% CI 0.14-0.76, P = 0.010），而在非糖尿病患者中没有发现关联。在糖尿病亚组中，3-Me-His水平较低的患者的相关性更为明显（OR 0.12, 95% CI 0.03-0.52, P = 0.005）。结论：使用RASI可显著降低合并DM的HF患者的肌肉萎缩，特别是那些3-Me-His水平较低的患者。这些发现提示了一个潜在的治疗窗口，值得进行前瞻性研究。
{"title":"Protective association of renin-angiotensin system inhibitor use with skeletal muscle wasting in diabetic heart failure","authors":"Hidemichi Kouzu, Toshiyuki Yano, Satoshi Katano, Wataru Kawaharata, Ryo Numazawa, Ryohei Nagaoka, Hiroki Aida, Katsuhiko Ohori, Takefumi Fujito, Nobutaka Nagano, Masato Furuhashi","doi":"10.1111/jdi.70186","DOIUrl":"10.1111/jdi.70186","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Muscle wasting is common in heart failure (HF) patients, particularly those with diabetes mellitus (DM). Renin-angiotensin system inhibitors (RASI) may have muscle-protective effects, but their association with muscle wasting in diabetic HF patients remains unclear. We investigated whether the association between RASI use and muscle wasting differs by DM status and plasma 3-methylhistidine (3-Me-His) levels, a muscle protein breakdown biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional analysis of 384 hospitalized HF patients (mean age 71 ± 14 years, 41% female, 38% with DM). Muscle wasting was defined by dual-energy X-ray absorptiometry according to the Asian Working Group for Sarcopenia criteria. Associations between RASI use and muscle wasting were evaluated using logistic regression with inverse probability of treatment weighting. Interaction analyses assessed effect modification by DM status and 3-Me-His levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Muscle wasting prevalence was 58%. DM was an independent risk factor for muscle wasting (adjusted odds ratio [OR] 2.07, 95% confidence interval [CI] 1.27–3.38, <i>P</i> = 0.004). RASI were prescribed in 52% of patients. After adjustment, a significant interaction with DM was observed (<i>P</i> = 0.033). Among DM patients, RASI use was associated with lower muscle wasting (OR 0.33, 95% CI 0.14–0.76, <i>P</i> = 0.010), while no association was found in non-DM patients. Within the DM subgroup, the association was more evident in patients with lower 3-Me-His levels (OR 0.12, 95% CI 0.03–0.52, <i>P</i> = 0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>RASI use was associated with significantly lower muscle wasting in HF patients with DM, particularly those with lower 3-Me-His levels. These findings suggest a potential therapeutic window and warrant prospective investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"73-82"},"PeriodicalIF":3.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494025","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}
Sen Cai, Lingtao Xu, Shaole Wan, Zengyong Hu, Yonghui Shen
Background
Diabetic foot ulcers (DFU) have become a global health issue. Chronic inflammation is a key pathological feature of DFU; however, its role in the diagnosis of DFU remains unclear.
Methods
DFU sample data were acquired from public databases, and weighted gene co-expression network analysis (WGCNA) was employed to identify key genes associated with DFU traits. A protein–protein interaction (PPI) network was constructed to screen for diagnostic biomarkers, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy of these key genes. The non-negative matrix factorization algorithm was applied to classify DFU samples. To further investigate the potential molecular mechanisms of these diagnostic genes, single-gene functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA) for immune infiltration, and construction of upstream transcription factor regulatory networks were conducted.
Results
Four feature genes (FOSL1, HBEGF, S100A12, and TICAM1) demonstrating diagnostic potential were identified. ROC curve analysis validated these genes as potential diagnostic biomarkers for DFU. Functional enrichment analysis indicated that these genes are predominantly involved in biological processes related to keratinization and differentiation of epidermal skin cells. Furthermore, the expression levels of these feature genes exhibited a significant negative correlation with the infiltration levels of most immune cells. The regulatory network of upstream transcription factors highlighted the interconnectedness of these feature genes.
Conclusion
This study identified DFU diagnostic genes linked to the inflammatory response, revealing their distinct transcriptional profiles and functional enrichment. These discoveries advance understanding of DFU pathology and provide a theoretical foundation for early diagnosis and treatment.
{"title":"Identification and validation of novel inflammatory response-related diagnostic biomarkers in diabetic foot ulcers","authors":"Sen Cai, Lingtao Xu, Shaole Wan, Zengyong Hu, Yonghui Shen","doi":"10.1111/jdi.70164","DOIUrl":"10.1111/jdi.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic foot ulcers (DFU) have become a global health issue. Chronic inflammation is a key pathological feature of DFU; however, its role in the diagnosis of DFU remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DFU sample data were acquired from public databases, and weighted gene co-expression network analysis (WGCNA) was employed to identify key genes associated with DFU traits. A protein–protein interaction (PPI) network was constructed to screen for diagnostic biomarkers, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy of these key genes. The non-negative matrix factorization algorithm was applied to classify DFU samples. To further investigate the potential molecular mechanisms of these diagnostic genes, single-gene functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA) for immune infiltration, and construction of upstream transcription factor regulatory networks were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four feature genes (FOSL1, HBEGF, S100A12, and TICAM1) demonstrating diagnostic potential were identified. ROC curve analysis validated these genes as potential diagnostic biomarkers for DFU. Functional enrichment analysis indicated that these genes are predominantly involved in biological processes related to keratinization and differentiation of epidermal skin cells. Furthermore, the expression levels of these feature genes exhibited a significant negative correlation with the infiltration levels of most immune cells. The regulatory network of upstream transcription factors highlighted the interconnectedness of these feature genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified DFU diagnostic genes linked to the inflammatory response, revealing their distinct transcriptional profiles and functional enrichment. These discoveries advance understanding of DFU pathology and provide a theoretical foundation for early diagnosis and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"103-119"},"PeriodicalIF":3.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457329","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}
Hong-ping Gong, Yan Ren, Thet Htar Swe, Zhen-yi Li, Pan-pan Zha, Da-wei Chen, Xing-wu Ran, Chun Wang
Objective
Diabetic foot ulcers (DFUs) have increasingly affected younger populations. This study aimed to analyze the clinical characteristics of DFUs in different age groups of diabetic patients with foot ulcers.
Methods
This is a retrospective cohort study of diabetic patients with foot ulcers admitted to West China Hospital, Sichuan University. They were divided into the young (<45 years), the middle-aged (45–64 years), and the elderly groups (≥65 years). The patients were followed up for a median of 44.5 months, either at the outpatient department or by phone.
Results
This study enrolled 1,209 patients with DFUs, stratified into three groups according to age: young (n = 65), middle-aged (n = 509), and elderly (n = 635). All patients had a long history of diabetes with an average duration of 11.5 years. The DFU patients of all ages have poor glycemic control. About one-third of the patients have recurrent foot ulcers. The prevalence of comorbidities such as hypertension, coronary artery disease, chronic kidney disease, and peripheral artery disease increased significantly with age (P < 0.001). Neuropathic foot ulcers were more common in the young patients (48.3%), whereas neuro-ischemic ulcers were more prevalent in the middle-aged (42.1%) and elderly patients (56.9%). Compared with the young (27.7%) and middle-aged patients (26.9%), the ulcer healing rates during hospitalization were significantly lower in the elderly patients (18.9%, P = 0.004). During a median 44.5 (IQR 18.7–74.5)-month follow-up period, 375 (36.2%) deaths occurred, and all-cause mortality increased significantly with age (P < 0.001).
Conclusion
Clinical characteristics of DFUs are profoundly age-dependent: younger patients exhibited poorer glycemic control, neuropathic ulcers, and mechanical injuries, while the older patients developed more vascular complications and neuro-ischemic ulcers. Therefore, different prevention and treatment measures should be taken for DFUs based on their clinical characteristics in different age groups.
{"title":"Age-related variations in clinical characteristics of patients with diabetic foot ulcers","authors":"Hong-ping Gong, Yan Ren, Thet Htar Swe, Zhen-yi Li, Pan-pan Zha, Da-wei Chen, Xing-wu Ran, Chun Wang","doi":"10.1111/jdi.70181","DOIUrl":"10.1111/jdi.70181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Diabetic foot ulcers (DFUs) have increasingly affected younger populations. This study aimed to analyze the clinical characteristics of DFUs in different age groups of diabetic patients with foot ulcers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a retrospective cohort study of diabetic patients with foot ulcers admitted to West China Hospital, Sichuan University. They were divided into the young (<45 years), the middle-aged (45–64 years), and the elderly groups (≥65 years). The patients were followed up for a median of 44.5 months, either at the outpatient department or by phone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study enrolled 1,209 patients with DFUs, stratified into three groups according to age: young (<i>n</i> = 65), middle-aged (<i>n</i> = 509), and elderly (<i>n</i> = 635). All patients had a long history of diabetes with an average duration of 11.5 years. The DFU patients of all ages have poor glycemic control. About one-third of the patients have recurrent foot ulcers. The prevalence of comorbidities such as hypertension, coronary artery disease, chronic kidney disease, and peripheral artery disease increased significantly with age (<i>P</i> < 0.001). Neuropathic foot ulcers were more common in the young patients (48.3%), whereas neuro-ischemic ulcers were more prevalent in the middle-aged (42.1%) and elderly patients (56.9%). Compared with the young (27.7%) and middle-aged patients (26.9%), the ulcer healing rates during hospitalization were significantly lower in the elderly patients (18.9%, <i>P</i> = 0.004). During a median 44.5 (IQR 18.7–74.5)-month follow-up period, 375 (36.2%) deaths occurred, and all-cause mortality increased significantly with age (<i>P</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Clinical characteristics of DFUs are profoundly age-dependent: younger patients exhibited poorer glycemic control, neuropathic ulcers, and mechanical injuries, while the older patients developed more vascular complications and neuro-ischemic ulcers. Therefore, different prevention and treatment measures should be taken for DFUs based on their clinical characteristics in different age groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"96-102"},"PeriodicalIF":3.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443661","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}
<p>The therapeutic journey of sodium–glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes reflects a remarkable transformation in clinical medicine. When these agents were first introduced more than a decade ago, skepticism prevailed. Their mechanism of action, independent of pancreatic β-cell stimulation, raised doubts about the durability of glycemic efficacy. Safety concerns were also voiced, particularly regarding dehydration, genitourinary infections, and the possibility of euglycemic diabetic ketoacidosis. Moreover, some speculated that metabolic change might lead to impaired amino acid utilization, muscle catabolism, and sarcopenia in vulnerable patients. Over 10 years later, however, most of these initial fears have been largely dispelled: with appropriate use, SGLT2 inhibitors have proven to provide durable glucose lowering together with systemic benefits. Experimental studies have also demonstrated protective effects on pancreatic β cells, suggesting that SGLT2 inhibition may contribute to the preservation of endogenous insulin secretion capacity<span><sup>1</sup></span>. What was once regarded as a controversial class of glucose-lowering drugs is now widely recognized as a cornerstone of diabetes management, offering multi-organ protection that extends to the cardiovascular, renal, hepatic, and even neurological systems (Figure 1).</p><p>A line of evidence has reduced safety concerns. Long-term observational data from East Asia demonstrated that the overall incidence of adverse events with SGLT2 inhibition was below 5% even in older patients<span><sup>2</sup></span>. A large prospective multicenter study in Japan reported that adverse events were mainly limited to mild or moderate urinary/genital infections and volume depletion, and importantly, unexpected serious safety signals were observed<span><sup>3</sup></span>.</p><p>A recent systematic review and meta-analysis with over 77,000 older or frail patients with type 2 diabetes and heart failure demonstrated that SGLT2 inhibitor therapy was associated with an approximately 20% reduction in all-cause mortality and a 30% reduction in hospitalization for heart failure<span><sup>4</sup></span>. These findings suggest that SGLT2 inhibitors consistently lower the risk of death and heart failure hospitalization even in frail or older individuals with type 2 diabetes.</p><p>In a large 3-year post-marketing surveillance study conducted in Japan, empagliflozin was well tolerated across a broad age range, with no major new safety concerns identified<span><sup>5</sup></span>. The magnitude of weight reduction varied by baseline body mass index (BMI): the greatest decrease was observed in patients with BMI ≥30 kg/m<sup>2</sup>, whereas almost no change was seen in patients with BMI <20 kg/m<sup>2</sup>. These findings suggest that SGLT2 inhibitors are generally safe and effective even in lean and elderly patients.</p><p>An interesting analysis using the Japan Medical Data Center (JMDC)
restore -肾病研究表明，tofogliflozin可减少2型糖尿病和糖尿病肾病患者的尿白蛋白排泄并改善肝酶。值得注意的是，尿白蛋白水平在治疗期间下降，停药后上升，再次给药后再次下降，突出了其肾保护作用的可逆性和持续治疗的重要性。除了保护肾脏，微血管对眼睛的影响现在也被认识到。在一项来自日本的全国范围的数据分析中，包括2412名倾向评分匹配的糖尿病性黄斑水肿患者，SGLT2抑制剂治疗显著降低了玻璃体内注射曲安奈德的需求，发病率为63.8 vs 94.9 / 1000人年，重复注射的风险比为0.66-0.44 13。因此，SGLT2抑制剂可能作为一种新的、低成本的辅助选择治疗糖尿病黄斑水肿。也许，最令人兴奋的前沿涉及认知。在一项以人群为基础的2型糖尿病老年人回顾性队列研究中，根据倾向评分加权Cox模型，与DPP-4抑制剂相比，开始使用SGLT2抑制剂可使痴呆发生风险降低约20% （aHR 0.80）。使用孟德尔随机化的遗传学研究也支持SGLT2抑制的神经保护作用，将遗传代理抑制与长寿、更好的认知和衰老的大脑结构标志物联系起来。一项前瞻性队列研究表明，henagliflozin可显著改善2型糖尿病合并认知功能障碍患者的蒙特利尔认知评估（MoCA）评分，降低血浆p-tau181水平，且独立于血糖控制16。这些结果突出了SGLT2抑制剂将其器官保护功能扩展到大脑的潜力。综合这些不同的发现，SGLT2抑制剂显然已经超越了它们最初作为降血糖药物的作用。它们现在被广泛认为是系统性器官保护疗法，在心血管、肾脏、肝脏、眼科和神经系统领域都有益处。然而，重要的差距仍然存在。老年体弱伴肌肉减少症、认知障碍或功能依赖的证据仍然有限。虽然早期数据很有希望，但需要专门的大规模随机对照试验和微血管和神经保护途径的机制研究。最后，联合方法，特别是GLP-1受体激动剂，代表了协同器官保护的一个令人兴奋的前沿。总之，经过十多年的临床使用，早期的担忧已经被安全性和多器官益处的一致证据所取代。综上所述，来自众多研究的发现表明SGLT2抑制剂是一种变革性疗法，能够在人口老龄化时代重塑糖尿病护理，在这个时代，系统性保护越来越重要。曾担任诺和诺德制药、三和鹿歌制药、大正制药、住友制药、三菱田边制药、日本勃林格殷格翰制药等公司的顾问，并获得讲座奖金和奖学金。数据共享不适用于本文，因为在当前研究期间没有生成或分析数据集。
{"title":"A decade of SGLT2 inhibitors: Lessons learned and the road ahead in type 2 diabetes","authors":"Tomohiko Kimura, Kohei Kaku","doi":"10.1111/jdi.70187","DOIUrl":"10.1111/jdi.70187","url":null,"abstract":"<p>The therapeutic journey of sodium–glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes reflects a remarkable transformation in clinical medicine. When these agents were first introduced more than a decade ago, skepticism prevailed. Their mechanism of action, independent of pancreatic β-cell stimulation, raised doubts about the durability of glycemic efficacy. Safety concerns were also voiced, particularly regarding dehydration, genitourinary infections, and the possibility of euglycemic diabetic ketoacidosis. Moreover, some speculated that metabolic change might lead to impaired amino acid utilization, muscle catabolism, and sarcopenia in vulnerable patients. Over 10 years later, however, most of these initial fears have been largely dispelled: with appropriate use, SGLT2 inhibitors have proven to provide durable glucose lowering together with systemic benefits. Experimental studies have also demonstrated protective effects on pancreatic β cells, suggesting that SGLT2 inhibition may contribute to the preservation of endogenous insulin secretion capacity<span><sup>1</sup></span>. What was once regarded as a controversial class of glucose-lowering drugs is now widely recognized as a cornerstone of diabetes management, offering multi-organ protection that extends to the cardiovascular, renal, hepatic, and even neurological systems (Figure 1).</p><p>A line of evidence has reduced safety concerns. Long-term observational data from East Asia demonstrated that the overall incidence of adverse events with SGLT2 inhibition was below 5% even in older patients<span><sup>2</sup></span>. A large prospective multicenter study in Japan reported that adverse events were mainly limited to mild or moderate urinary/genital infections and volume depletion, and importantly, unexpected serious safety signals were observed<span><sup>3</sup></span>.</p><p>A recent systematic review and meta-analysis with over 77,000 older or frail patients with type 2 diabetes and heart failure demonstrated that SGLT2 inhibitor therapy was associated with an approximately 20% reduction in all-cause mortality and a 30% reduction in hospitalization for heart failure<span><sup>4</sup></span>. These findings suggest that SGLT2 inhibitors consistently lower the risk of death and heart failure hospitalization even in frail or older individuals with type 2 diabetes.</p><p>In a large 3-year post-marketing surveillance study conducted in Japan, empagliflozin was well tolerated across a broad age range, with no major new safety concerns identified<span><sup>5</sup></span>. The magnitude of weight reduction varied by baseline body mass index (BMI): the greatest decrease was observed in patients with BMI ≥30 kg/m<sup>2</sup>, whereas almost no change was seen in patients with BMI <20 kg/m<sup>2</sup>. These findings suggest that SGLT2 inhibitors are generally safe and effective even in lean and elderly patients.</p><p>An interesting analysis using the Japan Medical Data Center (JMDC)","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2142-2144"},"PeriodicalIF":3.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407700","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}
Middle-aged and elderly individuals in Asia with type 2 diabetes mellitus have an increased risk of developing sarcopenia. This systematic review and meta-analysis aimed to estimate sarcopenia prevalence and identify key risk factors among middle-aged and elderly type 2 diabetes mellitus persons in Asia.
Materials and Methods
We searched PubMed, Embase, Cochrane Library, Web of Science, and CINAHL up to August 2025. Observational studies on persons aged ≥45 with type 2 diabetes mellitus reporting sarcopenia prevalence and risk factors were included. Quality was assessed using the Newcastle–Ottawa Scale, and random-effects models calculated pooled estimates.
Results
A total of 43 studies with sarcopenia prevalence in type 2 diabetes mellitus ranging from 4.0% to 50.0% were included. The pooled prevalence among individuals with type 2 diabetes mellitus was 17 (14–21%), 13 (8–18%), and 17% (14–21%) for overall, middle-aged, and elderly individuals, respectively, with no significant difference between the middle-aged and elderly individuals. Sarcopenia was higher in Southeast Asia (28%). Key risk factors included advanced age (OR = 1.12), elevated HbA1c (OR = 1.11), diabetes-related complications (nephropathy OR = 1.76 and neuropathy OR = 3.28), and a higher body fat percentage in men (OR = 1.26) and women (OR = 1.27). In contrast, protective factors included a higher BMI (OR = 0.66), a better Mini Nutritional Assessment score (OR = 0.37), and the use of metformin (OR = 0.26).
Conclusions
Sarcopenia is common in middle-aged and older Asian adults with type 2 diabetes mellitus. Interventions targeting glycemic control, complications, body composition, nutrition, and metformin may help reduce risk. This study highlights the importance of early sarcopenia screening and prevention, especially in middle-aged individuals with type 2 diabetes mellitus. Further studies are needed to establish causal relationships for prevention.
{"title":"Prevalence and risk factors of sarcopenia in Asian adults with type 2 diabetes: A systematic review and meta-analysis","authors":"Yueh-Chu Wu, Man-Ting Mao, Hung-En Huang, Chien-Ning Huang, Wen-Chun Liao","doi":"10.1111/jdi.70185","DOIUrl":"10.1111/jdi.70185","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Middle-aged and elderly individuals in Asia with type 2 diabetes mellitus have an increased risk of developing sarcopenia. This systematic review and meta-analysis aimed to estimate sarcopenia prevalence and identify key risk factors among middle-aged and elderly type 2 diabetes mellitus persons in Asia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We searched PubMed, Embase, Cochrane Library, Web of Science, and CINAHL up to August 2025. Observational studies on persons aged ≥45 with type 2 diabetes mellitus reporting sarcopenia prevalence and risk factors were included. Quality was assessed using the Newcastle–Ottawa Scale, and random-effects models calculated pooled estimates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 43 studies with sarcopenia prevalence in type 2 diabetes mellitus ranging from 4.0% to 50.0% were included. The pooled prevalence among individuals with type 2 diabetes mellitus was 17 (14–21%), 13 (8–18%), and 17% (14–21%) for overall, middle-aged, and elderly individuals, respectively, with no significant difference between the middle-aged and elderly individuals. Sarcopenia was higher in Southeast Asia (28%). Key risk factors included advanced age (OR = 1.12), elevated HbA<sub>1c</sub> (OR = 1.11), diabetes-related complications (nephropathy OR = 1.76 and neuropathy OR = 3.28), and a higher body fat percentage in men (OR = 1.26) and women (OR = 1.27). In contrast, protective factors included a higher BMI (OR = 0.66), a better Mini Nutritional Assessment score (OR = 0.37), and the use of metformin (OR = 0.26).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sarcopenia is common in middle-aged and older Asian adults with type 2 diabetes mellitus. Interventions targeting glycemic control, complications, body composition, nutrition, and metformin may help reduce risk. This study highlights the importance of early sarcopenia screening and prevention, especially in middle-aged individuals with type 2 diabetes mellitus. Further studies are needed to establish causal relationships for prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"83-95"},"PeriodicalIF":3.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399396","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}
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