Investigate the impact and mechanism of semaglutide (Sema) combined with high-intensity interval training (HIIT) on hepatic glucose/lipid metabolism in db/db mice using untargeted metabolomics.
Methods
Db/db mice were divided into model control, Sema alone, and Sema + HIIT groups, with db/m mice as controls. Sema (0.1 mg/kg/week) was administered subcutaneously, and the control group was subcutaneously injected with the same volume of distilled water. Engaging in HIIT swimming occurred for five consecutive days weekly. Weekly fasting plasma glucose (FPG), body mass, and food intake were assessed. After 8 weeks, blood/liver tissues were analyzed; liver metabolomics used LC–MS.
Results
Following an 8-week intervention, it was determined that the weight loss efficacy of Sema alone was suboptimal. The lowering of FPG did not differ significantly between the Sema alone and the combined intervention groups. The combined treatment demonstrated superior efficacy compared with Sema alone in enhancing liver weight, liver index, food intake, TG, TC, hepatic TG, and liver injury biomarkers (AST, ALT; P < 0.05). Histological findings indicated that the combination intervention markedly decreased fat vacuoles and inflammatory infiltration in hepatocytes (P < 0.001). A total of 721 differential metabolites were identified after the combined intervention, with primary alterations in amino acids and their derivatives, lipids, energy metabolism, and bile acids, encompassing key pathways such as the TCA cycle, amino acid metabolism, and bile acid metabolism.
Conclusions
Semaglutide combined with HIIT synergistically improves hepatic glucose and lipid metabolism in diabetic mice, providing a new treatment strategy for liver lipid disorders.
{"title":"Multi-pathway-driven hepatic protection: Semaglutide combined with HIIT counteracts diabetic liver injury in db/db mice","authors":"Wenjun Yu, Yongfu Liu, Shenglong Le, Yuxin Xiao, Xiaoyan Chen, Junhua Wang, Feng Gao","doi":"10.1111/jdi.70174","DOIUrl":"10.1111/jdi.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Investigate the impact and mechanism of semaglutide (Sema) combined with high-intensity interval training (HIIT) on hepatic glucose/lipid metabolism in db/db mice using untargeted metabolomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Db/db mice were divided into model control, Sema alone, and Sema + HIIT groups, with db/m mice as controls. Sema (0.1 mg/kg/week) was administered subcutaneously, and the control group was subcutaneously injected with the same volume of distilled water. Engaging in HIIT swimming occurred for five consecutive days weekly. Weekly fasting plasma glucose (FPG), body mass, and food intake were assessed. After 8 weeks, blood/liver tissues were analyzed; liver metabolomics used LC–MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following an 8-week intervention, it was determined that the weight loss efficacy of Sema alone was suboptimal. The lowering of FPG did not differ significantly between the Sema alone and the combined intervention groups. The combined treatment demonstrated superior efficacy compared with Sema alone in enhancing liver weight, liver index, food intake, TG, TC, hepatic TG, and liver injury biomarkers (AST, ALT; <i>P</i> < 0.05). Histological findings indicated that the combination intervention markedly decreased fat vacuoles and inflammatory infiltration in hepatocytes (<i>P</i> < 0.001). A total of 721 differential metabolites were identified after the combined intervention, with primary alterations in amino acids and their derivatives, lipids, energy metabolism, and bile acids, encompassing key pathways such as the TCA cycle, amino acid metabolism, and bile acid metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Semaglutide combined with HIIT synergistically improves hepatic glucose and lipid metabolism in diabetic mice, providing a new treatment strategy for liver lipid disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2145-2159"},"PeriodicalIF":3.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249180","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}
I read with great interest the article by Luo et al., ‘Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism’1. The authors are to be commended for exploring the relatively underinvestigated role of mitochondrial genomic variation in gestational diabetes mellitus (GDM). Their large sample size and combined analysis of genetic variants and copy number are clear strengths.
However, addressing certain methodological considerations could further strengthen the robustness of the study findings. First, the case–control design, as an observational study, restricts causal inference. The associations observed between mtDNA variants and GDM may reflect secondary effects of pregnancy-related metabolic stress rather than primary causes2.
Second, the study was limited to a single Chinese cohort. Because mitochondrial haplogroup distribution differs across ethnic groups, the generalizability of the findings to other populations may be limited3.
Furthermore, the analysis focused largely on the mtDNA D-loop, without a comprehensive evaluation of heteroplasmy or coding region variants. Heteroplasmy, in particular, can significantly influence mitochondrial function, and overlooking it may provide an incomplete picture4.
In conclusion, Luo et al. have made an important contribution linking mitochondrial variation to GDM, and their findings open promising avenues for future research. Future studies incorporating longitudinal follow-up, multi-ethnic cohorts, and full mitochondrial genome sequencing with functional validation would be valuable to advance understanding in this field.
None.
The authors declare no conflict of interest.
Approval of the research protocol: None.
Informed consent: None.
Registry and registration no. of the study/trial: None.
Animal studies: None.
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
{"title":"Letter to editor in response to ‘Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism’","authors":"Ameer Ahmed, Sajida Parveen","doi":"10.1111/jdi.70177","DOIUrl":"10.1111/jdi.70177","url":null,"abstract":"<p>Dear Editor,</p><p>I read with great interest the article by Luo <i>et al</i>., ‘Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism’<span><sup>1</sup></span>. The authors are to be commended for exploring the relatively underinvestigated role of mitochondrial genomic variation in gestational diabetes mellitus (GDM). Their large sample size and combined analysis of genetic variants and copy number are clear strengths.</p><p>However, addressing certain methodological considerations could further strengthen the robustness of the study findings. First, the case–control design, as an observational study, restricts causal inference. The associations observed between mtDNA variants and GDM may reflect secondary effects of pregnancy-related metabolic stress rather than primary causes<span><sup>2</sup></span>.</p><p>Second, the study was limited to a single Chinese cohort. Because mitochondrial haplogroup distribution differs across ethnic groups, the generalizability of the findings to other populations may be limited<span><sup>3</sup></span>.</p><p>Furthermore, the analysis focused largely on the mtDNA D-loop, without a comprehensive evaluation of heteroplasmy or coding region variants. Heteroplasmy, in particular, can significantly influence mitochondrial function, and overlooking it may provide an incomplete picture<span><sup>4</sup></span>.</p><p>In conclusion, Luo <i>et al</i>. have made an important contribution linking mitochondrial variation to GDM, and their findings open promising avenues for future research. Future studies incorporating longitudinal follow-up, multi-ethnic cohorts, and full mitochondrial genome sequencing with functional validation would be valuable to advance understanding in this field.</p><p>None.</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 no. of the study/trial: 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":"16 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237446","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>Multiple large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have robustly shown that GLP-1 RAs lower the risk of major adverse cardiovascular events (MACE) in people with type 2 diabetes. Yet, two important knowledge gaps remain. First, previous CVOTs were dominated by injectable agents, leaving uncertainty about whether once-daily oral GLP-1 RAs confer comparable protection. Second, kidney benefits were inferred almost entirely from secondary endpoints of cardiovascular trials rather than from a kidney-specific outcomes study.</p><p>The latest meta-analysis published by Lee <i>et al</i>.<span><sup>1</sup></span> in <i>Diabetes Care</i> in 2025 presents the largest meta-analysis to date of cardiovascular and kidney outcomes with long-acting injectable and oral GLP-1 RAs in type 2 diabetes. Their study pools 10 trials (<i>n</i> = 71,351) and incorporates both the SOUL cardiovascular-outcome trial of oral semaglutide<span><sup>2</sup></span>- and the FLOW kidney-outcome trial of once-weekly semaglutide<span><sup>3</sup></span> (Table 1). In the meta-analysis, across a median 3.2-year follow-up, long-acting GLP-1 RAs reduced three-point MACE by 14% (HR 0.86), hospitalization for heart failure by 14%, composite kidney events by 17%, and all-cause mortality by 12%, without new safety concerns.</p><p>Earlier meta-analyses were dominated by injectable agents, leaving uncertainty over whether once-daily oral semaglutide could match them. Lee <i>et al</i>.<span><sup>1</sup></span> found no heterogeneity across administration routes for any efficacy endpoint (between-group heterogeneity <i>P</i> = 0.984). This underscores the potential of oral GLP-1 RA therapy to deliver clinical ‘hard outcome’ benefits comparable with injectables, allowing treatment to be tailored to individual preference.</p><p>However, the study also highlighted a permanent discontinuation rate of 25% in FLOW (injectable) and 27% in SOUL (oral). Discontinuation is influenced by patient preference, administration route, dosing frequency, convenience, and complexity, among other factors. Because oral semaglutide must be taken on an empty stomach with a small sip of water and followed by a 30-min fast, clinicians need to counsel patients carefully to optimize adherence.</p><p>FLOW, the first GLP-1 RA trial that used a hard kidney endpoint as its primary outcome, showed a 24% risk reduction in kidney failure–centric events alongside an 18% reduction in MACE. Pooled with the other trials, the class achieved a 17% reduction in composite kidney outcomes, reinforcing GLP-1 RAs as renoprotective agents.</p><p>The meta-analysis detected no increase in severe hypoglycemia, diabetic retinopathy, pancreatitis, or selected cancers versus placebo, consistent with prior safety reports.</p><p>Effect sizes mirror those of earlier meta-analysis with fewer individuals or the one that includes SELECT trial<span><sup>4</sup></span>, a CVOT of semaglutide i
{"title":"Cardiovascular and kidney benefits of GLP-1 receptor agonists across large randomized placebo-controlled trials","authors":"Satoshi Yoshiji, Nobuya Inagaki","doi":"10.1111/jdi.70166","DOIUrl":"10.1111/jdi.70166","url":null,"abstract":"<p>Multiple large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have robustly shown that GLP-1 RAs lower the risk of major adverse cardiovascular events (MACE) in people with type 2 diabetes. Yet, two important knowledge gaps remain. First, previous CVOTs were dominated by injectable agents, leaving uncertainty about whether once-daily oral GLP-1 RAs confer comparable protection. Second, kidney benefits were inferred almost entirely from secondary endpoints of cardiovascular trials rather than from a kidney-specific outcomes study.</p><p>The latest meta-analysis published by Lee <i>et al</i>.<span><sup>1</sup></span> in <i>Diabetes Care</i> in 2025 presents the largest meta-analysis to date of cardiovascular and kidney outcomes with long-acting injectable and oral GLP-1 RAs in type 2 diabetes. Their study pools 10 trials (<i>n</i> = 71,351) and incorporates both the SOUL cardiovascular-outcome trial of oral semaglutide<span><sup>2</sup></span>- and the FLOW kidney-outcome trial of once-weekly semaglutide<span><sup>3</sup></span> (Table 1). In the meta-analysis, across a median 3.2-year follow-up, long-acting GLP-1 RAs reduced three-point MACE by 14% (HR 0.86), hospitalization for heart failure by 14%, composite kidney events by 17%, and all-cause mortality by 12%, without new safety concerns.</p><p>Earlier meta-analyses were dominated by injectable agents, leaving uncertainty over whether once-daily oral semaglutide could match them. Lee <i>et al</i>.<span><sup>1</sup></span> found no heterogeneity across administration routes for any efficacy endpoint (between-group heterogeneity <i>P</i> = 0.984). This underscores the potential of oral GLP-1 RA therapy to deliver clinical ‘hard outcome’ benefits comparable with injectables, allowing treatment to be tailored to individual preference.</p><p>However, the study also highlighted a permanent discontinuation rate of 25% in FLOW (injectable) and 27% in SOUL (oral). Discontinuation is influenced by patient preference, administration route, dosing frequency, convenience, and complexity, among other factors. Because oral semaglutide must be taken on an empty stomach with a small sip of water and followed by a 30-min fast, clinicians need to counsel patients carefully to optimize adherence.</p><p>FLOW, the first GLP-1 RA trial that used a hard kidney endpoint as its primary outcome, showed a 24% risk reduction in kidney failure–centric events alongside an 18% reduction in MACE. Pooled with the other trials, the class achieved a 17% reduction in composite kidney outcomes, reinforcing GLP-1 RAs as renoprotective agents.</p><p>The meta-analysis detected no increase in severe hypoglycemia, diabetic retinopathy, pancreatitis, or selected cancers versus placebo, consistent with prior safety reports.</p><p>Effect sizes mirror those of earlier meta-analysis with fewer individuals or the one that includes SELECT trial<span><sup>4</sup></span>, a CVOT of semaglutide i","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2140-2141"},"PeriodicalIF":3.0,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231186","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}
It is well-known that when pancreatic β-cells are chronically exposed to hyperglycemia under diabetic conditions, β-cell function is gradually deteriorating. Although such phenomena were well-known as β-cell glucose toxicity in clinical practice, its molecular mechanism remained unknown.
Results
It has been revealed that expression levels of insulin gene transcription factors and incretin receptors are downregulated, which is closely associated with β-cell glucose toxicity. In addition, we have reported that it is more beneficial to use incretin-based drugs at an early stage of diabetes when incretin receptor expression in β-cells is preserved. Furthermore, we have reported that it is more beneficial for the prevention of atherosclerosis to use incretin-based drugs at an early stage when incretin receptor expression in arterial cells is preserved. On the other hand, although clinical trials with imeglimin in human subjects clearly indicated its efficacy and safety, its precise mechanism on β-cells remained unknown. However, to address this clinical question, we performed some basic experiments and confirmed the beneficial effects of imeglimin on mitochondrial morphology in β-cells and/or the number and quality of insulin granules, which can explain the effects of imeglimin on β-cells observed in clinical practice. In addition, we demonstrated that imeglimin exerted favorable effects on the development of atherosclerosis.
Conclusion
In this review article, we would like to show the importance of translational research bridging clinical practice and basic research, especially focusing on the molecular mechanism for pancreatic β-cell dysfunction and atherosclerosis and on the protective effects of imeglimin against β-cell dysfunction and atherosclerosis.
{"title":"Molecular mechanism for pancreatic β-cell dysfunction and atherosclerosis and its therapeutic application: Importance of translational research bridging clinical practice and basic research","authors":"Hideaki Kaneto, Tomohiko Kimura, Junpei Sanada, Yuichiro Iwamoto, Masashi Shimoda, Shuhei Nakanishi, Kohei Kaku","doi":"10.1111/jdi.70165","DOIUrl":"10.1111/jdi.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>It is well-known that when pancreatic β-cells are chronically exposed to hyperglycemia under diabetic conditions, β-cell function is gradually deteriorating. Although such phenomena were well-known as β-cell glucose toxicity in clinical practice, its molecular mechanism remained unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It has been revealed that expression levels of insulin gene transcription factors and incretin receptors are downregulated, which is closely associated with β-cell glucose toxicity. In addition, we have reported that it is more beneficial to use incretin-based drugs at an early stage of diabetes when incretin receptor expression in β-cells is preserved. Furthermore, we have reported that it is more beneficial for the prevention of atherosclerosis to use incretin-based drugs at an early stage when incretin receptor expression in arterial cells is preserved. On the other hand, although clinical trials with imeglimin in human subjects clearly indicated its efficacy and safety, its precise mechanism on β-cells remained unknown. However, to address this clinical question, we performed some basic experiments and confirmed the beneficial effects of imeglimin on mitochondrial morphology in β-cells and/or the number and quality of insulin granules, which can explain the effects of imeglimin on β-cells observed in clinical practice. In addition, we demonstrated that imeglimin exerted favorable effects on the development of atherosclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this review article, we would like to show the importance of translational research bridging clinical practice and basic research, especially focusing on the molecular mechanism for pancreatic β-cell dysfunction and atherosclerosis and on the protective effects of imeglimin against β-cell dysfunction and atherosclerosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2129-2136"},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204975","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}
The link between obesity and metabolic dysfunction is well-established. However, the choice of an anthropometric index best reflective of risk remains debatable. This study aimed to evaluate the predictive performance of several indices for diabetes and hypertension in a population at risk for cardiovascular disease.
Materials and methods
Data from 1,537 participants was analyzed. The predictive value of 19 indices for diabetes and hypertension was evaluated via area under the receiver operating characteristic curve (AUC) analysis. Analyses were adjusted for major risk factors to evaluate the independent utility of each index. Modified versions of the American Diabetes Association (ADA) diabetes risk assessment tool were examined, where body mass index (BMI) was substituted for indices demonstrating strong or independent predictive values.
Results
The Deurenberg formula was the best predictor of diabetes in both male (AUC = 0.67; 95% CI 0.62–0.73) and female (AUC = 0.77; 95% CI 0.73–0.82) participants, and significantly better than BMI. Body roundness index (BRI; aAUC = 0.63; 95% CI 0.56–0.70), waist-to-height ratio (WHtR; aAUC = 0.63; 95% CI 0.57–0.70), and waist-to-height1/2 ratio (WHT.5R; aAUC = 0.63; 95% CI 0.57–0.70) showed independent predictive values for diabetes in female participants. The risk assessment tool's performance was improved when BMI was substituted for these indices. BMI (aAUC = 0.66; 95% CI 0.61–0.70), Deurenberg (aAUC = 0.66; 95% CI 0.61–0.70), and Gallagher (aAUC = 0.66; 95% CI 0.62–0.70) formulas were independent predictors of hypertension in male participants.
Conclusions
Several indices showed promising performances for use in diabetes screening. Future research should focus on incorporating these indices in screening tools.
背景：肥胖和代谢功能障碍之间的联系是公认的。然而，选择一个最能反映风险的人体测量指数仍有争议。本研究旨在评估心血管疾病高危人群中糖尿病和高血压的几个指标的预测性能。材料和方法：对1537名参与者的数据进行分析。通过受试者工作特征曲线下面积（AUC）分析评价19项指标对糖尿病和高血压的预测价值。对主要危险因素进行分析调整，以评估每个指标的独立效用。对美国糖尿病协会（ADA）糖尿病风险评估工具的修改版本进行了检查，其中身体质量指数（BMI）取代了具有强或独立预测值的指数。结果：Deurenberg公式是男性（AUC = 0.67; 95% CI 0.62-0.73）和女性（AUC = 0.77; 95% CI 0.73-0.82）受试者中糖尿病的最佳预测因子，且显著优于BMI。体圆度指数（BRI; aAUC = 0.63; 95% CI 0.56-0.70）、腰高比（WHtR; aAUC = 0.63; 95% CI 0.57-0.70）和腰高1/2比（WHT.5R; aAUC = 0.63; 95% CI 0.57-0.70）显示了女性受试者糖尿病的独立预测值。用BMI代替这些指标后，风险评估工具的性能得到了提高。BMI公式（aAUC = 0.66; 95% CI 0.61-0.70）、Deurenberg公式（aAUC = 0.66; 95% CI 0.61-0.70）和Gallagher公式（aAUC = 0.66; 95% CI 0.62-0.70）是男性参与者高血压的独立预测因子。结论：几种指标在糖尿病筛查中具有良好的应用前景。未来的研究应侧重于将这些指标纳入筛选工具。
{"title":"Predictive performance of traditional and novel anthropometric indices for diabetes and hypertension","authors":"Mozhgan Pezeshki, Shirin Esmaeili, Armita Mahdavi-Gorabi, Tahereh Sadegi, Zahra Farhad Kiaee, Omid Assar, Kiavash Semnani, Mostafa Qorbani","doi":"10.1111/jdi.70172","DOIUrl":"10.1111/jdi.70172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The link between obesity and metabolic dysfunction is well-established. However, the choice of an anthropometric index best reflective of risk remains debatable. This study aimed to evaluate the predictive performance of several indices for diabetes and hypertension in a population at risk for cardiovascular disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Data from 1,537 participants was analyzed. The predictive value of 19 indices for diabetes and hypertension was evaluated via area under the receiver operating characteristic curve (AUC) analysis. Analyses were adjusted for major risk factors to evaluate the independent utility of each index. Modified versions of the American Diabetes Association (ADA) diabetes risk assessment tool were examined, where body mass index (BMI) was substituted for indices demonstrating strong or independent predictive values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Deurenberg formula was the best predictor of diabetes in both male (AUC = 0.67; 95% CI 0.62–0.73) and female (AUC = 0.77; 95% CI 0.73–0.82) participants, and significantly better than BMI. Body roundness index (BRI; aAUC = 0.63; 95% CI 0.56–0.70), waist-to-height ratio (WHtR; aAUC = 0.63; 95% CI 0.57–0.70), and waist-to-height<sup>1/2</sup> ratio (WHT.5R; aAUC = 0.63; 95% CI 0.57–0.70) showed independent predictive values for diabetes in female participants. The risk assessment tool's performance was improved when BMI was substituted for these indices. BMI (aAUC = 0.66; 95% CI 0.61–0.70), Deurenberg (aAUC = 0.66; 95% CI 0.61–0.70), and Gallagher (aAUC = 0.66; 95% CI 0.62–0.70) formulas were independent predictors of hypertension in male participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Several indices showed promising performances for use in diabetes screening. Future research should focus on incorporating these indices in screening tools.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2213-2224"},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211185","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>Hepatic insulin resistance is a key pathological feature of type 2 diabetes, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease (MASLD). It is characterized by a reduced responsiveness to insulin in hepatocytes and is closely associated with genetic susceptibility, chronic inflammation, and lipotoxicity/glucotoxicity<span><sup>1</sup></span>. However, the intrinsic molecular mechanisms remain poorly defined, largely due to the limited accessibility of human liver tissues. Circulating factors, including cytokines and metabolites, as well as adjoining stellate cells, endothelial cells, and circulating inflammatory cells, can regulate hepatic insulin signaling <i>in vivo</i>, which confounds the investigations of cell-intrinsic mechanisms. In a recent study published in <i>The Journal of Clinical Investigation</i>, Gattu <i>et al</i>.<span><sup>2</sup></span> developed a human induced pluripotent stem cell (iPSC)-derived hepatocyte model and utilized liquid chromatography with tandem mass spectrometry-based (LC–MS/MS-based) global phosphoproteomics to systematically reveal a novel cell-intrinsic signaling network of hepatic insulin resistance in type 2 diabetes (Figure 1).</p><p>Under physiological conditions, insulin signals through its receptor to recruit insulin receptor substrates (IRS) 1 and 2, thereby activating the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Activated AKT suppresses forkhead box protein O1 (FOXO1)-mediated gluconeogenesis, inhibits glycogen synthase kinase 3β (GSK3β) to enhance glycogen synthesis, and activates mechanistic target of rapamycin (mTOR) complex 1 to stimulate de novo lipogenesis (DNL), thereby maintaining hepatic and systemic metabolic homeostasis<span><sup>3</sup></span>. In insulin-resistant states, the liver displays a distinctive “selective insulin resistance”: the inhibitory effect of insulin on gluconeogenesis is impaired, while its lipogenic action is preserved or even amplified. Traditional perspectives ascribe this phenomenon to the weakening of classical PI3K/AKT signaling; however, this mechanism alone cannot fully explain the sustained activation of DNL. Current hypotheses propose several potential mechanisms: (1) differential subcellular localization and activity of IRS1 and IRS2; (2) distinct sensitivities of the hepatic glucose production and DNL pathways to AKT phosphorylation; and (3) the presence of an independent insulin signaling that specifically regulates DNL<span><sup>4</sup></span>. Due to the difficulty in obtaining primary human hepatocytes (PHHs), these hypotheses have not been validated at the level of intrinsic cellular signaling.</p><p>To investigate the intrinsic mechanisms of selective insulin resistance in human hepatocytes, Gattu <i>et al</i>.<span><sup>2</sup></span> enrolled 8 patients with type 2 diabetes and 8 age-matched healthy controls, and successfully generated human iPSC-derived hepatocytes (iHeps) from these individua
{"title":"Classical and emergent insulin signaling dual changes in type 2 diabetes revealed by human iPSC-derived hepatocytes","authors":"Shiyin Zheng, Xiaona Cui, Rui Wei, Tianpei Hong","doi":"10.1111/jdi.70171","DOIUrl":"10.1111/jdi.70171","url":null,"abstract":"<p>Hepatic insulin resistance is a key pathological feature of type 2 diabetes, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease (MASLD). It is characterized by a reduced responsiveness to insulin in hepatocytes and is closely associated with genetic susceptibility, chronic inflammation, and lipotoxicity/glucotoxicity<span><sup>1</sup></span>. However, the intrinsic molecular mechanisms remain poorly defined, largely due to the limited accessibility of human liver tissues. Circulating factors, including cytokines and metabolites, as well as adjoining stellate cells, endothelial cells, and circulating inflammatory cells, can regulate hepatic insulin signaling <i>in vivo</i>, which confounds the investigations of cell-intrinsic mechanisms. In a recent study published in <i>The Journal of Clinical Investigation</i>, Gattu <i>et al</i>.<span><sup>2</sup></span> developed a human induced pluripotent stem cell (iPSC)-derived hepatocyte model and utilized liquid chromatography with tandem mass spectrometry-based (LC–MS/MS-based) global phosphoproteomics to systematically reveal a novel cell-intrinsic signaling network of hepatic insulin resistance in type 2 diabetes (Figure 1).</p><p>Under physiological conditions, insulin signals through its receptor to recruit insulin receptor substrates (IRS) 1 and 2, thereby activating the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Activated AKT suppresses forkhead box protein O1 (FOXO1)-mediated gluconeogenesis, inhibits glycogen synthase kinase 3β (GSK3β) to enhance glycogen synthesis, and activates mechanistic target of rapamycin (mTOR) complex 1 to stimulate de novo lipogenesis (DNL), thereby maintaining hepatic and systemic metabolic homeostasis<span><sup>3</sup></span>. In insulin-resistant states, the liver displays a distinctive “selective insulin resistance”: the inhibitory effect of insulin on gluconeogenesis is impaired, while its lipogenic action is preserved or even amplified. Traditional perspectives ascribe this phenomenon to the weakening of classical PI3K/AKT signaling; however, this mechanism alone cannot fully explain the sustained activation of DNL. Current hypotheses propose several potential mechanisms: (1) differential subcellular localization and activity of IRS1 and IRS2; (2) distinct sensitivities of the hepatic glucose production and DNL pathways to AKT phosphorylation; and (3) the presence of an independent insulin signaling that specifically regulates DNL<span><sup>4</sup></span>. Due to the difficulty in obtaining primary human hepatocytes (PHHs), these hypotheses have not been validated at the level of intrinsic cellular signaling.</p><p>To investigate the intrinsic mechanisms of selective insulin resistance in human hepatocytes, Gattu <i>et al</i>.<span><sup>2</sup></span> enrolled 8 patients with type 2 diabetes and 8 age-matched healthy controls, and successfully generated human iPSC-derived hepatocytes (iHeps) from these individua","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2137-2139"},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204973","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 assess the longitudinal changes in cognitive function and associated factors in older patients with type 1 diabetes mellitus without dementia.
Materials and Methods
Older patients above 65 years of age with type 1 diabetes mellitus and without dementia were included in this study. They were assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment, Japanese version, at baseline and 3 years after. Cognitive decline was defined as a reduction of two or more points in the total Montreal Cognitive Assessment score over 3 years. Baseline diabetes-related factors were compared between the cognitive decrement and non-decrement groups to identify risk factors associated with cognitive impairment.
Results
Twenty-eight patients aged 71.5 ± 4.0 years were included. Total scores for the Mini-Mental State Examination and the Montreal Cognitive Assessment (Japanese version) at baseline and after 3 years of follow-up showed no significant changes (P = 0.38, P = 0.26). Delayed recall sub-scores of both tests were significantly lower after 3 years compared to their corresponding levels at baseline (P = 0.007, P = 0.04); 32% experienced impaired cognition after 3 years compared to baseline examination. Decline in total Montreal Cognitive Assessment score was significantly associated with the onset age (β = 0.54, P = 0.026) and duration of type-1 diabetes mellitus (β = −4.77, P = 0.026).
Conclusions
Patients with type-1 diabetes mellitus without dementia experience a progressive decline in memory over time. Long durations of type-1 diabetes mellitus are associated with cognitive decline even without dementia.
目的：本研究旨在评估老年1型糖尿病合并痴呆患者认知功能的纵向变化及其相关因素。材料与方法：本研究纳入年龄大于65岁的老年1型糖尿病患者，且无痴呆。在基线和3年后，使用简易精神状态检查和蒙特利尔认知评估（日语版）对他们进行评估。认知能力下降被定义为蒙特利尔认知能力评估总分在3年内下降2分或更多。比较认知功能减退组和非认知功能减退组的基线糖尿病相关因素，以确定与认知功能减退相关的危险因素。结果：纳入28例患者，年龄71.5±4.0岁。迷你精神状态检查和蒙特利尔认知评估（日语版）总分在基线和随访3年后无显著变化（P = 0.38, P = 0.26）。3年后，两项测试的延迟回忆分值均显著低于基线时的相应水平（P = 0.007, P = 0.04）；与基线检查相比，32%的人在3年后出现认知障碍。蒙特利尔认知评估总分下降与发病年龄（β = 0.54, P = 0.026）和1型糖尿病病程（β = -4.77, P = 0.026）显著相关。结论：无痴呆的1型糖尿病患者随着时间的推移记忆力逐渐下降。即使没有痴呆，长期的1型糖尿病也与认知能力下降有关。
{"title":"Longitudinal changes in cognitive function and its related factors in older type 1 diabetes mellitus patients without dementia","authors":"Kaoru Nagasawa, Kimio Matsumura, Takayasu Uchida, Yuya Suzuki, Akihiro Nishimura, Yukifusa Igeta, Takashi Sakurai, Yasumichi Mori","doi":"10.1111/jdi.70168","DOIUrl":"10.1111/jdi.70168","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to assess the longitudinal changes in cognitive function and associated factors in older patients with type 1 diabetes mellitus without dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Older patients above 65 years of age with type 1 diabetes mellitus and without dementia were included in this study. They were assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment, Japanese version, at baseline and 3 years after. Cognitive decline was defined as a reduction of two or more points in the total Montreal Cognitive Assessment score over 3 years. Baseline diabetes-related factors were compared between the cognitive decrement and non-decrement groups to identify risk factors associated with cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-eight patients aged 71.5 ± 4.0 years were included. Total scores for the Mini-Mental State Examination and the Montreal Cognitive Assessment (Japanese version) at baseline and after 3 years of follow-up showed no significant changes (<i>P</i> = 0.38, <i>P</i> = 0.26). Delayed recall sub-scores of both tests were significantly lower after 3 years compared to their corresponding levels at baseline (<i>P</i> = 0.007, <i>P</i> = 0.04); 32% experienced impaired cognition after 3 years compared to baseline examination. Decline in total Montreal Cognitive Assessment score was significantly associated with the onset age (<i>β</i> = 0.54, <i>P</i> = 0.026) and duration of type-1 diabetes mellitus (<i>β</i> = −4.77, <i>P</i> = 0.026).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with type-1 diabetes mellitus without dementia experience a progressive decline in memory over time. Long durations of type-1 diabetes mellitus are associated with cognitive decline even without dementia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2234-2241"},"PeriodicalIF":3.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190514","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}
In conclusion, this study makes a significant contribution by highlighting sex-specific disparities in depression among individuals with type 2 diabetes in South Asia. Addressing limitations such as study design, unmeasured psychosocial factors, and clinical comorbidities in future research will strengthen the validity and applicability of these findings.
The authors declare no conflicts of interest.
Approval of the research protocol: No ethics approval was required for this study.
Informed consent: N/A.
Approval date of Registry and the Registration No. of the study/trial: N/A.
Animal Studies: N/A.
The authors declare that no funds, grants, or other support was received during the preparation of this manuscript.
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
{"title":"Letter to the editor in response to “The relationship between depressive symptoms and glycemic control is stronger in women with type 2 diabetes in South Asians: Results from a cross-sectional multicenter study”","authors":"Sohrab Khan, Muhammad Zubair","doi":"10.1111/jdi.70170","DOIUrl":"10.1111/jdi.70170","url":null,"abstract":"<p>Dear Editor,</p><p>In conclusion, this study makes a significant contribution by highlighting sex-specific disparities in depression among individuals with type 2 diabetes in South Asia. Addressing limitations such as study design, unmeasured psychosocial factors, and clinical comorbidities in future research will strengthen the validity and applicability of these findings.</p><p>The authors declare no conflicts of interest.</p><p>Approval of the research protocol: No ethics approval was required for this study.</p><p>Informed consent: N/A.</p><p>Approval date of Registry and the Registration No. of the study/trial: N/A.</p><p>Animal Studies: N/A.</p><p>The authors declare that no funds, grants, or other support was received during the preparation of this manuscript.</p><p>Data sharing not applicable to this article as no datasets were generated or analysed during the current study.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190511","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}
Red blood cell distribution width (RDW) is a parameter of erythrocyte volume heterogeneity that has been traditionally used as an indicator of anemia and other hematopoietic abnormalities. Although the RDW-coefficient of variation (RDW-CV) increases in individuals with diabetes, its clinical significance in diabetic kidney disease (DKD), including glomerular and tubular injury, is unclear. Therefore, we aimed to clarify the relationship between RDW-CV and DKD indices in individuals with type 2 diabetes.
Materials and Methods
This was a multicenter, retrospective, cross-sectional study. In 490 Japanese individuals with type 2 diabetes (309 men and 181 women), multiple regression analysis was performed to examine the degree of association between DKD indices (estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (uACR), log-transformed uACR (Log-uACR), urinary liver-type fatty acid-binding protein (uL-FABP)-to-creatinine ratio (uL-FABPCR), and log-transformed uL-FABPCR (Log-uL-FABPCR)) and clinical confounding factors, including RDW-CV.
Results
No significant associations were identified between RDW-CV and eGFR, uACR, or Log-uACR in either the simple or multiple linear regression analyses. However, significant and independent positive associations between RDW-CV and both uL-FABPCR and Log-uL-FABPCR were identified in multiple regression analyses (P = 0.002 and P = 0.034, respectively). Additionally, logistic regression analysis showed that RDW-CV was an aggravating factor for the incidence of advanced tubular injury [odds ratio, 1.241 (95% confidence interval: 1.010–1.520), P = 0.037].
Conclusions
RDW-CV was independently and positively correlated with urinary excretion of L-FABP. Therefore, RDW-CV may be a simple and useful biomarker for detecting renal tubular injury in individuals with type 2 diabetes.
{"title":"Red blood cell distribution width is associated with renal tubular injury in individuals with type 2 diabetes","authors":"Kohsuke Miyataka, Yousuke Kaneko, Taiki Hori, Yuki Yamaguchi, Seijiro Tsuji, Tomoyo Hara, Hiroki Yamagami, Sumiko Yoshida, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Takeshi Harada, Hirokazu Miki, Shingen Nakamura, Itsuro Endo, Munehide Matsuhisa, Ken-ichi Matsuoka, Ken-ichi Aihara","doi":"10.1111/jdi.70149","DOIUrl":"10.1111/jdi.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Red blood cell distribution width (RDW) is a parameter of erythrocyte volume heterogeneity that has been traditionally used as an indicator of anemia and other hematopoietic abnormalities. Although the RDW-coefficient of variation (RDW-CV) increases in individuals with diabetes, its clinical significance in diabetic kidney disease (DKD), including glomerular and tubular injury, is unclear. Therefore, we aimed to clarify the relationship between RDW-CV and DKD indices in individuals with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This was a multicenter, retrospective, cross-sectional study. In 490 Japanese individuals with type 2 diabetes (309 men and 181 women), multiple regression analysis was performed to examine the degree of association between DKD indices (estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (uACR), log-transformed uACR (Log-uACR), urinary liver-type fatty acid-binding protein (uL-FABP)-to-creatinine ratio (uL-FABPCR), and log-transformed uL-FABPCR (Log-uL-FABPCR)) and clinical confounding factors, including RDW-CV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant associations were identified between RDW-CV and eGFR, uACR, or Log-uACR in either the simple or multiple linear regression analyses. However, significant and independent positive associations between RDW-CV and both uL-FABPCR and Log-uL-FABPCR were identified in multiple regression analyses (<i>P</i> = 0.002 and <i>P</i> = 0.034, respectively). Additionally, logistic regression analysis showed that RDW-CV was an aggravating factor for the incidence of advanced tubular injury [odds ratio, 1.241 (95% confidence interval: 1.010–1.520), <i>P</i> = 0.037].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>RDW-CV was independently and positively correlated with urinary excretion of L-FABP. Therefore, RDW-CV may be a simple and useful biomarker for detecting renal tubular injury in individuals with type 2 diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2191-2200"},"PeriodicalIF":3.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190557","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 non-invasive fingertip autofluorescence can evaluate micro- and macrovascular complications in patients with type 2 diabetes.
Materials and Methods
This multicenter cross-sectional study recruited 452 patients with type 2 diabetes between August 2017 and January 2023. Fingertip autofluorescence levels were measured using AGEs Sensor (Air Water Biodesign, Kobe, Japan).
Results
Fingertip autofluorescence correlated with body mass index, glycated hemoglobin, estimated glomerular filtration rate, and duration of diabetes. Fingertip autofluorescence was increased in parallel with the number of micro- and macrovascular complications. A significant relationship was noted between fingertip autofluorescence as a dependent variable and sex, serum albumin, history of diabetic nephropathy, and coronary arterial disease as independent variables. Logistic regression analysis indicated the association of fingertip autofluorescence as a dichotomous variable with diabetic nephropathy as a significant predictor variable adjusted for age, sex, duration of diabetes, smoking status, and serum albumin. The receiver operating characteristic curve revealed that fingertip autofluorescence could be used to identify the presence of macrovascular complications (area under the curve: 0.65, 95% confidence interval: 0.585–0.707, P < 0.001).
Conclusions
Fingertip autofluorescence may be a convenient and non-invasive potential marker for evaluating micro- and macrovascular complications in patients with type 2 diabetes.
目的/简介：本研究旨在探讨无创指尖自体荧光是否可以评估2型糖尿病患者的微血管和大血管并发症。材料和方法：这项多中心横断面研究在2017年8月至2023年1月期间招募了452例2型糖尿病患者。使用AGEs传感器（Air Water Biodesign, Kobe, Japan）测量指尖自身荧光水平。结果：指尖自身荧光与体重指数、糖化血红蛋白、肾小球滤过率和糖尿病病程相关。指尖自身荧光随微血管和大血管并发症数量的增加而增加。指尖自身荧光作为因变量与性别、血清白蛋白、糖尿病肾病史和冠状动脉疾病作为自变量之间存在显著关系。Logistic回归分析表明，指尖自身荧光作为二分类变量与糖尿病肾病相关，作为一个显著的预测变量，调整了年龄、性别、糖尿病病程、吸烟状况和血清白蛋白。受者工作特征曲线显示，指尖自身荧光可用于识别大血管并发症的存在（曲线下面积：0.65,95%可信区间：0.585-0.707，P）。结论：指尖自身荧光可作为评估2型糖尿病患者微血管和大血管并发症的一种便捷、无创的潜在标志物。
{"title":"Fingertip skin autofluorescence as a non-invasive marker for vascular complications in patients with type 2 diabetes","authors":"Minoru Takeshita, Takeshi Matsumura, Aiko Arimura, Hiroyuki Takahashi, Yoshimi Muta, Shigeru Kawade, Dai Yamagami, Takahisa Deguchi, Tatsuya Kondo, Mikihiro Yamanaka, Ryoji Nagai, Daiji Kawanami, Toshihiko Yanase, Takashi Nomiyama, Yoshihiko Nishio, Eiichi Araki, Naoto Kubota","doi":"10.1111/jdi.70169","DOIUrl":"10.1111/jdi.70169","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>This study aimed to investigate whether non-invasive fingertip autofluorescence can evaluate micro- and macrovascular complications in patients with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This multicenter cross-sectional study recruited 452 patients with type 2 diabetes between August 2017 and January 2023. Fingertip autofluorescence levels were measured using AGEs Sensor (Air Water Biodesign, Kobe, Japan).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fingertip autofluorescence correlated with body mass index, glycated hemoglobin, estimated glomerular filtration rate, and duration of diabetes. Fingertip autofluorescence was increased in parallel with the number of micro- and macrovascular complications. A significant relationship was noted between fingertip autofluorescence as a dependent variable and sex, serum albumin, history of diabetic nephropathy, and coronary arterial disease as independent variables. Logistic regression analysis indicated the association of fingertip autofluorescence as a dichotomous variable with diabetic nephropathy as a significant predictor variable adjusted for age, sex, duration of diabetes, smoking status, and serum albumin. The receiver operating characteristic curve revealed that fingertip autofluorescence could be used to identify the presence of macrovascular complications (area under the curve: 0.65, 95% confidence interval: 0.585–0.707, <i>P</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Fingertip autofluorescence may be a convenient and non-invasive potential marker for evaluating micro- and macrovascular complications in patients with type 2 diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2201-2212"},"PeriodicalIF":3.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184348","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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