Pub Date : 2025-10-25DOI: 10.1007/s00592-025-02591-3
Angelo Di Vincenzo, Marika Crescenzi, Marnie Granzotto, Federico Capone, Fausto Cortese, Paola Fioretto, Roberto Vettor, Marco Rossato
{"title":"Could the heparanase/TGF-β axis modulation be considered for the SGLT2 inhibitors cardioprotection in obesity? A hypothesis-generating report","authors":"Angelo Di Vincenzo, Marika Crescenzi, Marnie Granzotto, Federico Capone, Fausto Cortese, Paola Fioretto, Roberto Vettor, Marco Rossato","doi":"10.1007/s00592-025-02591-3","DOIUrl":"10.1007/s00592-025-02591-3","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 1","pages":"171 - 174"},"PeriodicalIF":2.9,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic gastroparesis is characterized by delayed gastric emptying due to diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes who have poor glycemic control, significantly impairing their quality of life. IGF-1 presents significant potential as a therapeutic target for DGP due to its neuroprotective effects and its role in inhibiting smooth muscle cell apoptosis. By promoting the survival and regeneration of interstitial cells of Cajal and reducing inflammation, IGF-1 could enhance gastrointestinal regulation, thereby improving gastric motility and alleviating DGP symptoms. Although IGF-1 has not yet been utilized as a targeted therapy for DGP, its ability to modulate key signaling pathways, such as SCF/C-Kit, PI3K/AKT, and ERK/MAPK, suggests promising therapeutic avenues. Future research should focus on investigating these mechanisms to determine IGF-1’s precise role in DGP pathophysiology and explore its clinical applications.
{"title":"Investigating the role of IGF-1 in diabetic gastroparesis: a preliminary review","authors":"Yifan Lu, Wei Wei, Hao Chen, Yixuan Xie, Jie Tian, Ziming Zhao, Qibiao Wu, Xiqiao Zhou","doi":"10.1007/s00592-025-02578-0","DOIUrl":"10.1007/s00592-025-02578-0","url":null,"abstract":"<div><p>Diabetic gastroparesis is characterized by delayed gastric emptying due to diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes who have poor glycemic control, significantly impairing their quality of life. IGF-1 presents significant potential as a therapeutic target for DGP due to its neuroprotective effects and its role in inhibiting smooth muscle cell apoptosis. By promoting the survival and regeneration of interstitial cells of Cajal and reducing inflammation, IGF-1 could enhance gastrointestinal regulation, thereby improving gastric motility and alleviating DGP symptoms. Although IGF-1 has not yet been utilized as a targeted therapy for DGP, its ability to modulate key signaling pathways, such as SCF/C-Kit, PI3K/AKT, and ERK/MAPK, suggests promising therapeutic avenues. Future research should focus on investigating these mechanisms to determine IGF-1’s precise role in DGP pathophysiology and explore its clinical applications.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 1","pages":"163 - 170"},"PeriodicalIF":2.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder that creates considerable risks regarding both maternal and fetal health. Conventional screening approaches for GDM which are typically performed in the late second trimester; frequently miss an important window for early intervention.
Methods: This meta-analysis seeks to evaluate the diagnostic accuracy of first-trimester maternal serum biomarkers, particularly pregnancy-associated plasma protein-A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG), in the prediction of GDM. This systematic review of observational studies was conducted to assess PAPP-A and/or β-hCG levels during the first trimester, examining their correlation with the subsequent diagnosis of GDM. This meta-analysis collected data from numerous studies to evaluate sensitivity, specificity, likelihood ratios and diagnostic odds ratios; alongside with developing summary receiver operating characteristic (sROC) curves.
Results: This diagnostic meta-analysis assessed 23 studies encompassing first-trimester PAPP-A and β-hCG measurements with regards to early prediction of GDM. The overall pooled sensitivity and specificity were found to be 63% (95% CI: 53-73%) and 70% (95% CI: 61-78%), alongside an AUC of 0.72 (95% CI: 0.68-0.76). Substantial heterogeneity was observed regarding both sensitivity and specificity (I² >95%). Unaccompanied PAPP-A showed a sensitivity of 67% (95% CI: 55-77%) and specificity of 66% (95% CI: 54-76%) with AUC of 0.71, while β-hCG alone exhibited low sensitivity of 29% (95% CI: 7-69%) despite a high specificity of 87% (95% CI: 64-96%) with its AUC found to be 0.71. Fagan's analysis revealed modest clinical impact; which was found to be raising post-test probability from 20% to ~ 39% after a positive result. Deek's tests suggested no major publication bias (p = 0.45 for overall, 0.41 for PAPP-A, 0.08 for β-hCG). Subgroup analyses revealed higher sensitivity levels in studies utilizing ADA criteria and in studies with smaller samples, while those with cohort designs generated more conservative estimates upon comparison with their case-control counterparts.
Conclusion: First-trimester PAPP-A and β-hCG are found to express modest diagnostic accuracy and therefore are best considered as adjuncts to early risk stratification regarding GDM. PAPP-A, as stand-alone, provides balanced though moderate levels of sensitivity and specificity, whereas β-hCG shows high specificity levels but very low sensitivity level; thus, limiting its independent predictive value. Neither biomarker is found to be sufficient as a stand-alone diagnostic tool, but both may contribute to comprehensive risk models which might inform timely intervention. Future research should emphasize standardized methodologies and validation in large, diverse populations in order to improve clinical applicability.
{"title":"Diagnostic performance of PAPP-A and β-hCG in early detection of gestational diabetes mellitus: a meta-analysis.","authors":"Maryam Rahimi, Ladan Haghighi, Mostafa Majidnia, Babak Ghadirzadeh, Yousef Moradi","doi":"10.1007/s00592-025-02597-x","DOIUrl":"https://doi.org/10.1007/s00592-025-02597-x","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) is a common metabolic disorder that creates considerable risks regarding both maternal and fetal health. Conventional screening approaches for GDM which are typically performed in the late second trimester; frequently miss an important window for early intervention.</p><p><strong>Methods: </strong>This meta-analysis seeks to evaluate the diagnostic accuracy of first-trimester maternal serum biomarkers, particularly pregnancy-associated plasma protein-A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG), in the prediction of GDM. This systematic review of observational studies was conducted to assess PAPP-A and/or β-hCG levels during the first trimester, examining their correlation with the subsequent diagnosis of GDM. This meta-analysis collected data from numerous studies to evaluate sensitivity, specificity, likelihood ratios and diagnostic odds ratios; alongside with developing summary receiver operating characteristic (sROC) curves.</p><p><strong>Results: </strong>This diagnostic meta-analysis assessed 23 studies encompassing first-trimester PAPP-A and β-hCG measurements with regards to early prediction of GDM. The overall pooled sensitivity and specificity were found to be 63% (95% CI: 53-73%) and 70% (95% CI: 61-78%), alongside an AUC of 0.72 (95% CI: 0.68-0.76). Substantial heterogeneity was observed regarding both sensitivity and specificity (I² >95%). Unaccompanied PAPP-A showed a sensitivity of 67% (95% CI: 55-77%) and specificity of 66% (95% CI: 54-76%) with AUC of 0.71, while β-hCG alone exhibited low sensitivity of 29% (95% CI: 7-69%) despite a high specificity of 87% (95% CI: 64-96%) with its AUC found to be 0.71. Fagan's analysis revealed modest clinical impact; which was found to be raising post-test probability from 20% to ~ 39% after a positive result. Deek's tests suggested no major publication bias (p = 0.45 for overall, 0.41 for PAPP-A, 0.08 for β-hCG). Subgroup analyses revealed higher sensitivity levels in studies utilizing ADA criteria and in studies with smaller samples, while those with cohort designs generated more conservative estimates upon comparison with their case-control counterparts.</p><p><strong>Conclusion: </strong>First-trimester PAPP-A and β-hCG are found to express modest diagnostic accuracy and therefore are best considered as adjuncts to early risk stratification regarding GDM. PAPP-A, as stand-alone, provides balanced though moderate levels of sensitivity and specificity, whereas β-hCG shows high specificity levels but very low sensitivity level; thus, limiting its independent predictive value. Neither biomarker is found to be sufficient as a stand-alone diagnostic tool, but both may contribute to comprehensive risk models which might inform timely intervention. Future research should emphasize standardized methodologies and validation in large, diverse populations in order to improve clinical applicability.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-15DOI: 10.1007/s00592-025-02596-y
Xiaoyan Wang, Run Yang, Jingxiang Li, Yongqi Liang, Chenxi Jin, Yining Xu, Xianbo Wu, Mengchen Zou
Background: Excess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect systemic inflammation. Currently, there is a lack of effective clinical tools for early risk stratification and intervention in physically active people.
Methods: This was a prospective cohort of 72,262 overweight but physically active persons in the UK Biobank. The TyG was combined with hsCRP, waist circumference (WC), or body mass index (BMI) as indices of IR. Adjusted Cox regression, interaction tests, restricted cubic splines (RCS) analysis, Kaplan-Meier analysis, and Harrell's C-index were used to examine the relations and time-dependent predictive power.
Results: During 12.7 years of follow-up, 1,477 participants developed metabolic dysfunction-associated fatty liver disease (MAFLD). RCS analysis suggested TyG-hsCRP had a nonlinear positive correlations with all-cause mortality. Compared to the lowest quartile group, the corrected hazard ratio (HR) (95% confidence interval [CI]) of new-onset MAFLD in maximum quartile groups for TyG-hsCRP was 1.94(1.62-2.32), for TyG-WC was 1.78(1.44-2.18), for TyG-BMI was 1.36(1.12-1.65), and for TyG was 1.41(1.15-1.72). The relation between C-index of TyG-hsCRP and MAFLD was higher than that of other TyG indices. Similar results were observed in all-cause mortality.
Conclusion: TyG-hsCRP is superior to other indices for identifying risk of MAFLD and all-cause mortality in overweight but physically active people. Our findings suggest the importance of inflammatory metabolism and provide evidence for effectively early anti-inflammatory treatments.
{"title":"The close relationship between inflammation and insulin resistance: a comparative perspective from a new angle.","authors":"Xiaoyan Wang, Run Yang, Jingxiang Li, Yongqi Liang, Chenxi Jin, Yining Xu, Xianbo Wu, Mengchen Zou","doi":"10.1007/s00592-025-02596-y","DOIUrl":"https://doi.org/10.1007/s00592-025-02596-y","url":null,"abstract":"<p><strong>Background: </strong>Excess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect systemic inflammation. Currently, there is a lack of effective clinical tools for early risk stratification and intervention in physically active people.</p><p><strong>Methods: </strong>This was a prospective cohort of 72,262 overweight but physically active persons in the UK Biobank. The TyG was combined with hsCRP, waist circumference (WC), or body mass index (BMI) as indices of IR. Adjusted Cox regression, interaction tests, restricted cubic splines (RCS) analysis, Kaplan-Meier analysis, and Harrell's C-index were used to examine the relations and time-dependent predictive power.</p><p><strong>Results: </strong>During 12.7 years of follow-up, 1,477 participants developed metabolic dysfunction-associated fatty liver disease (MAFLD). RCS analysis suggested TyG-hsCRP had a nonlinear positive correlations with all-cause mortality. Compared to the lowest quartile group, the corrected hazard ratio (HR) (95% confidence interval [CI]) of new-onset MAFLD in maximum quartile groups for TyG-hsCRP was 1.94(1.62-2.32), for TyG-WC was 1.78(1.44-2.18), for TyG-BMI was 1.36(1.12-1.65), and for TyG was 1.41(1.15-1.72). The relation between C-index of TyG-hsCRP and MAFLD was higher than that of other TyG indices. Similar results were observed in all-cause mortality.</p><p><strong>Conclusion: </strong>TyG-hsCRP is superior to other indices for identifying risk of MAFLD and all-cause mortality in overweight but physically active people. Our findings suggest the importance of inflammatory metabolism and provide evidence for effectively early anti-inflammatory treatments.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-15DOI: 10.1007/s00592-025-02594-0
Fei Huang, Yan Zhou, Hairong Wu, Feifei Ma
Background: Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenesis, which is essential for the treatment of Diabetic foot ulcers (DFU).
Methods: Direct targeting of miR-125a-5p to Glutathione S-Transferase M5 (GSTM5) was demonstrated by dual luciferase assays. MiR-125a-5p and GSTM5 were induced or silenced by HGM in endothelial cells in vitro, and the results were compared with a blank control to determine the mechanism of miR-125a-5p and GSTM5 expression levels on DFU.
Results: Initial analysis revealed distinct expression patterns of miR-125a-5p and GSTM5 between acute and chronic DFU patients. Their regulatory roles were investigated by comparing differential expression profiles in these two patient groups. We found that low expression of both in chronic DFU patients was positively correlated with changes in angiogenic markers. Inhibition of miR-125a-5p and GSTM5 in endothelial cells in vitro yielded the same results, demonstrating the promote angiogenesis of their expression on angiogenesis.
Conclusion: MiR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.
{"title":"miR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.","authors":"Fei Huang, Yan Zhou, Hairong Wu, Feifei Ma","doi":"10.1007/s00592-025-02594-0","DOIUrl":"https://doi.org/10.1007/s00592-025-02594-0","url":null,"abstract":"<p><strong>Background: </strong>Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenesis, which is essential for the treatment of Diabetic foot ulcers (DFU).</p><p><strong>Methods: </strong>Direct targeting of miR-125a-5p to Glutathione S-Transferase M5 (GSTM5) was demonstrated by dual luciferase assays. MiR-125a-5p and GSTM5 were induced or silenced by HGM in endothelial cells in vitro, and the results were compared with a blank control to determine the mechanism of miR-125a-5p and GSTM5 expression levels on DFU.</p><p><strong>Results: </strong>Initial analysis revealed distinct expression patterns of miR-125a-5p and GSTM5 between acute and chronic DFU patients. Their regulatory roles were investigated by comparing differential expression profiles in these two patient groups. We found that low expression of both in chronic DFU patients was positively correlated with changes in angiogenic markers. Inhibition of miR-125a-5p and GSTM5 in endothelial cells in vitro yielded the same results, demonstrating the promote angiogenesis of their expression on angiogenesis.</p><p><strong>Conclusion: </strong>MiR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13DOI: 10.1007/s00592-025-02586-0
Luisa M Saldarriaga-Callejas, Piyush Ratan, Eric Pasqualotto, Ticiane Bovi, Talita Trevisan
Introduction and objective: Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. This meta-analysis aims to provide an updated evaluation of the impact of a carbohydrate-last (CL) strategy, compared to carbohydrate-first or unordered (CF) intake, on metabolic parameters in adults with T2D.
Methods: A systematic search was conducted in PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was assessed using Cochrane's Q test and I² statistics. Analyses were conducted using R, version 4.4.2.
Results: Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 60 min (MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p < 0.01) and 120 min (MD: -13.00 mg/dL; 95% CI: -21.07, -4.94; p < 0.01), higher postprandial glucagon-like peptide-1 (GLP-1) levels (MD: 8.21 pmol/L; 95% CI: 2.34, 14.09; p < 0.01), delayed gastric emptying half-time (MD: 28.14 min; 95% CI: 16.06, 40.23; p < 0.01), and reduced glycated hemoglobin (HbA1c) at follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p = 0.04).
Conclusion: Carbohydrate-last eating pattern has been shown to improve postprandial glycemia, enhance GLP-1 secretion, and delay gastric emptying, with a minimal effect on HbA1c in individuals with mild T2D. Further research is needed to confirm its applicability in advanced disease stages and to establish long-term metabolic benefits.
{"title":"Nutrient intake order on metabolic outcomes in type 2 diabetes: a systematic review and meta-analysis.","authors":"Luisa M Saldarriaga-Callejas, Piyush Ratan, Eric Pasqualotto, Ticiane Bovi, Talita Trevisan","doi":"10.1007/s00592-025-02586-0","DOIUrl":"https://doi.org/10.1007/s00592-025-02586-0","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. This meta-analysis aims to provide an updated evaluation of the impact of a carbohydrate-last (CL) strategy, compared to carbohydrate-first or unordered (CF) intake, on metabolic parameters in adults with T2D.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was assessed using Cochrane's Q test and I² statistics. Analyses were conducted using R, version 4.4.2.</p><p><strong>Results: </strong>Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 60 min (MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p < 0.01) and 120 min (MD: -13.00 mg/dL; 95% CI: -21.07, -4.94; p < 0.01), higher postprandial glucagon-like peptide-1 (GLP-1) levels (MD: 8.21 pmol/L; 95% CI: 2.34, 14.09; p < 0.01), delayed gastric emptying half-time (MD: 28.14 min; 95% CI: 16.06, 40.23; p < 0.01), and reduced glycated hemoglobin (HbA1c) at follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p = 0.04).</p><p><strong>Conclusion: </strong>Carbohydrate-last eating pattern has been shown to improve postprandial glycemia, enhance GLP-1 secretion, and delay gastric emptying, with a minimal effect on HbA1c in individuals with mild T2D. Further research is needed to confirm its applicability in advanced disease stages and to establish long-term metabolic benefits.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-07DOI: 10.1007/s00592-025-02582-4
Subhasri Bogadi, Md Ekhtiar Uddin, Veera Venkata Satyanarayana Reddy Karri, Rahima Begum, Mohammed Abdul Kader, Shahabe S. Abullais, Md Shahin Reza, Athanasios Alexiou, Marios Papadakis
Diabetes is the most serious consequence of Type 2 Diabetes Mellitus, which affects almost all vital organs in the human body. According to the World Health Organization, 537 million adults worldwide are affected by diabetes and its complications. By 2030, this figure is expected to reach 643 million, and by 2045, it will reach 783 million. Up to 25% of diabetic patients experience the equivalent foot Ulcer (Diabetic wound). Infections result in hospitalization in more than 50% of wounds, and 20% of infections necessitate amputations. In India, people with DWs account for 80% of all non-traumatic amputations performed yearly. The rise in blood sugar levels, reflected by a chronic hyperglycemic state, is a significant contributor to the failure of the healing process. This is because the extremities do not get enough blood, which reduces oxygen. In diabetic wounds, oxidative stress plays a critical role in stabilizing Hypoxia hypoxia-inducible factor (HIF-1 α). Numerous researchers have looked into the theory that oxidative stress in a specific area causes delayed chronic diabetic wounds. Some of the existing remedies, such as hyperbaric oxygen inhalation therapy (HBO) and other topical gaseous oxygen (TGO) administration, have certain drawbacks, such as the inability to stop oxidative stress in particular regions of the wound that cannot synthesize oxygen in the target site. Therefore, it is crucial to reduce oxidative stress in chronic diabetic wounds. In this review, we focus on metal oxide-related nanoparticles such as copper II oxide, which act as an anti-oxidant activity property by lowering the oxidative stress and stabilizing Hypoxia Inducible Factor (HIF), which in turn encourages proangiogenic factors and vascular endothelial growth factors to aid in wound healing.
{"title":"Therapeutic potential of copper II oxide in treating diabetic wounds: an emerging approach for enhanced healing","authors":"Subhasri Bogadi, Md Ekhtiar Uddin, Veera Venkata Satyanarayana Reddy Karri, Rahima Begum, Mohammed Abdul Kader, Shahabe S. Abullais, Md Shahin Reza, Athanasios Alexiou, Marios Papadakis","doi":"10.1007/s00592-025-02582-4","DOIUrl":"10.1007/s00592-025-02582-4","url":null,"abstract":"<div><p>Diabetes is the most serious consequence of Type 2 Diabetes Mellitus, which affects almost all vital organs in the human body. According to the World Health Organization, 537 million adults worldwide are affected by diabetes and its complications. By 2030, this figure is expected to reach 643 million, and by 2045, it will reach 783 million. Up to 25% of diabetic patients experience the equivalent foot Ulcer (Diabetic wound). Infections result in hospitalization in more than 50% of wounds, and 20% of infections necessitate amputations. In India, people with DWs account for 80% of all non-traumatic amputations performed yearly. The rise in blood sugar levels, reflected by a chronic hyperglycemic state, is a significant contributor to the failure of the healing process. This is because the extremities do not get enough blood, which reduces oxygen. In diabetic wounds, oxidative stress plays a critical role in stabilizing Hypoxia hypoxia-inducible factor (HIF-1 α). Numerous researchers have looked into the theory that oxidative stress in a specific area causes delayed chronic diabetic wounds. Some of the existing remedies, such as hyperbaric oxygen inhalation therapy (HBO) and other topical gaseous oxygen (TGO) administration, have certain drawbacks, such as the inability to stop oxidative stress in particular regions of the wound that cannot synthesize oxygen in the target site. Therefore, it is crucial to reduce oxidative stress in chronic diabetic wounds. In this review, we focus on metal oxide-related nanoparticles such as copper II oxide, which act as an anti-oxidant activity property by lowering the oxidative stress and stabilizing Hypoxia Inducible Factor (HIF), which in turn encourages proangiogenic factors and vascular endothelial growth factors to aid in wound healing.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 1","pages":"145 - 157"},"PeriodicalIF":2.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-07DOI: 10.1007/s00592-025-02587-z
Xinglei Xie, Jiaming Liu, Alicia López, Apolonia García-Patterson, J. M. Adelantado, Esther López, Rosa Corcoy
Aims
To investigate the association between gestational weight gain (GWG) as per Institute of Medicine 2009 (IOM) and pregnancy outcomes in women with gestational (GDM) or preexisting diabetes mellitus (PDM), when applying or not a correction for gestational age (IOM-CGWG and IOM-GWG respectively).
Methods
We conducted a retrospective analysis of pregnant women with either GDM or PDM attended in our center. Exposure variables: IOM-GWG and IOM-CGWG. Outcome variables: Maternal and fetal/neonatal clinical outcomes. Statistics: Logistic regression with adjustment for other potential independent variables.
Results
In women with GDM, correction for gestational age did not affect the distribution of weight gain or the association with clinical outcomes (pregnancy-induced hypertension, preeclampsia, cesarean delivery, large-for-gestational age newborns (LGA), macrosomia and small-for-gestational age newborns (SGA)). In women with PDM, correction for gestational age, caused a shift in the distribution to a higher rate of excessive weight gain. In the adjusted analysis, IOM-GWG was significantly associated with cesarean delivery, preterm birth, LGA, macrosomia, SGA and neonatal respiratory distress. With IOM-CGWG, the association with preterm birth disappeared while an association with PIH emerged. Population-attributable and preventive fraction were substantial for both women with GDM and PDM.
Conclusions
We conclude that the associations of IOM-GWG and IOM-CGWG are substantial in both women with GDM and PDM, indicating an area for potential intervention. In women with PDM, the modification of associations when gestational age is accounted for is relevant, highlighting the importance of considering this variable.
{"title":"In women with pre-existing diabetes, the contribution to pregnancy outcomes of gestational weight gain as defined by IOM guidelines, differs when adjustment for gestational age is used","authors":"Xinglei Xie, Jiaming Liu, Alicia López, Apolonia García-Patterson, J. M. Adelantado, Esther López, Rosa Corcoy","doi":"10.1007/s00592-025-02587-z","DOIUrl":"10.1007/s00592-025-02587-z","url":null,"abstract":"<div><h3>Aims</h3><p>To investigate the association between gestational weight gain (GWG) as per Institute of Medicine 2009 (IOM) and pregnancy outcomes in women with gestational (GDM) or preexisting diabetes mellitus (PDM), when applying or not a correction for gestational age (IOM-CGWG and IOM-GWG respectively).</p><h3>Methods</h3><p>We conducted a retrospective analysis of pregnant women with either GDM or PDM attended in our center. Exposure variables: IOM-GWG and IOM-CGWG. Outcome variables: Maternal and fetal/neonatal clinical outcomes. Statistics: Logistic regression with adjustment for other potential independent variables.</p><h3>Results</h3><p>In women with GDM, correction for gestational age did not affect the distribution of weight gain or the association with clinical outcomes (pregnancy-induced hypertension, preeclampsia, cesarean delivery, large-for-gestational age newborns (LGA), macrosomia and small-for-gestational age newborns (SGA)). In women with PDM, correction for gestational age, caused a shift in the distribution to a higher rate of excessive weight gain. In the adjusted analysis, IOM-GWG was significantly associated with cesarean delivery, preterm birth, LGA, macrosomia, SGA and neonatal respiratory distress. With IOM-CGWG, the association with preterm birth disappeared while an association with PIH emerged. Population-attributable and preventive fraction were substantial for both women with GDM and PDM.</p><h3>Conclusions</h3><p>We conclude that the associations of IOM-GWG and IOM-CGWG are substantial in both women with GDM and PDM, indicating an area for potential intervention. In women with PDM, the modification of associations when gestational age is accounted for is relevant, highlighting the importance of considering this variable.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 1","pages":"159 - 162"},"PeriodicalIF":2.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-07DOI: 10.1007/s00592-025-02585-1
Roseleena Minz, Praveen Kumar Sharma
Background/aim: Emerging evidence links hyperglycemia, a "hallmark of diabetes mellitus" not only to peripheral metabolic dysfunction but also to its detrimental impact on brain health, often contributing to stress-related pathologies such as depression and cognitive decline. Zebrafish, with their well-characterized vascular system and behavioral assays, offer a unique model to study the impacts of sucrose-induced hyperglycemia. This study aims to investigates the effects of sucrose-induced hyperglycemia on stress mechanisms in type 2 diabetes using the zebrafish.
Methods: Male zebrafish were divided into two groups: control, and 55.5mM sucrose immersed. Over two weeks, these were subjected to behavioural assays- the novel tank test (NTT) and the light/dark test (LDT). The NTT assessed anxiety-related behaviour by measuring the time spent in different vertical zones of a novel tank, while the light/dark test evaluated anxiety responses based on the time spent in illuminated versus dark compartments. Trajectory body coordinates and tail kinematics were quantified using ZebraZoom software to asses locomotor metrics status. Cortisol levels were measured to assess HPA axis function. Antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), were quantified to evaluate oxidative stress.
Results: The results revealed that zebrafish exposed to sucrose exhibited significant hyperglycemia (**p < 0.01) and behavioural changes compared to those on control. Specifically, in the NTT, the hyperglycemic group demonstrated heightened anxiety-like behaviour, spending more time at the bottom zone of the tank. In the light/dark test, male zebrafish showed increased anxiety by spending more time in the dark compartment. Hyperglycemic zebrafish showed a significant blunting of the cortisol response, indicating impaired stress regulation. Additionally, SOD activity was increased, while CAT activity was decreased, suggesting an imbalance in antioxidative defense mechanisms.
Conclusion: The zebrafish system effectively models the negative impacts of sucrose-induced hyperglycemia, providing valuable insights into the stress mechanisms associated with type 2 diabetes. These findings demonstrate that hyperglycemia alters both endocrine stress response and antioxidant systems, potentially serving as biomarkers of systemic stress.
{"title":"Blunted cortisol and altered antioxidant defense as biomarkers of systemic stress in hyperglycemic Zebrafish.","authors":"Roseleena Minz, Praveen Kumar Sharma","doi":"10.1007/s00592-025-02585-1","DOIUrl":"https://doi.org/10.1007/s00592-025-02585-1","url":null,"abstract":"<p><strong>Background/aim: </strong>Emerging evidence links hyperglycemia, a \"hallmark of diabetes mellitus\" not only to peripheral metabolic dysfunction but also to its detrimental impact on brain health, often contributing to stress-related pathologies such as depression and cognitive decline. Zebrafish, with their well-characterized vascular system and behavioral assays, offer a unique model to study the impacts of sucrose-induced hyperglycemia. This study aims to investigates the effects of sucrose-induced hyperglycemia on stress mechanisms in type 2 diabetes using the zebrafish.</p><p><strong>Methods: </strong>Male zebrafish were divided into two groups: control, and 55.5mM sucrose immersed. Over two weeks, these were subjected to behavioural assays- the novel tank test (NTT) and the light/dark test (LDT). The NTT assessed anxiety-related behaviour by measuring the time spent in different vertical zones of a novel tank, while the light/dark test evaluated anxiety responses based on the time spent in illuminated versus dark compartments. Trajectory body coordinates and tail kinematics were quantified using ZebraZoom software to asses locomotor metrics status. Cortisol levels were measured to assess HPA axis function. Antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), were quantified to evaluate oxidative stress.</p><p><strong>Results: </strong>The results revealed that zebrafish exposed to sucrose exhibited significant hyperglycemia (**p < 0.01) and behavioural changes compared to those on control. Specifically, in the NTT, the hyperglycemic group demonstrated heightened anxiety-like behaviour, spending more time at the bottom zone of the tank. In the light/dark test, male zebrafish showed increased anxiety by spending more time in the dark compartment. Hyperglycemic zebrafish showed a significant blunting of the cortisol response, indicating impaired stress regulation. Additionally, SOD activity was increased, while CAT activity was decreased, suggesting an imbalance in antioxidative defense mechanisms.</p><p><strong>Conclusion: </strong>The zebrafish system effectively models the negative impacts of sucrose-induced hyperglycemia, providing valuable insights into the stress mechanisms associated with type 2 diabetes. These findings demonstrate that hyperglycemia alters both endocrine stress response and antioxidant systems, potentially serving as biomarkers of systemic stress.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Diabetes-related complications, such as diabetic peripheral neuropathy (DPN) and chronic kidney disease (CKD), severely affect quality of life. Early detection is crucial. This study investigates ocular imaging parameters as potential biomarkers for these conditions using corneal confocal microscopy (CCM) and optical coherence tomography angiography (OCTA).
Methods: This cross-sectional study included 76 type 2 diabetes patients (139 eyes) from Fujian Medical University Union Hospital. Participants underwent CCM to assess corneal nerve fiber density (CNFD), branching density (CNBD), and nerve fiber length (CNFL). OCTA and OCT were used to evaluate macular and peripapillary retinal vascular densities (VD) and retinal nerve fiber layer (RNFL) thickness. Laboratory tests measured sural nerve conduction velocity (SSNCV), urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). DPN and CKD were categorized using Toronto consensus criteria and UACR thresholds, respectively. Statistical analyses included Spearman correlation and ROC curve evaluations.
Results: Significant reductions in CNFD, CNBD, and CNFL were observed in the DPN + group compared to DPN- (P < 0.001, P = 0.005, P < 0.001). Corneal nerve parameters correlated positively with SSNCV (r = 0.419-0.430, P < 0.001). ROC analysis demonstrated CNFD as the most sensitive marker for detecting DPN (AUC = 0.7179, 95% CI: 0.6328-0.8031). Retinal superficial VD in the superior macular region showed the highest diagnostic performance for CKD (AUC = 0.7140, 95% CI: 0.6057-0.8223), with significant correlations between retinal VD parameters and UACR.
Conclusions: Corneal nerve parameters measured by CCM and retinal vascular parameters assessed by OCTA are promising non-invasive biomarkers for early detection and monitoring of diabetic neuropathic and microvascular disorders.
{"title":"Non-invasive biomarkers for diabetic complications: insights from corneal and retinal imaging.","authors":"Meichun Xiao, Yunhan Chen, Xiaoxin Yan, Li Wang, Huiqin Cheng, Wenqu Chen","doi":"10.1007/s00592-025-02588-y","DOIUrl":"https://doi.org/10.1007/s00592-025-02588-y","url":null,"abstract":"<p><strong>Background: </strong>Diabetes-related complications, such as diabetic peripheral neuropathy (DPN) and chronic kidney disease (CKD), severely affect quality of life. Early detection is crucial. This study investigates ocular imaging parameters as potential biomarkers for these conditions using corneal confocal microscopy (CCM) and optical coherence tomography angiography (OCTA).</p><p><strong>Methods: </strong>This cross-sectional study included 76 type 2 diabetes patients (139 eyes) from Fujian Medical University Union Hospital. Participants underwent CCM to assess corneal nerve fiber density (CNFD), branching density (CNBD), and nerve fiber length (CNFL). OCTA and OCT were used to evaluate macular and peripapillary retinal vascular densities (VD) and retinal nerve fiber layer (RNFL) thickness. Laboratory tests measured sural nerve conduction velocity (SSNCV), urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). DPN and CKD were categorized using Toronto consensus criteria and UACR thresholds, respectively. Statistical analyses included Spearman correlation and ROC curve evaluations.</p><p><strong>Results: </strong>Significant reductions in CNFD, CNBD, and CNFL were observed in the DPN + group compared to DPN- (P < 0.001, P = 0.005, P < 0.001). Corneal nerve parameters correlated positively with SSNCV (r = 0.419-0.430, P < 0.001). ROC analysis demonstrated CNFD as the most sensitive marker for detecting DPN (AUC = 0.7179, 95% CI: 0.6328-0.8031). Retinal superficial VD in the superior macular region showed the highest diagnostic performance for CKD (AUC = 0.7140, 95% CI: 0.6057-0.8223), with significant correlations between retinal VD parameters and UACR.</p><p><strong>Conclusions: </strong>Corneal nerve parameters measured by CCM and retinal vascular parameters assessed by OCTA are promising non-invasive biomarkers for early detection and monitoring of diabetic neuropathic and microvascular disorders.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}