Pub Date : 2025-12-22DOI: 10.1016/j.diabres.2025.113059
Hongmei Li, Xu Li, Fangjiu Liu
Background: Metformin reduces mortality in type 2 diabetes mellitus (T2DM), but its underlying pathways remain incompletely understood. We hypothesize that serum albumin could potentially mediate the effects of metformin on mortality. Methods: Participants were drawn from the National Health and Nutrition Examination Survey (NHANES) across ten cycles for this retrospective longitudinal analysis. We employed mediation analysis to assess the impact of metformin on all-cause mortality risk mediated by albumin (ALB). Results: In our longitudinal study, all-cause mortality was 40.97 %. Multivariate logistic regression analysis identified a significant correlation between metformin and the likelihood of all-cause mortality (HR = 0.8, 95 %CI = 0.71–0.90, P < 0.001). Mediation analysis indicated that the relationship between metformin and all-cause mortality risk was partially mediated by ALB, accounting for 13.32 % of the association (P < 0.0001). Conclusion: ALB mediates the association between metformin use and lower all-cause mortality in older Americans with T2DM and hypertension, underscoring the mortality-reducing importance of nutritional status.
{"title":"Metformin and all-cause mortality in older adults with type 2 diabetes mellitus and hypertension: NHANES 1999–2018 evidence for albumin as a mediator","authors":"Hongmei Li, Xu Li, Fangjiu Liu","doi":"10.1016/j.diabres.2025.113059","DOIUrl":"10.1016/j.diabres.2025.113059","url":null,"abstract":"<div><div><strong>Background:</strong> Metformin reduces mortality in type 2 diabetes mellitus (T2DM), but its underlying pathways remain incompletely understood. We hypothesize that serum albumin could potentially mediate the effects of metformin on mortality. <strong>Methods:</strong> Participants were drawn from the National Health and Nutrition Examination Survey (NHANES) across ten cycles for this retrospective longitudinal analysis. We employed mediation analysis to assess the impact of metformin on all-cause mortality risk mediated by albumin (ALB). <strong>Results:</strong> In our longitudinal study, all-cause mortality was 40.97 %. Multivariate logistic regression analysis identified a significant correlation between metformin and the likelihood of all-cause mortality (HR = 0.8, 95 %CI = 0.71–0.90, P < 0.001). Mediation analysis indicated that the relationship between metformin and all-cause mortality risk was partially mediated by ALB, accounting for 13.32 % of the association (P < 0.0001). <strong>Conclusion:</strong> ALB mediates the association between metformin use and lower all-cause mortality in older Americans with T2DM and hypertension, underscoring the mortality-reducing importance of nutritional status.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113059"},"PeriodicalIF":7.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827086","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 : 2025-12-22DOI: 10.1016/j.diabres.2025.113071
Nan Li, Hongmei Yu, Harvest F Gu
Recent single-cell sequencing analyses confirm that solute carriers (SLCs) are highly expressed in renal tubular epithelial cells, where they are critical for maintaining systemic metabolic homeostasis through solute reabsorption, secretion, and detoxification. SLC dysfunction underpins renal disorders, including chronic kidney disease, diabetic kidney disease, and acute kidney injury. Recent advances in SLC biology have enabled the development of selective inhibitors, offering precise pathway modulation with minimal off-target effects. Clinically, SLC inhibitors have demonstrated efficacy in nephrology, with five SLCs emerging as validated therapeutic targets: SLC5A2 (Na+-glucose co-transporter 2), SLC7A11 (xCT cystine/glutamate antiporter), SLC12A3 (Na+-Cl- co-transporter), SLC22A12 (urate transporter 1), and SLC47A1 (multidrug and toxin extrusion protein 1). This article systematically reviews the pharmacological mechanisms of SLC inhibitors targeting these five transporters, analyzing their physiological and pathological roles in kidney diseases, and further discusses clinical applications and future prospects of SLC-targeted therapies in nephrology.
{"title":"Solute carrier inhibitors in kidney disease therapy: mechanisms and clinical implications.","authors":"Nan Li, Hongmei Yu, Harvest F Gu","doi":"10.1016/j.diabres.2025.113071","DOIUrl":"https://doi.org/10.1016/j.diabres.2025.113071","url":null,"abstract":"<p><p>Recent single-cell sequencing analyses confirm that solute carriers (SLCs) are highly expressed in renal tubular epithelial cells, where they are critical for maintaining systemic metabolic homeostasis through solute reabsorption, secretion, and detoxification. SLC dysfunction underpins renal disorders, including chronic kidney disease, diabetic kidney disease, and acute kidney injury. Recent advances in SLC biology have enabled the development of selective inhibitors, offering precise pathway modulation with minimal off-target effects. Clinically, SLC inhibitors have demonstrated efficacy in nephrology, with five SLCs emerging as validated therapeutic targets: SLC5A2 (Na<sup>+</sup>-glucose co-transporter 2), SLC7A11 (xCT cystine/glutamate antiporter), SLC12A3 (Na<sup>+</sup>-Cl<sup>-</sup> co-transporter), SLC22A12 (urate transporter 1), and SLC47A1 (multidrug and toxin extrusion protein 1). This article systematically reviews the pharmacological mechanisms of SLC inhibitors targeting these five transporters, analyzing their physiological and pathological roles in kidney diseases, and further discusses clinical applications and future prospects of SLC-targeted therapies in nephrology.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113071"},"PeriodicalIF":7.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827130","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 : 2025-12-22DOI: 10.1016/j.diabres.2025.113065
Carolina Martinez-Mateu , Regina Duperval , Olga Kaminska-Jackowiak , Dalia Al-Abdulrazzaq , Suzanne Sap , Sunil Gupta , Marija Požgaj Šepec , Catherine Sanon , Rasha Thabet , Silvia Muñoz , Reinhard W. Holl , Danièle Pacaud , on behalf of the SWEET Study Group
Significant disparities in pediatric type 1 diabetes (T1D) care and outcomes exist globally.
Aim
To examine the relationship between national gross domestic product (GDP), diabetes care, and T1D outcomes.
Methods
Cross-sectional analysis of individuals < 25 years with T1D > 3 months from SWEET registry centers (2022–2023). Centers were grouped into GDP quartiles. Outcomes included technology use, screening rates, HbA1c, BMI SDS, diabetic ketoacidosis (DKA), and severe hypoglycemia. Multivariable regression adjusted for age, sex, and diabetes duration.
Results
Data from 54,285 individuals across 130 centers were analyzed. Technology use and BMI SDS increased with GDP. Insulin pump use ranged 17.4–70.2 %; CGM 36.2–91.5 %; AID 11.2–38.2 %; and rapid-acting analogs 56.9–78.2 %. BMI SDS ranged from + 0.04 (lowest GDP) to + 0.89 (highest). HbA1c showed a non-linear pattern: 8.74 % (lowest), 7.50 % (lower-middle), 7.66 % (higher-middle), 8.18 % (highest). Severe hypoglycemia ranged from 9.6 to 1.3 events/100 PY, while DKA ranged from 0.90 (lower-middle) to 3.10 events/100 PY (highest). Screening rates for comorbidities peaked in middle GDP quartiles.
Conclusions
GDP is significantly, but not linearly, associated with technology use and metabolic outcomes in pediatric T1D. Middle GDP countries achieved the best metabolic control, underscoring the need for equitable resource allocation.
{"title":"Comparison of demographics and treatment outcome in children with type 1 diabetes related to the economic background of their country of residence: observations from the SWEET database","authors":"Carolina Martinez-Mateu , Regina Duperval , Olga Kaminska-Jackowiak , Dalia Al-Abdulrazzaq , Suzanne Sap , Sunil Gupta , Marija Požgaj Šepec , Catherine Sanon , Rasha Thabet , Silvia Muñoz , Reinhard W. Holl , Danièle Pacaud , on behalf of the SWEET Study Group","doi":"10.1016/j.diabres.2025.113065","DOIUrl":"10.1016/j.diabres.2025.113065","url":null,"abstract":"<div><div>Significant disparities in pediatric type 1 diabetes (T1D) care and outcomes exist globally.</div></div><div><h3>Aim</h3><div>To examine the relationship between national gross domestic product (GDP), diabetes care, and T1D outcomes.</div></div><div><h3>Methods</h3><div>Cross-sectional analysis of individuals < 25 years with T1D > 3 months from SWEET registry centers (2022–2023). Centers were grouped into GDP quartiles. Outcomes included technology use, screening rates, HbA1c, BMI SDS, diabetic ketoacidosis (DKA), and severe hypoglycemia. Multivariable regression adjusted for age, sex, and diabetes duration.</div></div><div><h3>Results</h3><div>Data from 54,285 individuals across 130 centers were analyzed. Technology use and BMI SDS increased with GDP. Insulin pump use ranged 17.4–70.2 %; CGM 36.2–91.5 %; AID 11.2–38.2 %; and rapid-acting analogs 56.9–78.2 %. BMI SDS ranged from + 0.04 (lowest GDP) to + 0.89 (highest). HbA1c showed a non-linear pattern: 8.74 % (lowest), 7.50 % (lower-middle), 7.66 % (higher-middle), 8.18 % (highest). Severe hypoglycemia ranged from 9.6 to 1.3 events/100 PY, while DKA ranged from 0.90 (lower-middle) to 3.10 events/100 PY (highest). Screening rates for comorbidities peaked in middle GDP quartiles.</div></div><div><h3>Conclusions</h3><div>GDP is significantly, but not linearly, associated with technology use and metabolic outcomes in pediatric T1D. Middle GDP countries achieved the best metabolic control, underscoring the need for equitable resource allocation.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113065"},"PeriodicalIF":7.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827125","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 : 2025-12-21DOI: 10.1016/j.diabres.2025.113064
Shan Yin , Shuang Yan , Zhenzhen Yang , Pingyu Zhu , Tielong Tang , Yan Borné
Aims
This study compares the associations of Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8) with all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic (CKM) syndrome populations.
Methods
This cohort study analyzed 11,487 participants aged ≥20 years with CKM syndrome from NHANES 2005–2018. Participants were categorized into non-advanced (stages 0–2) and advanced (stages 3–4) CKM stages. LS7 and LE8 scores were calculated, and Cox proportional hazards models were used to assess mortality associations. Time-dependent ROC analysis compared LS7 and LE8’s predictive performance.
Results
During a median follow-up of 91 months, 1167 all-cause deaths and 360 cardiovascular deaths occurred. Both LS7 and LE8 showed strong negative associations with mortality. In fully adjusted models for the entire CKM population, high versus low CVH groups demonstrated significant risk reductions: LE8 (HR 0.63 for all-cause; HR 0.53 for cardiovascular mortality) and LS7 (HR 0.69; HR 0.59). Similar protective associations were observed in non-advanced CKM stages but not in advanced stages. Both metrics had comparable predictive ability with similar AUC values.
Conclusion
LS7 and LE8 demonstrate comparable predictive ability for mortality outcomes in CKM syndrome, particularly in non-advanced stages. LS7’s simplicity makes it favorable for clinical and public health practice.
{"title":"Association between Life’s Simple 7 and life’s essential 8 with all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic syndrome population","authors":"Shan Yin , Shuang Yan , Zhenzhen Yang , Pingyu Zhu , Tielong Tang , Yan Borné","doi":"10.1016/j.diabres.2025.113064","DOIUrl":"10.1016/j.diabres.2025.113064","url":null,"abstract":"<div><h3>Aims</h3><div>This study compares the associations of Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8) with all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic (CKM) syndrome populations.</div></div><div><h3>Methods</h3><div>This cohort study analyzed 11,487 participants aged ≥20 years with CKM syndrome from NHANES 2005–2018. Participants were categorized into non-advanced (stages 0–2) and advanced (stages 3–4) CKM stages. LS7 and LE8 scores were calculated, and Cox proportional hazards models were used to assess mortality associations. Time-dependent ROC analysis compared LS7 and LE8’s predictive performance.</div></div><div><h3>Results</h3><div>During a median follow-up of 91 months, 1167 all-cause deaths and 360 cardiovascular deaths occurred. Both LS7 and LE8 showed strong negative associations with mortality. In fully adjusted models for the entire CKM population, high versus low CVH groups demonstrated significant risk reductions: LE8 (HR 0.63 for all-cause; HR 0.53 for cardiovascular mortality) and LS7 (HR 0.69; HR 0.59). Similar protective associations were observed in non-advanced CKM stages but not in advanced stages. Both metrics had comparable predictive ability with similar AUC values.</div></div><div><h3>Conclusion</h3><div>LS7 and LE8 demonstrate comparable predictive ability for mortality outcomes in CKM syndrome, particularly in non-advanced stages. LS7’s simplicity makes it favorable for clinical and public health practice.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113064"},"PeriodicalIF":7.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818139","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 : 2025-12-21DOI: 10.1016/j.diabres.2025.113069
Thyago Bruno de Lira dos Santos , Giselle Rabelo Maciel , Francisco Bandeira
Aims
To evaluate the diagnostic performance of a consumer-grade bioelectrical impedance analyzer (OMRON HBF-514C) against dual-energy X-ray absorptiometry (DXA) for detecting sarcopenia in women with type 2 diabetes (T2DM).
Methods
In this cross‑sectional study, 103 women with T2DM underwent body composition assessment using the OMRON HBF‑514C BIA device and DXA. Sarcopenia was defined by fat‑free mass index (FFMI), skeletal muscle index (SMI), and established DXA‑based criteria. Analyses included Spearman correlation, Bland–Altman plots, Cohen’s kappa, receiver operating characteristic curves, and regression‑based bias correction.
Results
FFMI-BIA strongly correlated with FFMI-DXA (r = 0.881) and with SMI (r = 0.854). ROC analyses yielded AUCs of 0.878 and 0.873 with optimized FFMI-BIA cut-offs, giving sensitivity/specificity of 87.8 %/79.3 % and 85.1 %/82.8 %, respectively. The bias-correction model explained 78.3 % of the variance in FFMI-DXA and reduced mean bias to −0.0009 kg/m2 (limits of agreement −2.07 to 2.07 kg/m2). Prevalence estimates and moderate agreement supported performance (κ = 0.575).
Conclusions
The OMRON HBF‑514C shows strong correlation, accurate diagnostic performance with optimized cut‑offs, and minimal systematic bias after calibration. Its affordability, portability, and enhanced precision support its use for sarcopenia screening in resource‑limited settings when combined with functional assessments.
{"title":"Can a consumer-grade bioimpedance device accurately estimate sarcopenia in women with type 2 diabetes? A cross-sectional agreement study with dual-energy X-ray absorptiometry","authors":"Thyago Bruno de Lira dos Santos , Giselle Rabelo Maciel , Francisco Bandeira","doi":"10.1016/j.diabres.2025.113069","DOIUrl":"10.1016/j.diabres.2025.113069","url":null,"abstract":"<div><h3>Aims</h3><div>To evaluate the diagnostic performance of a consumer-grade bioelectrical impedance analyzer (OMRON HBF-514C) against dual-energy X-ray absorptiometry (DXA) for detecting sarcopenia in women with type 2 diabetes (T2DM).</div></div><div><h3>Methods</h3><div>In this cross‑sectional study, 103 women with T2DM underwent body composition assessment using the OMRON HBF‑514C BIA device and DXA. Sarcopenia was defined by fat‑free mass index (FFMI), skeletal muscle index (SMI), and established DXA‑based criteria. Analyses included Spearman correlation, Bland–Altman plots, Cohen’s kappa, receiver operating characteristic curves, and regression‑based bias correction.</div></div><div><h3>Results</h3><div>FFMI-BIA strongly correlated with FFMI-DXA (r = 0.881) and with SMI (r = 0.854). ROC analyses yielded AUCs of 0.878 and 0.873 with optimized FFMI-BIA cut-offs, giving sensitivity/specificity of 87.8 %/79.3 % and 85.1 %/82.8 %, respectively. The bias-correction model explained 78.3 % of the variance in FFMI-DXA and reduced mean bias to −0.0009 kg/m<sup>2</sup> (limits of agreement −2.07 to 2.07 kg/m<sup>2</sup>). Prevalence estimates and moderate agreement supported performance (κ = 0.575).</div></div><div><h3>Conclusions</h3><div>The OMRON HBF‑514C shows strong correlation, accurate diagnostic performance with optimized cut‑offs, and minimal systematic bias after calibration. Its affordability, portability, and enhanced precision support its use for sarcopenia screening in resource‑limited settings when combined with functional assessments.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113069"},"PeriodicalIF":7.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818137","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 : 2025-12-21DOI: 10.1016/j.diabres.2025.113066
Ebaa Al Ozairi , Etab Taghadom , Mohammad Irshad , Anas Al Yousef , Jumana AlKandari , Werd Al-Najim , Shahd Alabdulkader , Alexander D Miras , Carel W. le Roux
Aims
We investigated the safety and efficacy of combining glucagon-like peptide-1 (GLP-1) analogues with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 1 diabetes, BMI > 25 kg/m2, and early chronic kidney disease.
Methods
This single-centre pilot study (NCT05390307) randomised 60 participants to usual care, GLP-1, SGLT2i, GLP-1 + SGLT2i, or GLP-1 + SGLT2i + lifestyle modification for 6 months. The primary endpoint was change in bodyweight. Secondary endpoints included markers of kidney disease, glycaemic, blood pressure, and lipids. Analyses were performed using both intention-to-treat and per-protocol approaches.
Results
In the intention-to-treat analysis, the GLP-1 + SGLT2i + lifestyle group achieved significantly greater bodyweight loss than usual care [-9·6%, (95 %CI −14·4, −4·9), p < 0.001], and SGLT2i alone [-8·0 (95 %CI −12·6, −3·4), p = 0·002]. No significant differences in glycaemia or blood pressure were observed among groups. However, the GLP-1 + SGLT2i + lifestyle showed a reduction in urine albumin creatinine ratio from 784·9mg/g (95 %CI 500·7, 1069·1) to 287·6mg/g (95 %CI −1·6, 576·8), p < 0·001). Adverse events occurred in 50% of participants in both the usual care (n = 6/12) and medication groups (n = 24/48).
Conclusions
In patients with type 1 diabetes, BMI > 25 kg/m2, and chronic kidney disease, the combining GLP-1 + SGLT2i + lifestyle modification was safe and produced significant weight loss but did not significantly improve metabolic and blood pressure control.
{"title":"Combining glucagon-like peptide 1 analogues with sodium-glucose cotransporter 2 inhibitors to treat patients with type 1 diabetes, BMI > 25 kg/m2, and chronic kidney disease – A randomised, controlled pilot study","authors":"Ebaa Al Ozairi , Etab Taghadom , Mohammad Irshad , Anas Al Yousef , Jumana AlKandari , Werd Al-Najim , Shahd Alabdulkader , Alexander D Miras , Carel W. le Roux","doi":"10.1016/j.diabres.2025.113066","DOIUrl":"10.1016/j.diabres.2025.113066","url":null,"abstract":"<div><h3>Aims</h3><div>We investigated the safety and efficacy of combining glucagon-like peptide-1 (GLP-1) analogues with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 1 diabetes, BMI > 25 kg/m<sup>2</sup>, and early chronic kidney disease.</div></div><div><h3>Methods</h3><div>This <strong>s</strong>ingle-centre pilot study (NCT05390307) randomised 60 participants to usual care, GLP-1, SGLT2i, GLP-1 + SGLT2i, or GLP-1 + SGLT2i + lifestyle modification for 6 months. The primary endpoint was change in bodyweight. Secondary endpoints included markers of kidney disease, glycaemic, blood pressure, and lipids. Analyses were performed using both intention-to-treat and per-protocol approaches.</div></div><div><h3>Results</h3><div>In the intention-to-treat analysis, the GLP-1 + SGLT2i + lifestyle group achieved significantly greater bodyweight loss than usual care [-9·6%, (95 %CI −14·4, −4·9), p < 0.001], and SGLT2i alone [-8·0 (95 %CI −12·6, −3·4), p = 0·002]. No significant differences in glycaemia or blood pressure were observed among groups. However, the GLP-1 + SGLT2i + lifestyle showed a reduction in urine albumin creatinine ratio from 784·9mg/g (95 %CI 500·7, 1069·1) to 287·6mg/g (95 %CI −1·6, 576·8), p < 0·001). Adverse events occurred in 50% of participants in both the usual care (n = 6/12) and medication groups (n = 24/48).</div></div><div><h3>Conclusions</h3><div>In patients with type 1 diabetes, BMI > 25 kg/m<sup>2</sup>, and chronic kidney disease, the combining GLP-1 + SGLT2i + lifestyle modification was safe and produced significant weight loss but did not significantly improve metabolic and blood pressure control.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113066"},"PeriodicalIF":7.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818118","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 : 2025-12-21DOI: 10.1016/j.diabres.2025.113070
Yueyun Zhu , Alberto Alvarez-Iglesias , Aoife M. Egan , Andrew Smyth , Christine Newman , David Aguilar Macias , Declan Devane , Fidelma Dunne , Martin O’Donnell , Paula O’Shea , Paddy Gillespie , Andrew J. Simpkin
Aims
Gestational diabetes mellitus (GDM) is a global health problem. Insulin therapy is recommended when lifestyle management fails to control blood glucose. We aim to predict the time to insulin initiation for women with GDM.
Methods
A random survival forest (RSF) model was developed to predict the time to insulin initiation among 413 women from the EMERGE trial, analysed separately for placebo and metformin groups. Maternal characteristics and early glucose data (collected during the two weeks after randomisation) were used as predictors. Decision curve analysis was performed to assess the net benefit of the model compared with default strategies.
Results
The RSF model had a concordance index (C-index) of 0.71 (95 % CI: 0.64–0.77), time-dependent AUC ≥0.70 and Brier score ≤0.2 for the placebo group, and a C-index of 0.72 (95 % CI: 0.64–0.80), time-dependent AUC ≥0.75 and Brier score ≤0.2 for the metformin group. The decision curve analysis showed the RSF provided a higher net benefit for both groups compared to default strategies across clinically relevant threshold probabilities.
Conclusions
The RSF model effectively identified women at high risk of requiring insulin. The decision curve analysis could help clinicians to balance insulin initiation decisions. However, prospective validation is needed to confirm the generalisability of the model.
{"title":"Prediction of time to insulin initiation in gestational diabetes mellitus: a secondary analysis of the EMERGE trial","authors":"Yueyun Zhu , Alberto Alvarez-Iglesias , Aoife M. Egan , Andrew Smyth , Christine Newman , David Aguilar Macias , Declan Devane , Fidelma Dunne , Martin O’Donnell , Paula O’Shea , Paddy Gillespie , Andrew J. Simpkin","doi":"10.1016/j.diabres.2025.113070","DOIUrl":"10.1016/j.diabres.2025.113070","url":null,"abstract":"<div><h3>Aims</h3><div>Gestational diabetes mellitus (GDM) is a global health problem. Insulin therapy is recommended when lifestyle management fails to control blood glucose. We aim to predict the time to insulin initiation for women with GDM.</div></div><div><h3>Methods</h3><div>A random survival forest (RSF) model was developed to predict the time to insulin initiation among 413 women from the EMERGE trial, analysed separately for placebo and metformin groups. Maternal characteristics and early glucose data (collected during the two weeks after randomisation) were used as predictors. Decision curve analysis was performed to assess the net benefit of the model compared with default strategies.</div></div><div><h3>Results</h3><div>The RSF model had a concordance index (C-index) of 0.71 (95 % CI: 0.64–0.77), time-dependent AUC ≥0.70 and Brier score ≤0.2 for the placebo group, and a C-index of 0.72 (95 % CI: 0.64–0.80), time-dependent AUC ≥0.75 and Brier score ≤0.2 for the metformin group. The decision curve analysis showed the RSF provided a higher net benefit for both groups compared to default strategies across clinically relevant threshold probabilities.</div></div><div><h3>Conclusions</h3><div>The RSF model effectively identified women at high risk of requiring insulin. The decision curve analysis could help clinicians to balance insulin initiation decisions. However, prospective validation is needed to confirm the generalisability of the model.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113070"},"PeriodicalIF":7.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818209","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 : 2025-12-20DOI: 10.1016/j.diabres.2025.113063
Jennifer A Andersen, Pearl A McElfish, James P Selig, Ji Li, Brett Rowland, Jonell Hudson, Shashank Kraleti, Joseph Henske, Lindsay S Mayberry
Aims: Family members/support persons can shape the self-management decisions of persons with T2DM (PWDs), and their inclusion in DSMES may lead to improved outcomes. However, research on the effectiveness of family models of DSMES (Family-DSMES) is limited. We conducted a comparative effectiveness-implementation RCT of Family-DSMES and a standard model of DSMES (Standard-DSMES) delivered via telehealth.
Methods: 550 diverse adult PWDs and their family members/support persons were recruited from eight primary care clinics in both rural and urban areas. Process data was collected to evaluate implementation characteristics. Biometric, behavioral, and psychosocial measures were collected from PWD.
Results: Mean attendance was slightly higher for PWDs in Family-DSMES than Standard-DSMES (62 % vs. 57 %, p = 0.096). Engagement (p = 0.319) and class time (p = 0.145) were similar across arms. PWDs in both arms experienced a decrease in HbA1c at all time points (p < 0.005). No statistically significant between-arm differences were found for biometric outcomes or behavioral outcomes including HbA1c. For diabetes-related helpful family involvement, the improvement in the Family-DSMES arm was significantly greater than in the Standard-DSMES arm (p = 0.024).
Conclusions: Results demonstrate the ability to engage rural and diverse PWDs in a telehealth intervention with high fidelity to achieve clinically and statistically significant improvements in HbA1c.
{"title":"Comparative effectiveness of telehealth-delivered family and standard models of diabetes self-management education and support for persons with type 2 diabetes mellitus.","authors":"Jennifer A Andersen, Pearl A McElfish, James P Selig, Ji Li, Brett Rowland, Jonell Hudson, Shashank Kraleti, Joseph Henske, Lindsay S Mayberry","doi":"10.1016/j.diabres.2025.113063","DOIUrl":"https://doi.org/10.1016/j.diabres.2025.113063","url":null,"abstract":"<p><strong>Aims: </strong>Family members/support persons can shape the self-management decisions of persons with T2DM (PWDs), and their inclusion in DSMES may lead to improved outcomes. However, research on the effectiveness of family models of DSMES (Family-DSMES) is limited. We conducted a comparative effectiveness-implementation RCT of Family-DSMES and a standard model of DSMES (Standard-DSMES) delivered via telehealth.</p><p><strong>Methods: </strong>550 diverse adult PWDs and their family members/support persons were recruited from eight primary care clinics in both rural and urban areas. Process data was collected to evaluate implementation characteristics. Biometric, behavioral, and psychosocial measures were collected from PWD.</p><p><strong>Results: </strong>Mean attendance was slightly higher for PWDs in Family-DSMES than Standard-DSMES (62 % vs. 57 %, p = 0.096). Engagement (p = 0.319) and class time (p = 0.145) were similar across arms. PWDs in both arms experienced a decrease in HbA1c at all time points (p < 0.005). No statistically significant between-arm differences were found for biometric outcomes or behavioral outcomes including HbA1c. For diabetes-related helpful family involvement, the improvement in the Family-DSMES arm was significantly greater than in the Standard-DSMES arm (p = 0.024).</p><p><strong>Conclusions: </strong>Results demonstrate the ability to engage rural and diverse PWDs in a telehealth intervention with high fidelity to achieve clinically and statistically significant improvements in HbA1c.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113063"},"PeriodicalIF":7.4,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809598","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 retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, characterized by both microvascular damage and neurodegeneration. Despite advances in clinical management, current treatment options remain limited and lack effective therapeutic targets. Recent evidence has revealed that ferroptosis—an iron-dependent form of programmed cell death—plays a crucial role in the onset and progression of DR. Ferroptosis exacerbates DR pathology by disrupting the homeostasis of retinal vascular and neuronal systems. Moreover, accumulating studies have demonstrated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), can modulate ferroptosis in DR through direct or indirect regulation of ferroptosis-related proteins and their downstream pathways. Elucidating the molecular mechanisms of ferroptosis regulators and the ncRNAs involved in this process may therefore uncover novel therapeutic strategies and intervention targets for DR. This review systematically summarizes recent advances in understanding the regulatory roles of ncRNAs in ferroptosis during DR progression and discusses future research directions in this emerging field.
{"title":"Regulatory roles of non-coding RNAs in ferroptosis during diabetic retinopathy","authors":"Qingjun Tian , Chenxing Guo , Fang Yuan , Ying Shao , Xing Liang , Hetian Lei , JingJing Wang , Ronghua Feng , Yajian Duan","doi":"10.1016/j.diabres.2025.113062","DOIUrl":"10.1016/j.diabres.2025.113062","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, characterized by both microvascular damage and neurodegeneration. Despite advances in clinical management, current treatment options remain limited and lack effective therapeutic targets. Recent evidence has revealed that ferroptosis—an iron-dependent form of programmed cell death—plays a crucial role in the onset and progression of DR. Ferroptosis exacerbates DR pathology by disrupting the homeostasis of retinal vascular and neuronal systems. Moreover, accumulating studies have demonstrated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), can modulate ferroptosis in DR through direct or indirect regulation of ferroptosis-related proteins and their downstream pathways. Elucidating the molecular mechanisms of ferroptosis regulators and the ncRNAs involved in this process may therefore uncover novel therapeutic strategies and intervention targets for DR. This review systematically summarizes recent advances in understanding the regulatory roles of ncRNAs in ferroptosis during DR progression and discusses future research directions in this emerging field.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113062"},"PeriodicalIF":7.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786737","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 : 2025-12-18DOI: 10.1016/j.diabres.2025.113061
Xuhong Wang , Ye Hu , Chengyong Tang , Chenghu Huang , Fengxue Guo , Wei Chen
Aims
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of GZR4 in patients with type 2 diabetes mellitus (T2DM).
Methods
This randomized, active-controlled, phase 1b trial was conducted in adults with T2DM on stable daily basal insulin therapy. Eligible participants were randomized in 3:1 ratio within three cohorts to receive either a fixed once-weekly dose of GZR4 or once-daily insulin degludec (IDeg) subcutaneously for six weeks. Primary endpoints were incidence of adverse events (AEs), serious adverse events (SAEs), and hypoglycemia.
Results
The most commonly reported treatment-emergent AE across all treatment groups was hypoglycemia. No SAEs or severe hypoglycemia was observed. At steady state, the mean Cmax of GZR4 was 289.0 ± 17.1 to 1,016.0 ± 262.4 ng/mL; mean AUCGZR4, 0-168h ranged from 34,449.6 ± 2,055.7 to 137,064.2 ± 41,496.5 h.ng/mL. Mean change in FPG from baseline to week 6 was −1.77 ± 0.20 to −2.75 ± 0.71 mmol/L for GZR4 groups and −1.12 ± 0.36 mmol/L for IDeg group; corresponding change in HbA1c was −0.38 ± 0.64 % to −0.76 ± 0.14 % versus −0.13 ± 0.21 %.
Conclusions
GZR4 was safe and well tolerated in patients with diabetes in present trial with pharmacokinetic and pharmacodynamic profiles enabling once-weekly dosing.
{"title":"A phase 1b, randomized, open-label study of once-weekly insulin GZR4 in patients with type 2 diabetes mellitus","authors":"Xuhong Wang , Ye Hu , Chengyong Tang , Chenghu Huang , Fengxue Guo , Wei Chen","doi":"10.1016/j.diabres.2025.113061","DOIUrl":"10.1016/j.diabres.2025.113061","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of GZR4 in patients with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>This randomized, active-controlled, phase 1b trial was conducted in adults with T2DM on stable daily basal insulin therapy. Eligible participants were randomized in 3:1 ratio within three cohorts to receive either a fixed once-weekly dose of GZR4 or once-daily insulin degludec (IDeg) subcutaneously for six weeks. Primary endpoints were incidence of adverse events (AEs), serious adverse events (SAEs), and hypoglycemia.</div></div><div><h3>Results</h3><div>The most commonly reported treatment-emergent AE across all treatment groups was hypoglycemia. No SAEs or severe hypoglycemia was observed. At steady state, the mean C<sub>max</sub> of GZR4 was 289.0 ± 17.1 to 1,016.0 ± 262.4 ng/mL; mean AUC<sub>GZR4, 0-168h</sub> ranged from 34,449.6 ± 2,055.7 to 137,064.2 ± 41,496.5 h.ng/mL. Mean change in FPG from baseline to week 6 was −1.77 ± 0.20 to −2.75 ± 0.71 mmol/L for GZR4 groups and −1.12 ± 0.36 mmol/L for IDeg group; corresponding change in HbA1c was −0.38 ± 0.64 % to −0.76 ± 0.14 % versus −0.13 ± 0.21 %.</div></div><div><h3>Conclusions</h3><div>GZR4 was safe and well tolerated in patients with diabetes in present trial with pharmacokinetic and pharmacodynamic profiles enabling once-weekly dosing.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113061"},"PeriodicalIF":7.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800415","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}
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