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Blood pressure effects of SGLT2 inhibitors in kidney transplant recipients: a systematic review and meta-analysis.5 days agoPost-transplant hypertension is common in kidney transplant recipients and contributes to cardiovascular risk and allograft dysfunction. Most available data come from studies where the primary indication for SGLT2 inhibitor use was post-transplant diabetes mellitus or cardiorenal protection, with blood pressure assessed as a secondary outcome.
To systematically evaluate the impact of SGLT2 inhibitors on blood pressure, metabolic and renal outcomes, and safety in kidney transplant recipients.
PubMed, Embase, and Scopus clinical trial registries were systematically searched from inception to October 20, 2025. Randomized controlled trials and observational studies were included. Primary outcomes were changes in systolic and diastolic blood pressure at 3, 6, and 12 months. Secondary outcomes included body weight, glycated hemoglobin (HbA1c), renal function, and adverse events.
Twelve studies comprising 1,292 participants were included. In controlled difference-in-differences analyses (5 studies), SGLT2 inhibitors showed no significant blood pressure reductions versus control at any time point. Exploratory single-arm analyses suggested within-group systolic blood pressure reductions at 3 and 6 months; however, these estimates are at high risk of bias and cannot establish treatment effect.
Exploratory single-arm analyses suggested modest short-term reductions in systolic blood pressure and suggested metabolic effects with an acceptable safety profile. However, controlled difference-in-differences analyses showed no significant blood pressure reductions versus control. Most available evidence derives from studies in which SGLT2 inhibitors were not initiated specifically for blood pressure control. Dedicated randomized controlled trials are required to determine their role in the management of post-transplant hypertension.DiabetesCare/Management -
Genetic risk score as a predictor of gestational diabetes in Central European Caucasians.5 days agoGestational diabetes mellitus (GDM) is a common complication of pregnancy associated with perinatal complications and increased future risk of T2DM. GDM has a polygenic background partly overlapping with T2DM, and using a genetic risk score (GRS) that captures complex genetics may improve early detection of individuals at risk. SNPs previously associated with T2DM in the Czech population (21 loci) have been examined in a study comprising Caucasian (i) pregnant women with GDM (N = 416), (ii) non-diabetic population controls (N = 1170) and (iii) T2DM patients (N = 359) to analyse (di)similarities of T2DM and GDM genetic architecture using both weighted (wGRS) and unweighted (uGRS) GRS constructed based on single locus analyses. Fourteen of 21 SNPs had no influence on the GDM development. The most significant SNPs associated with GDM were within the ARAP1 (rs1552224; OR, 95% CI 2.98, 2.18-4.08) and MNTR1B (rs10830963; OR, 95% CI 1.78, 1.41-2.24) genes. Both uGRS (P < 0.0001) and wGRS (P < 0.0001), comprising alleles of the seven most strongly associated variants, were associated with GDM, with wGRS being a better discriminator-AUC 0.669 vs. 0.628 (P < 0.001). Carriers of the population-derived Q5 of wGRS (in comparison with Q1) have a significantly increased risk of GDM with OR (95% CI) 6.8 (4.3-10.9); P < 1.10-6. The same scores derived from the ARAP1, NOTCH2, and MTNR1B genes discriminate between the GDM and T2DM groups (P < 0.0001). Identification of statistically significant association of the population-specific wGRS with GDM susceptibility supports its potential clinical utility for the risk stratification of pregnant women (beyond established non-genetic risk factors). Yet, the actual health care adoption of GRS in the near future is unlikely, since additional validation, regulatory and administrative steps, thorough economic analyses, ethical discussion, etc. are certainly required.DiabetesCare/Management
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Derivation and validation of a prediction model for long-term mortality in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: the PREDICT-ST-Elevation Myocardial Infarction score.5 days agoThere are limited prediction models of long-term mortality for patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Against this background, we aimed to derive and validate a predictive model for long-term mortality in patients with STEMI undergoing PCI.
A total of 23 086 patients from a STEMI network were included in the derivation cohort. Using time-to-event regression analysis, predictors of long-term mortality were identified and used to develop a score ranging from 0 to 206 points, with a score directly proportional to the probability of mortality. The predictive performance of this score was then validated in patients from the EXAMINATION-EXTEND study (n=1498) and Coronary Artery diSease Tracking registry (n=1112). An outcome-based cut-point optimisation analysis was performed to determine the best cut-off value in the derivation and validation cohorts.
The prediction model for long-term mortality in STEMI (PREDICT-STEMI) score comprised seven variables: age, diabetes mellitus, previous myocardial infarction, previous ischaemic stroke/transient ischaemic attack, haemodynamic status, three-vessel disease and mechanical circulatory support. The score showed a Concordance index for long-term mortality of 0.81 (95% CI 0.80 to 0.81) in the derivation and 0.81 (95% CI 0.78 to 0.84) and 0.84 (95% CI 0.81 to 0.87) in the validation cohorts, respectively. The optimal prediction model cut-off was 60 points; compared with those with a low score, patients with a high score had a sixfold increased risk of long-term mortality in both the derivation and validation cohorts.
The PREDICT-STEMI score is a simple tool for predicting long-term mortality and facilitating early risk stratification and inform clinical decision-making.DiabetesCare/Management -
Increasing Type 2 Diabetes Screening and Treatment Rates at a Community Clinic.5 days agoBackground: Although type 2 diabetes mellitus (T2DM) and prediabetes are widespread conditions affecting many people across the United States, they often remain undiagnosed due to the lack of screening processes in primary care. Underdiagnosis of these conditions can lead to disease progression and poor outcomes. Objective: A clinical practice change was implemented at a community clinic to improve screening rates and provide earlier patient treatment by implementing a systematic screening and treatment protocol into the current workflow. Methods: The existing clinic flow was adjusted to reflect updated screening guidelines by the American Diabetes Association. The clinic providers were trained on implementing this change and complied with the new process until project completion. Results: Descriptive statistics were used to analyze the collected data. The results were as follows: 32 patients were screened for diabetes, totaling a screening rate of 39.51%; in addition, 2.46% of patients were diagnosed with T2DM, and 4.96% were identified as prediabetic. As a result, 100% of the patients identified received standard-of-care treatment. Conclusions: This clinical practice change increased screening rates and impacted early identification and treatment of T2DM and prediabetes. The clinical facility will continue implementing this standard of care within its daily routine. Implications for Nursing: Systematic screening protocols positively impact screening rates and patient care.DiabetesDiabetes type 2Care/Management
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Late-Onset Diagnosis of Gestational Diabetes After Normal Mid-Pregnancy Screening in Women with Large for Gestational Age or Polyhydramnios: A Systematic Review and Meta-Analysis.5 days agoTo determine the detection rate of late-onset gestational diabetes mellitus (GDM) and associated perinatal outcomes in women with normal mid-pregnancy glucose screening who undergo repeat oral glucose tolerance testing (OGTT) due to suspected large-for-gestational-age (LGA) fetuses or polyhydramnios.
We systematically searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for studies published from January 2010 to November 2024.
We included cohort studies reporting late GDM detection rates in women with documented normal mid-pregnancy glucose testing (negative glucose challenge test or normal 75g OGTT at 24-28 weeks) who underwent repeat OGTT after 28 weeks due to sonographic findings of suspected LGA or polyhydramnios. We excluded studies of women with pre-existing diabetes, those lacking documented normal mid-pregnancy screening, and those examining routine late testing without specific clinical indication.
Study quality was assessed using the Newcastle-Ottawa Scale. Pooled detection rates with 95% confidence intervals were calculated using random-effects meta-analysis. Subgroup analyses were performed by clinical indication, timing of testing, initial screening method (two-step vs one-step), and maternal BMI. Perinatal outcomes were compared using pooled odds ratios calculated with the Mantel-Haenszel method.
Six cohort studies including 2,166 women met inclusion criteria. The pooled detection rate was 15.0% (95% CI: 9.9-21.0%; I2=91%). Detection rates varied significantly by indication: suspected LGA 20.8% (95% CI: 17.4-24.6%) vs. isolated polyhydramnios 4.8% (95% CI: 2.0-10.8%). Women with late-onset GDM had significantly higher rates of neonatal hypoglycemia (OR 1.82; 95% CI: 1.18-2.81), overall cesarean delivery (OR 2.00; 95% CI: 1.47-2.72), elective cesarean for LGA/macrosomia (OR 3.37; 95% CI: 2.01-5.64), emergent cesarean (OR 1.64; 95% CI: 1.05-2.57), and induction of labor (OR 2.27; 95% CI: 1.32-3.89). Macrosomia by birth weight and LGA at delivery were not significantly elevated.
Late OGTT detects GDM in approximately one in six women with normal mid-pregnancy screening who develop LGA or polyhydramnios. Late-onset GDM is associated with significantly increased neonatal hypoglycemia and cesarean delivery, with the largest effect for elective cesarean for suspected LGA/macrosomia. These findings may inform clinical decision-making regarding repeat glucose testing in the third trimester.DiabetesCare/Management -
Cardiovascular outcomes with thiazolidinediones and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus undergoing peripheral artery revascularization.5 days agoThe comparative effectiveness of anti-diabetic agents in patients with type 2 diabetes mellitus (T2DM) undergoing peripheral artery revascularization remains unclear.
Using the Korean National Health Insurance Claims database (2015-2023), we identified patients with T2DM who underwent peripheral artery revascularization (endovascular or surgical). To control for baseline differences, we utilized 1:3 propensity score matching to compare thiazolidinediones (TZD) vs. dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) vs. DPP-4i. Stratified Cox regression model assessed the risk for the primary outcome, defined as a composite of major adverse limb events (repeated revascularization or amputation), stroke, myocardial infarction, admission for heart failure, and all-cause death.
The primary outcome occurred in 49.2% of TZD users versus 55.5% of DPP-4i users (HR 0.74; 95% CI 0.63-0.86; p < 0.001) and in 39.7% of SGLT-2i users versus 52.2% of DPP-4i users (HR 0.88; 95% CI 0.79-0.98; p = 0.015). Regarding secondary outcomes, TZD users were associated with lower risks of major adverse limb events, and all-cause death compared with DPP-4i users. SGLT-2i treatment was associated with reduced all-cause death.
Among patients with T2DM undergoing peripheral artery revascularization, TZD and SGLT-2i were associated with favourable clinical outcomes compared to DPP-4i.DiabetesDiabetes type 2Care/Management -
Multi-modal sensor fusion in smart footwear to capture altered gait dynamics in patients with diabetic peripheral neuropathy: System validation and clinical applications.5 days agoIndividuals with diabetic peripheral neuropathy (DPN) are confronted with significantly elevated risk of falling and diabetic foot ulcers. There is an increasing need for clinically viable wearable technologies for routine biomechanical assessment of DPN patients.
Can a footwear-based wearable system ("Lab-in-Shoe") achieve gold-standard accuracy and effectively distinguish gait characteristics among patients with type 2 diabetes (T2DM) under various neuropathic conditions?
The spatiotemporal accuracy of the system was first validated against an 8-camera Vicon motion capture system using a single-marker strategy. For clinical evaluation, thirty T2DM patients were classified into G1 (no neuropathy), G2 (subclinical), and G3 (confirmed DPN). All patients performed a 10 m walking test, utilizing the "Lab-in-Shoe" to simultaneously capture spatiotemporal parameters and plantar pressure to evaluate their effectiveness in distinguishing degrees of neuropathy. Additionally, a Diabetic Gait Index (DGI) was formulated based on these fused features.
The system showed excellent agreement with Vicon across all seven evaluated spatiotemporal parameters, yielding mean absolute errors (MAE) between 2% and 8% and intraclass correlation coefficients (ICC) ranging from 0.812 to 0.993. The severe neuropathy group (G3) exhibited a 14% reduction in step length (p < 0.001) and a 14% reduction in step height (p < 0.01). Concurrently, step frequency was significantly increased by 8% (p < 0.001) and swing phase duration was shorter by 9% (p < 0.01). Regarding plantar loading, G3 showed significantly higher load under the second metatarsal and lateral heel compared to G1 (all p < 0.05). Furthermore, the proposed DGI achieved an 86.7% accuracy in classifying the three neuropathy severity groups.
This wearable system effectively detects subtle gait changes associated with the progression of DPN. It is well-suited for routine clinical practice, offering an objective tool for early risk screening for falls and ulceration in DPN patients.DiabetesCare/Management -
Self-Cascading Copper-Based Nanoassemblies Trigger Bacterial Cuproptosis-Like Death and Promote Wound Healing for Diabetic Drug-Resistant Bacterial Infections.5 days agoDiabetes mellitus leads to systemic immunosuppression, increasing susceptibility to persistent infections and elevating the risk of severe complications. Concurrently, multidrug-resistant (MDR) pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) further exacerbate therapeutic difficulties. To address this challenge, we engineered peroxidase (POD)-like nanoassemblies (DC/Cu) through the copper-coordinated self-assembly of ε-poly(L-lysine)-derived carbon dots (CDs) and anti-inflammatory agent diclofenac sodium (DS). These nanoassemblies integrate antibacterial, anti-inflammatory, and tissue-reparative functionalities for the treatment of MDR bacteria-induced diabetic infections. Cationic DC/Cu can selectively adhere to bacterial membranes, enabling microenvironment-responsive spatiotemporal drug release. The POD-like activity of CDs catalyzes the endogenous H2O2, inducing membrane lipid peroxidation and enhancing cell membrane permeability, which facilitates copper influx. This self-cascade induces lethal intracellular copper overload in MRSA, with transcriptomic profiling confirming Cu2+-mediated inhibition of Fe-S cluster proteins and disruption of the tricarboxylic acid cycle, leading to subsequent activation of cuproptosis-like death pathway. Simultaneously, the released DS mitigates the inflammatory response, while Cu2+ facilitates tissue regeneration. MRSA-infected diabetic foot ulcers and diabetic MRSA keratitis models validated DC/Cu's multifunctional efficacy in bacterial eradication, inflammatory mitigation, and tissue regeneration. Collectively, these multifunctional nanoassemblies demonstrate a promising and effective approach for precision therapeutic intervention against MDR pathogen-aggravated diabetic complications.DiabetesCare/Management
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Incidence and Associated Factors of ST-Segment Changes in Noncardiac Surgery Under General Anesthesia.5 days agoIntraoperative cardiac complications may result from an imbalance between myocardial oxygen supply and demand or from plaque rupture. Electrocardiographic (ECG) alterations in the ST-segment observed during surgery or anesthesia can serve as indicators of myocardial ischemia. Numerous factors influence ST-segment variability. This study aimed to investigate the incidence of ST-segment changes and the factors associated with their occurrence.
This prospective observational study enrolled adult patients (aged ≥ 20 years) undergoing noncardiac surgery under general anesthesia. Intraoperative ST-segment monitoring was performed using a five-electrode system. Predisposing factors for ischemia, including hemodynamic parameters, coexisting diseases, and surgical characteristics, were evaluated. A P-value of <0.05 was considered statistically significant.
A total of 102 patients were evaluated, with a mean age of 46.75 ± 16.30 years, comprising 46 males (45.1%). Postinduction ST-segment depression was greater than preinduction (-0.030 to - 0.055 vs. 0.010 to 0.060, respectively) (P = 0.0 01). ST-segment values were significantly more depressed in patients with underlying conditions, particularly hypertension and diabetes mellitus (P = 0.001). Also, the variations in ST-segment alteration were considerable among minor and major surgeries (P = 0.041). Overall, 20 patients (19.6%) exhibited prominent ST-segment changes (greater than 0.1 mV) during surgery; however, the changes were predominantly transient and managed successfully with initial clinical interventions (e.g., fluid administration). While postinduction blood pressure showed a significant drop, no statistical association was observed between the magnitude of blood pressure changes and the occurrence of ST-segment changes (P = 0.10). No significant relationship was identified between ST-segment changes and other evaluated factors.
The intraoperative ST-segment changes occurred following anesthetic induction and are significantly correlated with predisposing factors, specifically hypertension, diabetes mellitus, and major vs. minor surgeries. Despite significant hemodynamic alterations during the procedure, a direct correlation with prominent ST-segment changes could not be statistically established. Given the transient nature of most alterations, further studies incorporating postoperative troponin measurement and long-term follow-up are warranted to clarify the clinical significance of these intraoperative findings.DiabetesCare/Management -
Artemether ameliorates type 1 diabetic liver injury alongside the associated defects in mitochondrial ultrastructure and central carbon metabolism.5 days agoType 1 diabetes mellitus (T1DM) is characterized by autoimmune-mediated destruction of pancreatic islet β-cells and the resultant absolute insulin deficiency, which leads to systemic metabolic dysregulation. Hepatic injury has emerged as a clinically significant complication of T1DM; however, no targeted therapeutic intervention is currently available. Artemether (Art), a methyl ether derivative of artemisinin, has shown potential in ameliorating hyperglycemia, but its efficacy in mitigating T1DM-associated hepatic dysfunction remains insufficiently elucidated. This study comprehensively evaluates the hepatoprotective effects of Art in a murine model of T1DM, with particular emphasis on mitochondrial structural integrity and the regulation of glucose and lipid metabolism. Hepatic function was assessed through histopathological evaluation, ultrastructural examination of mitochondria via transmission electron microscopy, and molecular analysis of gene and protein expression levels. Metabolic intermediates associated with glucose and lipid metabolic pathways were quantitatively analyzed using ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS). Administration of Art significantly attenuated both diabetic manifestations and liver injury. Importantly, Art preserved mitochondrial morphology, restored the expression of some proteins related to the respiratory chain complex, and downregulated indicators of hepatic fatty acid β-oxidation, upregulated markers of de novo fatty acid synthesis, normalized intrahepatic triglyceride concentrations, and reduced expression of key molecules involved in gluconeogenesis and glycogenolysis. These findings indicate that Art confers protective effects against liver injury in T1DM through coordinated modulation of mitochondrial function and key metabolic pathways at transcriptional, translational, and metabolic intermediate levels.DiabetesDiabetes type 1Care/ManagementPolicy